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36,729,995 | Characteristics and clinical manifestations of monkeypox among people with and without HIV in the United States a retrospective cohort. | To compare characteristics and clinical manifestations of monkeypox (MPX) between people with and without HIV in the United States. Retrospective cohort study using TriNetX, a federated research network. Patients 18 years and older with MPX were identified based on the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code B04 and divided into two groups people with HIV (PWH) and people without HIV. Differences in baseline characteristics, clinical manifestations, and all-cause healthcare utilization were examined between groups. Outcomes were reported before and after propensity score matching. Of 322 cases of MPX included, 29% ( n 93) were PWH. Baseline characteristics were similar, but PWH were more likely to identify as Black or African American persons (24% vs. 11%, P 0.0303) or as Hispanic or Latino persons (24% vs. 11%, P 0.0345) and more likely to report lifestyle factors affecting health status. Rash and rectal pain were more common in PWH (25% vs. 11%, P < 0.01, and 25% vs. 10%, P < 0.001, respectively). In addition, PWH had higher rates of anal or rectal abscesses (11% vs. 0%, P < 0.0001), phimosis (11% vs. 0%, P < 0.0001), and pneumonia (11% vs. 0%, P < 0.0001). More PWH required urgent care visits (53% vs. 29%, P < 0.0001) and hospitalizations (11% vs. 4%, P 0.0314), but not emergency department visits (42% vs. 58%, P 0.0085). PWH had higher rates of clinical manifestations and required greater utilization of healthcare resources for any reason compared with those without HIV. |
36,729,993 | HIV Testing Preferences and Characteristics of Those Who Have Never Tested for HIV in the United States. | The initial phase of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative prioritized efforts in 57 geographic areas. The US Centers for Disease Control and Prevention recommends persons aged 13 to 64 years be tested for HIV at least once as part of routine health care however, it is unclear how effectively these testing recommendations have been implemented in EHE priority areas. In 2021 to 2022, we analyzed data from a Web-based, nationally representative survey of adults fielded in 2021. HIV testing preferences were compared by testing history, demographic characteristics, behaviors, and geography. An estimated 72.5% of US adults had never tested for HIV. Never testing was most prevalent among those aged 18 to 29 or those 50 years or older, non-Hispanic White persons, and those living in the Midwest. Among persons living in EHE priority areas and persons reporting at least one behavior that increases risk of HIV transmission, 69.1% and 48.0%, respectively, had never tested for HIV. The top 3 HIV testing preferences among never testers were as follows testing for HIV during a routine health care visit (41.2%), testing at an urgent care or walk-in clinic (9.6%), and self-testing (8.1%). Most adults had not been tested for HIV, confirming that US Centers for Disease Control and Prevention recommendations are not being fully implemented, even in EHE priority areas. Moreover, most adults who never tested preferred testing in clinical settings, highlighting missed opportunities. As the EHE initiative continues to advance, it is critical to leverage preferred HIV testing modalities, such as routine testing in clinical settings or HIV self-testing. |
36,729,982 | ROAR ED-SANE A Retrospective Observational Assessment Review of an Emergency Department Sexual Assault Nurse Examiner Programs Adherence to Centers for Disease Control and Prevention Guidelines for Sexually Transmitted Infections. | Sexual assault survivors are at increased risk for sexually transmitted infections. Sexual Assault Nurse Examiner programs guide sexually transmitted infection treatment, monitoring, and follow-up scheduling according to guidelines by the Centers for Disease Control and Prevention (CDC). Reported low rates of provider adherence to CDC treatment guidelines and patient adherence to follow-up necessitate a review of medication prescribing and follow-up scheduling practices, especially at smaller community hospitals in the United States. A retrospective medical record review was conducted to assess adherence rates to CDC guidelines for prescribing practices, scheduling, and follow-up of sexual assault survivors. We included pediatric and adult patients presenting to the emergency department (ED) and participating in the ED Sexual Assault Nurse Examiner program at a rural, community-based teaching hospital in La Crosse, WI, from January 2018 to December 2021. Descriptive statistics were used to evaluate results. Analysis included 103 patients. Prescribing adherence to CDC guidelines was >80% for all except human immunodeficiency virus (53.4%), trichomoniasis (68.1%), and hepatitis B (69%). Of the 38 patients who had a follow-up scheduled during their ED encounter, 78.9% attended their scheduled follow-up and 94.7% of those appointments were scheduled within the CDC-recommended time frame, leading to an overall adherence of 40%. Adherence rates were high for most prescribing practices, and attendance of scheduled follow-up was higher than expected. Opportunities to improved adherence to CDC guidelines were identified in prescribing for 3 disease states (human immunodeficiency virus, trichomoniasis, and hepatitis B) and in scheduling of follow-up. |
36,729,966 | Epidemiologic evidence on the role of Lactobacillus iners in sexually transmitted infections and bacterial vaginosis a series of systematic reviews and meta-analyses. | While Lactobacillus crispatus-dominated vaginal microbiotas are thought to protect against bacterial vaginosis (BV) and sexually transmitted infections (STIs), the role of Lactobacillus iners-dominated microbiotas is less clear. To better understand the impact of L. iners on common cervicovaginal infections, we conducted systematic reviews of the associations between L. iners compared to L. crispatus and eight outcomes Chlamydia trachomatis (Ct), BV, HPV, cervical dysplasia, HIV, genital herpes, Trichomonas vaginalis, and Neisseria gonorrhoeae. On April 30, 2021, we searched PubMed, Embase, Cochrane Library, and Web of Science for epidemiologic studies of reproductive-age, nonpregnant, cisgender women that used marker gene sequencing to characterize vaginal microbiota composition and presented an effect estimate for the association between L. iners, compared to L. crispatus, and outcomes of interest. For outcomes with >3 eligible results presenting the same form of effect estimate, we conducted random-effects meta-analysis. The review protocol was registered prospectively (PROSPERO CRD42020214775). Six Ct studies were included in meta-analysis, which showed L. iners-dominated microbiotas were associated with 3.4-fold higher odds of Ct compared to L. crispatus-dominated microbiotas (95% CI 2.1-5.4). Three BV studies were included in meta-analysis, which indicated L. iners-dominated microbiotas were associated with 2.1-fold higher prevalence of BV compared to L. crispatus-dominated microbiotas (95% CI 0.9-4.9). Evidence was too sparse to perform meta-analysis for the remaining outcomes. L. iners-dominated vaginal microbiotas may be suboptimal compared to L. crispatus-dominated microbiotas for BV and Ct. These reviews highlight evidence gaps regarding the remaining outcomes and opportunities to improve epidemiologic rigor in vaginal microbiome science. |
36,729,961 | Gestational weight gain in persons living with HIV in the United States results from the PHACS SMARTT study. | We evaluated GWG in pregnant PLHIV enrolled in the Surveillance Monitoring for ART Toxicities study. This was a cohort study. GWG was classified as excessive, adequate, or inadequate weekly GWG in 2nd and 3rd trimesters was calculated using National Academy of Medicine standards. Adjusted modified Poisson and linear regression models were fit with generalized estimating equations to assess the association of antiretroviral treatment (ART) with GWG outcomes stratified by timing of ART initiation at conception (ART-C) and initiating during pregnancy (ART-I). We included 1477 pregnancies (847 ART-C, 630 ART-I) from 1282 PLHIV. The proportion of excessive, adequate, and inadequate GWG was 44%, 24%, and 32% respectively. No associations of ART class with excessive GWG were observed overall. However, among ART-I pregnancies with overweight pre-pregnancy body mass index (BMI), protease inhibitor (PI)-, non-nucleoside reverse transcriptase inhibitor-, and nucleoside reverse transcriptase inhibitor-based ART were associated with significantly lower GWG per week than integrase inhibitor (INSTI)-based ART mean differences -0.14, -0.27, and -0.29 kgwk respectively. Among ART-I pregnancies with obese pre-pregnancy BMI, lower weekly GWG was also observed for PI- vs. INSTI-based ART (mean difference -0.14 kgwk). ART class type was not associated with excessive GWG. However, PLHIV entering pregnancy already overweightobese and initiating INSTI-based ART had higher weekly GWG in 2nd and 3rd trimesters vs. other ART classes. Further studies to understand how increases in weekly GWG for overweightobese PLHIV impinges on long-term maternalchild health are warranted. |
36,729,903 | Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency. | Antibody CAP256-VRC26.25 targets the second hypervariable region (V2) at the apex of the HIV envelope (Env) trimer with extraordinary neutralization potency, although less than optimal breadth. To improve breadth, we linked the light chain of CAP256V2LS, an optimized version of CAP256-VRC26.25 currently under clinical evaluation, to the llama nanobody J3, which has broad CD4-binding site-directed neutralization. The J3-linked bispecific antibody exhibited improved breadth and potency over both J3 and CAP256V2LS, indicative of synergistic neutralization. The cryo-EM structure of the bispecific antibody in complex with a prefusion-closed Env trimer revealed simultaneous binding of J3 and CAP256V2LS. We further optimized the pharmacokinetics of the bispecific antibody by reducing the net positive charge of J3. The optimized bispecific antibody, which we named CAP256.J3LS, had a half-life similar to CAP256V2LS in human FcRn knock-in mice and exhibited suitable auto-reactivity, manufacturability, and biophysical risk. CAP256.J3LS neutralized over 97% of a multiclade 208-strain panel (geometric mean concentration for 80% inhibition (IC |
36,729,857 | HIV in the Russian Federation mortality, prevalence, risk factors, and current understanding of sexual transmission. | Although HIV infection in the Russian Federation was historically concentrated among marginalized populations (people who inject drugs, sex workers, MSM, and the prison population), recent evidence suggests that it has become a more generalized epidemic. The objective of our research was to explore how these trends in HIV prevalence and HIV-related mortality compare across Russia. We calculated HIV-associated mortality for both male and female individuals in each region (oblast) of the Russian Federation using data from the Russian Fertility and Mortality Database (RusFMD). Using current data on HIV prevalence, we computed the correlation between HIV prevalence and HIV-associated mortality. We also used oblast-level data to examine the associations between HIV prevalence and the risk factors most commonly associated with HIV infection. Over the past 20 years, the Russian Federation has experienced a rapid increase in HIV-associated mortality in both male and female individuals. Our findings revealed significant heterogeneity, with higher rates of HIV-associated mortality reported in oblasts in the Siberian and Ural Federal Districts. There is a strong correlation (0.8) between HIV-associated mortality and virus prevalence. These findings confirm that there are regional disparities in access and adherence to antiretroviral therapy (ART), as indicated by the low correlation (-0.4) between virus prevalence and access to ART coverage. The results from our modeling analysis revealed that, in addition to the factors most commonly associated with this disease (e.g. intravenous drug use), knowledge about sexual transmission of HIV in the general population has a broad impact on its prevalence at the oblast level. Interventions that reduce HIV prevalence, for example, opioid substitution therapy and needle-sharing programs for people who inject drugs, as well as the increased availability of educational and preventive programs may halt the spread of HIV across the Russian Federation. Similarly, increased access to treatment could help in reducing HIV-related mortality. |
36,729,784 | Integrative Review of Methods from Youth Risk Behavior Survey Secondary Data Analyses Examining HIV Syndemic Factors Among Adolescent Gay and Bisexual Men. | Adolescent gaybisexual men exhibit the highest prevalence of undiagnosed HIV infections. Ascertaining antecedents of behaviorally acquired HIV infections among adolescent gaybisexual men can be challenging however, these challenges can be overcome through the utilization of secondary data, such as the Youth Risk Behavior Survey. Syndemics theory suggests that HIV infections are not a singular phenomenon instead, many infections occur at the intersection of syndemic factors, such as substance use, violence, and mental health. Our objective is to describe and synthesize research methods of secondary data analyses that examine syndemic factors in relation to HIV risk behavior outcomes among subsamples of adolescent gaybisexual men. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed, Cumulative Index to Nursing and Allied Health Literature, and PsycInfo were systematically searched. Inclusion criteria were (a) peer-reviewed Youth Risk Behavior Survey secondary data analyses conducted in the United States after 1991, (b) subsamples with adolescent gaybisexual men, (c) one or more syndemic factor(s), and (d) one or more HIV risk behavior outcome(s). We used the National Institutes of Health Quality Assessment Tools for quality appraisal. Of 1,036 citations retrieved, nine studies met inclusion criteria. Results included using logistic regression analysis and data from 2015-2017 in six studies and underpinnings with minority stress theory in four studies. Eight studies omitted raceethnicity in subsamples, and six grouped lesbians with adolescent gaybisexual men. Seven studies examined substance use, six examined violence, and five examined mental health. Condom use and number of partners were the most studied HIV risk behavior outcomes in four studies, while intercourse in the last 3 months was an outcome in only one study. Protective factors were not present. Limitations found the need to highlight better inclusion of raceethnicity and sexual orientation. Adding contemporary survey items is also necessary, such as nonbinary sex and gender identity, access to HIV prevention (condoms, HIV testing, and pre-exposure prophylaxis), and experiences with stigma, to elucidate risk behaviors among populations disproportionately affected by HIV infections, including BlacksAfrican Americans and HispanicsLatinos. |
36,729,763 | Estimating the global impact of coronavirus disease 2019 on people living with HIV. | The COVID-19 pandemic and public health response have directly and indirectly affected broader health outcomes, especially for those with existing chronic conditions, including HIV. We examine our current understanding of the global impact of COVID-19 on people with HIV (PWH). The interaction between COVID-19 and HIV is complex, making it challenging to estimate its true impact on PWH. Evidence to date does not suggest that HIV confers a higher risk of acquiring SARS-CoV-2. However, once acquired, HIV increases the risk of severe COVID-19 and mortality, particularly in immunosuppressed viraemic individuals and in the context of traditional COVID-19 risk factors, including disparities in social determinants of health. In addition, COVID-19 vaccines may be less effective in the context of HIV infection with additional doses needed. The consequences of disruption of access to essential prevention and treatment services because of the pandemic are becoming evident and will likely adversely affect outcomes, risking decades of progress. Given the increased mortality risk and reduced vaccine effectiveness seen in PWH, specific prevention and support measures are needed, including prioritization of vaccination and boosters, funding to mitigate the impact of pandemic and enabling integrated healthcare delivery during pandemics will be critical. |
36,729,748 | The role of the genital microbiota in the acquisition and pathogenesis of sexually transmitted infections. | There are an estimated 374 million new sexually transmitted infections (STIs) worldwide every year. Our review article examines the current evidence of how STI acquisition, transmission, and pathogenesis is impacted upon by the genital microbiota, with a focus on epidemiological, biochemical, and immunological features. At least in women, a genital microbiota dominated by lactobacilli has long been considered optimal for reproductive health, while depletion of lactobacilli may lead to a genital microenvironment dominated by anaerobic pathogens, which can manifest clinically as bacterial vaginosis. Recent research efforts have characterized genital microbiota composition in greater resolution, sometimes at species-level, using proteomics, metabolomics, and deep sequencing. This has enhanced our understanding of how specific microbiota members influence acquisition or clinical manifestation of STI pathogen infection. Other advances include a steady, though still slow, increase in the number of studies that sought to determine the genital (penile or urethral) microbiota of males and how it may impact that of their female partners genital microbiota and risk of STI acquisition. Altogether, these data enabled us to explore the concept that genital microbiota may be sexually transmitted and influence pathogenesis and clinical presentation of other STI. With STI infection rates increasing worldwide, it is important now more than ever to find novel STI prevention strategies. Understanding if and how the genital microbiota is a modifiable risk factor for STI transmission, acquisition, and clinical manifestation may prove to be an important strategy in our efforts to curb morbidity in at risk populations. |
36,729,746 | HIV prevention in individuals engaged in sex work. | People who sell sex remain at disproportionate risk of acquiring HIV and should be prioritized for evidence-based HIV prevention programmes delivered at sufficient scale and intensity for effectiveness. Although new biomedical tools are becoming available, many basic lessons learned early in the HIV pandemic remain salient today and need renewed attention. New preexposure prophylaxis formulations, distribution systems, and delivery mechanisms are being successfully trialled and implemented, adding to well established prevention tools such as male and female condoms and lubricants. The importance of social support networks and community ownership of programmes has been consistently reaffirmed. Serious challenges remain in optimizing HIV prevention for sex workers, including providing services at the scale and intensity necessary for population level impact, addressing culturally sensitive issues of gender identity and sexual orientation, and protecting adolescents and young people who may sell sex. Pervasive social stigma, often reinforced by criminalization and police harassment, further constrain sex workers access to available services and prevention tools. Meaningful community engagement and addressing the multiple social determinants of vulnerability at individual, community, and structural levels remain at the core of preventing HIV among people involved in selling sex. |
36,729,711 | Economic evaluation of improving HIV self-testing among MSM in China using a crowdsourced intervention a cost-effectiveness analysis. | Crowdsourcing, which taps into the wisdom of crowds, has been successful in generating strategies to enhance HIV self-testing (HIVST) uptake. We determined the cost-effectiveness of a crowdsourced intervention (one-off or annual) compared with a control scenario (no crowdsourcing) among MSM living in China. Economic evaluation. We used data from our cluster randomized controlled trial of MSM (NCT02796963). We used a micro-costing approach to measure direct health costs ($USD2017) from a health provider perspective. Using outputs from a dynamic transmission model over a 20-year time horizon, we estimated the incremental cost-effectiveness ratios using cost per disability-adjusted life years (DALYs) averted with 3% discounting. An intervention was considered highly cost-effective if it was less than one gross domestic product (GDP, $8823) per DALY averted. Across all cities, the crowdsourced intervention was highly cost-effective compared with the control scenario (incremental cost-effectiveness ratios ranged from $2263 to 6152 per DALY averted for annual crowdsourcing $171 to 204 per DALY averted for one-off crowdsourcing). The one-off intervention was cost-saving in Guangzhou and Qingdao. Sensitivity analyses confirmed the robustness of the findings specifically, changes in discounting, costs of the crowdsourced intervention, costs of HIV testing and cost of antiretroviral therapy did not alter our conclusions. Scaling up a one-off or annual crowdsourced HIV prevention intervention in four cities in China was very likely to be cost-effective. Further research is warranted to evaluate the feasibility of scaling up crowdsourced HIV prevention interventions in other settings and populations. |
36,729,692 | Long-term clinical, immunologic, and virologic outcomes among early-treated children with HIV in Botswana a nonrandomized controlled clinical trial. | Early antiretroviral treatment (ART) improves outcomes in children, but few studies have comprehensively evaluated the impact of ART started from the first week of life. Children diagnosed with HIV within 96 hours of life were enrolled into the Early Infant Treatment Study in Botswana and followed on ART for 96 weeks. Nevirapine, zidovudine, and lamivudine were initiated nevirapine was switched to lopinavirritonavir between weeks 2-5 in accordance with gestational age. Clinical and laboratory evaluations occurred at weeks 1, 2, 4, 8, 12, 24, 36, 48, 60, 72, 84, and 96. Forty children-initiated ART at a median of 2 (IQR 2, 3) days of life 38 (95%) completed follow-up through 96 weeks, and 2 (5%) died between 12 and 24 weeks. ART was well tolerated 9 (24%) children experienced a grade 3 or 4 hematologic event, and 2 (5%) required treatment modification for anemia. The median 96-week CD4 count was 1625 (IQR 1179, 2493) cellsmm3 with only 538 (13%) having absolute counts <1000 cellsmm3. Although 23 (61%) had at least one visit with HIV-1 RNA ≥40 copiesmL at or after 24 weeks, 28 (74%) had HIV-1 RNA <40 copiesmL at the 96-week visit. Median cell-associated HIV-1 DNA at 8496-week PBMCs was 1.9 (IQR 1.0, 2.6) log10 copies106 cells. Pre-ART reservoir size at birth was predictive of the viral reservoir at 8496 weeks. Initiation of ART in the first week of life led to favorable clinical outcomes, preserved CD4 cell counts, and low viral reservoir through 96 weeks of life. |
36,729,689 | Factors associated with sharing equipment among people who inject drugs The role of community attachment in harm reduction and health promotion. | Sharing injecting equipment is a major route of transmission for blood borne viruses such as hepatitis C and HIV. Although needle and syringe programs are widely available throughout metropolitan Australia, rates of sharing equipment have not significantly changed in recent years. This study aimed to identify factors associated with recent equipment sharing among people who inject drugs in Australia. A paper-based survey was distributed via peer-based organisations between June and November 2018 and was completed by 603 participants. Survey questions addressed recent injecting experiences, equipment sharing, community attachment, stigma and wellbeing. Participants who had recently shared injecting equipment were compared with those who had not shared any equipment using multivariable logistic regression. Recent equipment sharing was associated with recent heroin use, experiencing any past-year stigma related to injecting drug use, and higher levels of attachment to a community of people who inject drugs. An interaction effect showed increased community attachment was associated with increased odds of sharing equipment among young participants, but with decreased odds of sharing equipment among older participants. Community networks of people who inject drugs can play important roles in harm reduction initiatives. While being connected with a community of people who inject drugs increased the odds of sharing injecting equipment, this community connection also increases opportunities for social support, sharing information and mitigating the negative effects of stigma. Collaboratively and meaningfully engaging with communities of people who inject drugs has the potential to increase the reach and effectiveness of health promotion services. |
36,729,682 | Evaluation of Statin Prescribing Practices and Predictors of Statin Underutilization in Persons With HIV. | Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared with those without HIV. Despite the increased risk, PWH are less likely to be prescribed statin therapy compared with the general population. The purpose of this study is to describe the statin prescribing practices of an outpatient HIV clinic and identify potential predictors of statin underutilization. This study was a retrospective, single-center chart review of PWH ages 40-79 years receiving care at an HIV clinic. Statin eligibility, statin prescribing practices, and appropriateness of statin therapy were evaluated. Logistical regression analyses were conducted to assess for predictors of underutilization of statin therapy. Of the 606 patients, statin therapy was indicated in 362 patients (60%). Among those with a statin indication, 60.2% were prescribed appropriate statin therapy, 11.6% were prescribed statin therapy but not at the indicated intensity, and 28.2% were not prescribed statin therapy. Tobacco use ( P 0.0023) was identified as a predictor of statin underutilization. The odds of statin prescribing were higher for those with clinical atherosclerotic CVD ( P 0.004) and hypertension ( P 0.017). Statin underutilization was significantly higher in PWH smoking tobacco and PWH without atherosclerotic CVD or low-density lipoprotein-cholesterol 190 mgdL or higher. In addition, this study highlights the need for more robust CVD prevention efforts in PWH. Identifying predictors of statin underutilization may aid in elucidating where gaps in cardiovascular prevention care may exist. |
36,729,676 | The relationships among stress-responsive biomarkers, ART adherence, and viral suppression among adolescent girls and young women living with HIV in South Africa An HPTN 068 Analysis. | Adolescent girls and young women (AGYW) living with HIV who have higher stress levels may be at risk for stress-related biological alterations, which could influence HIV progression and adherence to antiretroviral therapy (ART). We aimed to estimate associations among stress-responsive biomarkers, ART adherence and viral suppression in AGYW living with HIV in South Africa. We also hypothesized that psychosocial stressors (e.g., depression, food insecurity, low socioeconomic status (SES), HSV-2) would be associated with higher biomarker levels. We utilized 20182019 data from the HIV Prevention Trials Network (HPTN) 068 cohort to assess associations between stress-responsive biomarkers and viral suppression (<1000 copiesmL) and ART adherence measured using dried blood spot (DBS) cards. Stress-responsive biomarkers included C-reactive protein (CRP), Herpes simplex virus type 1 (HSV-1), and cytomegalovirus (CMV) infection and reactivation. Associations were estimated using unadjusted log-binomial or ordinal logistic regression models. In 166 AGYW living with HIV, there was no association between stress-responsive biomarkers and viral suppression or ART adherence. However, increased CRP levels were associated with higher HSV-2 infection (odds ratio (OR) 1.98 95% confidence interval (CI) 1.11, 3.52), being a government grant recipient (OR 3.21 95% CI 1.30, 7.92), lower food insecurity (OR 0.34 95% CI 0.13, 0.90) and increased BMI (OR 1.07 95% CI 1.01, 1.14). High prevalence of psychosocial stressors and persistent herpesviruses in AGYW living with HIV has the potential to lead to poorer health outcomes. More research is needed to untangle relationships between economic stability, chronic disease, and chronic stress. |
36,729,663 | Auditory Function in the Pediatric HIVAIDS Cohort Study Adolescent Master Protocol Up Young Adults A Pilot Study. | To collect and compare selected hearing measures in a pilot study of young adults with perinatally acquired HIV (YAPHIV) and those with perinatal HIV exposure who are uninfected young adults with PHEU (YAPHEU). Cross-sectional hearing measures in YAPHIV and YAPHEU enrolled in the Pediatric HIVAIDS Cohort Study Adolescent Master Protocol (AMP) for Participants 18 Years of Age and Older (AMP Up). Pure-tone air conduction audiometry and distortion product otoacoustic emission (DPOAE) data were collected in 1 visit. A low-frequency pure-tone average (PTA) (LFPTA, at 0.25, 0.5, 1, and 2 kHz), a speech-frequency PTA (SFPTA, at 0.5, 1, 2, and 4 kHz), and a high-frequency PTA (HFPTA, at 3, 4, 6, and 8 kHz) were calculated. Hearing loss was defined as worse ear SFPTA of ≥20 dB HL. Separate linear regression models were fit for worse ear LFPTA, SFPTA, and HFPTA to assess associations with PHIV status. DPOAE signal-to-noise ratios (SNRs) were obtained at 3 frequencies in each ear. Forty-seven YAPHIV and 9 YAPHEU completed hearing testing. All adjusted mean PTAs were similar between YAPHIV and YAPHEU. Hearing loss occurred more in YAPHIV (747, 15.2% 95% CI 6.3%-28.9%), compared with YAPHEU (09, 0%). No associations were detected between HIV disease severity measures and worse ear SFPTA. DPOAE SNRs were similar between YAPHIV and YAPHEU. In this pilot study, peripheral hearing (ie, PTAs) and cochlear function (ie, DPOAEs) were similar between YAPHIV and YAPHEU. A larger study is warranted to confirm these findings. |
36,729,626 | Effectiveness of Cefixime for the Treatment of Neisseria gonorrhoeae Infection at 3 Anatomic Sites A Systematic Review and Meta-Analysis. | To treat Neisseria gonorrhoeae infection, the Centers for Disease Control and Prevention recommends a single oral dose of cefixime as an alternative to injectable ceftriaxone. We conducted a systematic review and meta-analysis to describe the effectiveness of cefixime in treating N. gonorrhoeae infection at 3 different anatomic sites.We searched PubMed and Embase database to abstract treatment success rates and cefixime dosagefrequency for studies that reported the anatomical site of infection. We included reports published between January 1, 1980, and December 7, 2021. Twenty studies published between 1989 and 2015 were included in our meta-analysis. We calculated pooled treatment success percentages and 95% confidence intervals (CIs) using random-effects models. Of patients who received a 400-mg single dose of cefixime, 824 of 846 (97% 95% CI, 96%-98%) patients with urogenital infection, 107 of 112 (97% 95% CI, 84%-100%) patients with rectal infection, and 202 of 242 (89% 95% CI, 76%-96%) patients with pharyngeal infection were cured. Of patients who received an 800-mg single dose of cefixime, 295 of 301 (98% 95% CI, 96%-99%) patients with urogenital infection and 21 of 26 (81% 95% CI, 61%-92%) patients with pharyngeal infection were cured. Our meta-analysis found that cefixime is highly effective at treating urogenital infections and less effective at treating pharyngeal infections. We recommend more investigation into the effectiveness of cefixime in treating rectal infections and studying multidose therapy for the cefixime treatment of pharyngeal infection. |
36,729,541 | Decentralized, integrated treatment of RRMDR-TB and HIV using a bedaquiline-based, short regimen is effective and associated with improved HIV disease control. | In decentralized sites, with fewer resources and a high prevalence of advanced HIV, the effectiveness of the new short-course, bedaquiline-based regimen for rifampicin-resistant and multidrug-resistant tuberculosis (RRMDR-TB) is not well-described. Adults with pulmonary RRMDR-TB initiating the short-course regimen in KwaZulu-Natal, South Africa were prospectively enrolled at a decentralized program that integrated person-centered TB care. In addition to standard of care monitoring, study visits occurred at enrollment and months 1, 2, 4, 6 and 9. Favorable RRMDR-TB outcome was defined as cure or treatment completion without loss to follow-up, death or failure by treatment. In patients with HIV, we assessed ART uptake, virologic and immunologic outcomes. Among 57 patients, HIV was present in 73.7% (95% CI 60.3-84.5), with a median CD4 count of 170 cellsmm3 (intraquartile range (IQR) 49-314). A favorable RRMDR-TB outcome was achieved in 78.9% (CI 67.1-87.9). Three deaths occurred, all in the setting of baseline advanced HIV and elevated viral load. Overall, 21.1% (95% CI 12.1-32.9) experienced a severe or life-threatening adverse event, the most common of which was anemia. Among patients with HIV, enrollment resulted in increased ART uptake by 24% (95% CI 12.1-39.4%), a significant improvement from baseline (P0.004) virologic suppression during concomitant treatment was observed in 71.4% (n30, 95% CI 55.4-84.3). Decentralized, person-centered care for RRMDR-TB in patients with HIV using the short-course, bedaquiline-based regimen is effective and safe. In patients with HIV, enrollment led to improved ART utilization and reassuring virologic outcomes. |
36,729,538 | Evaluation of the Revised Versus Original Ryan White Part A HIV Care Coordination Program in a Cluster-Randomized, Stepped-Wedge Trial. | To address challenges with delivery of an evidence-based HIV care coordination program (CCP), the New York City Health Department initiated a CCP redesign. We conducted a site-randomized stepped-wedge trial to evaluate effectiveness of the revised versus the original model. The CCP is delivered in New York City hospitals, community health centers, and community-based organizations to people experiencing or at risk for poor HIV outcomes. The outcome, timely viral suppression (TVS), was defined as achievement of viral load <200 copiesmL within 4 months among enrollees with unsuppressed viral load (≥200 copiesmL). Seventeen original-CCP provider agencies were randomized within matched pairs to early (August 2018) or delayed (May 2019) starts of revised-model implementation. Data from 3 periods were examined to compare revised versus original CCP effects on TVS. The primary analysis of the intervention effect applied fully conditional maximum likelihood estimation together with an exact, conditional P -value and an exact test-based 95% CI. We assigned each trial enrollee the implementation level of their site (based on a three-component measure) and tested for association with TVS, adjusting for period and study arm. Over 3 nine-month periods, 960 individuals were eligible for trial inclusion (intention to treat). The odds ratio of TVS versus no TVS comparing revised with original CCP was 0.88 (95% CI 0.45, 1.7). Thus, the revised program yielded slightly lower TVS, although the effect was statistically nonsignificant. TVS was not significantly associated with revised-CCP implementation level. Program revisions did not increase TVS, irrespective of the implementation level. |
36,729,506 | Automated In Vivo High-Resolution Imaging to Detect Human Papillomavirus-Associated Anal Precancer in Persons Living With HIV. | In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. The HRME, a fiber-optic fluorescence microscope, was used to capture real-time images of anal squamous epithelial nuclei. Nuclear staining is achieved using 0.01% wtvol proflavine, a topical contrast agent. HRME images were analyzed by a multitask deep learning network (MTN) that computed the probability of AIN 2 for each HRME image. The study accrued data from 77 people living with HIV. The MTN achieved an area under the receiver operating curve of 0.84 for detection of AIN 2. At the AIN 2 probability cutoff of 0.212, the MTN achieved comparable performance to expert HRA impression with a sensitivity of 0.92 ( P 0.68) and specificity of 0.60 ( P 0.48) when using histopathology as the gold standard. When used in combination with HRA, this system could facilitate more selective biopsies and promote same-day AIN2 treatment options by enabling real-time diagnosis. |
36,729,467 | A Mixed-methods Evaluation of an AddictionCardiology Pilot Clinic With Contingency Management for Patients With Stimulant-associated Cardiomyopathy. | Contingency management (CM) is one of the most effective treatments for stimulant use disorder but has not been leveraged for people with stimulant-associated cardiomyopathy (SA-CMP), a chronic health condition with significant morbidity and mortality. We aimed to determine the feasibility and acceptability of a multidisciplinary addictioncardiology clinic with CM for patients with SA-CMP and to explore barriers and facilitators to engagement and recovery. We recruited patients with a hospitalization in the past 6 months, heart failure with reduced ejection fraction (<40%) and stimulant use disorder to participate in Heart Plus, a 12-week addictioncardiology clinic with CM in an urban, safety-net, hospital-based cardiology clinic, which took place March 2021 through June 2021. Contingency management entailed gift card rewards for attendance and negative point-of-care urine drug screens. Our mixed-methods study used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. We obtained data from the medical record, staff surveys, and qualitative interviews with participants. Thirty-eight patients were referred, 17 scheduled an appointment, and 12 attended the intake appointment and enrolled in the study. Mean treatment duration was 8 of 12 weeks. Of the 9 participants who attended more than one visit, the median attendance was 82% of available visits for in-person visits and 83% for telephone visits, and all patients reported decreased stimulant use. Delivering CM through a multidisciplinary addictioncardiology clinic for patients with SA-CMP was feasible and engaged patients in care. Further research is needed to assess whether this program is associated with improved heart failure outcomes. |
36,729,360 | Antiretroviral Options and Treatment Decisions During Pregnancy. | The majority of pediatric human immunodeficiency virus (HIV) infections are the result of vertical transmissions that occur during pregnancy, childbirth, and breastfeeding. The treatment of all pregnant persons living with HIV remains a global health initiative. Early and consistent use of antiretroviral therapy throughout pregnancy and childbirth drastically reduces the risk of perinatal transmission of HIV, resulting in fewer children living with the disease worldwide. Given that the maternal HIV viral load is the strongest predictor of perinatal transmission, suppressive antiretroviral treatment during pregnancy is the principal means to eliminate transmission of HIV from mother to child. With the use of combined antiretroviral therapy, typically with dual-nucleoside reverse transcriptase inhibitors plus an integrase strand transfer inhibitor or a ritonavir-boosted protease inhibitor, HIV-infected mothers can now achieve virologic suppression to undetectable levels and yield a perinatal transmission rate of less than 2%. Important considerations of HIV treatment in pregnancy include the safety and efficacy of antiretroviral drugs, altered pregnancy-related pharmacokinetics, potential for birth defects or adverse neonatal outcomes, and individualized delivery planning based on maternal viral load. This practical review article summarizes the options, considerations, and recommendations for antiretroviral treatment in pregnancy to reduce perinatal HIV transmission and optimize health outcomes for mothers and infants worldwide. |
36,729,300 | Effect of coinfections on neurocognitive functioning among people with clade C HIV infection in Zambia. | Despite the fact that many coinfections in people with HIV (PWH) are treatable or suppressible, they may still impact neurocognitive (NC) functioning. Here, we aim to evaluate the presence of latenttreated coinfections and their association with NC functioning in a cohort of PWH in Zambia. We carried out a cross-sectional, nested study involving 151 PWH with viral suppression, and a normative sample of 324 adults without HIV. Plasma samples from PWH who underwent a comprehensive NC assessment were evaluated for the presence of treatedlatent coinfections that are common in Zambia. Information about treated pulmonary tuberculosis (TB) was obtained from participants clinical charts. Overall, PWH differed significantly from the HIV seronegatives on all neuropsychological domains except for fine motor control. ANOVA comparisons of all 3 HIV groups demographically corrected mean NC T-scores showed that the HIV TB group had the poorest NC functioning in the following domains executive functioning (F 4.23, p 0.02), working memory (F 5.05, p 0.002), verbal fluency (F 4.24, p 0.006), learning (F 11.26, p < 0.001), delayed recall (F 4.56, p 0.01), and speed of information processing (F 5.16, p 0.005) this group also was substantially worse on the total battery (global mean T-scores F 8.02, p < 0.001). In conclusion, treated TB coinfection in PWH was associated with worse NC performance compared to both those with antibodies against other coinfections and without. PWH with antibodies for other coinfections (HIV CI ) showed somewhat better NC performance compared to those without (HIV CI -), which was not expected, although comparisons with the HIV CI group are limited by its lack of specificity regarding type of coinfection being represented. |
36,729,293 | Precarious Housing Associated with Unsuppressed Viral load, sub-optimal Access to HIV Treatment and Unmet Health care Needs, Among Women Living with HIV in Metro Vancouver, Canada. | We investigated associations between (1) housing status (four categories measuring housing stability) and outcomes along the HIV care continuum (not currently on antiretroviral therapy ART sub-optimal ART adherence < 95% in the last 3-4 weeks unsuppressed viral load > 200 copiesml, median CD4 < 200 in the last six months), and (2) housing status and unmet primary, dental and mental health care needs in the last six months among WLWH. Housing status was defined according to the Canadian Definition of Homelessness and had four categories unsheltered (i.e., living in ≥ 1 unsheltered location e.g., street, abandoned buildings), unstable (i.e., living in ≥ 1 unstable location e.g., shelter, couch surfing), supportive housing (i.e., only living in supportive housing), and stable housing (i.e., only living in ones own housing reference). At baseline, in the last six months, 47.3% of participants reported unstable housing, followed by 24.4% unsheltered housing, 16.4% stable housing, and 11.9% supportive housing. Overall, 19.1% of the full sample (N 336, 2010-2019) reported not currently on ART among participants on ART, 28.0% reported sub-optimal ART adherence. Overall, 32.1% had recent unsuppressed viral load. Among a subsample (n 318, 2014-2019), 15.7% reported unmet primary care needs, 26.1% unmet dental care needs, and 16.4% unmet mental health care needs. In adjusted models, being unsheltered (vs. stable housing) was associated with not currently on ART, unsuppressed viral load, and unmet primary and dental care needs. Housing and health services need to be developed with and for WLWH to address structural inequities and fulfill basic rights to housing and health. |
36,729,092 | The PrEP Care Continuum Among Mexican Men Who Have Sex with Men and Transwomen a Qualitative Study. | This article describes perceptions and experiences related to the pre-exposure prophylaxis (PrEP) care continuum of Mexican men who have sex with men (MSM) and transwomen (TW). Between June and July 2020, we applied 24 online semi-structured interviews regarding PrEP use with 10 PrEP users, six ex-users, and eight potential users (at risk, not enrolled). Awareness TW did not always receive the information they needed from trusted people. Acceptability Potential users were reluctant to use PrEP due to fear of side effects, and only a few participants worried about stigma. Uptake Potential users missed their enrollment visit and did not know how to reschedule. Adherence Barriers included routine changes interfering with PrEP-taking habits (arriving home later, traveling, etc.) while feeling protected was reported as a facilitator. Retention Ex-users quit PrEP services, mostly without reducing their HIV risk, because of difficulties keeping appointments and fearing long-term effects. Inclusive awareness activities, tackling misbeliefs regarding side effects, and more flexible services may improve PrEP usage and enhance its impact. |
36,728,996 | Selenium and Zinc supplementation in HIV-infected patients. | null |
36,728,933 | Hypertension and one-year risk of all-cause mortality among women with treated HIV in the United States. | Hypertension is a critical cause of cardiovascular disease, and women with HIV have a higher prevalence of hypertension than women without HIV. The relationship between hypertension and mortality has not been well characterized in women with treated HIV. Here, we estimate the effect of hypertension on 1-year risk of all-cause mortality among women with HIV on antiretroviral therapy (ART) in the United States. An analysis of multicenter, observational cohort data from the Womens Interagency HIV Study (WIHS) collected between 1995 and 2019. We included women with HIV who reported ever using ART. We used parametric g-computation to estimate the effect of hypertension (SBP ≥140 mmHg, DBP ≥90 mmHg, or use of hypertensive medication) on all-cause mortality within 1 year of a WIHS visit. Among 2929 unique women, we included 57 034 visits with a median age of 45 (interquartile range 39, 52) years. Women had hypertension at 34.5% of visits, and 641 deaths occurred within 1 year of a study visit. Comparing women at visits with hypertension to women at visits without hypertension, the standardized 1-year risk ratio for mortality was 1.16 95% confidence interval (95% CI) 1.01-1.33. The risk ratios were higher in Hispanic (risk ratio 1.23, 95% CI 0.86-1.77) and non-Hispanic black women (risk ratio 1.19, 95% CI 1.04-1.37) and lower in non-Hispanic white women (risk ratio 0.93, 95% CI 0.58-1.48). Among women with treated HIV, those with hypertension, compared with those without, had an increased 1-year risk of all-cause mortality. |
36,728,918 | Copd And The Risk For Myocardial Infarction By Type In People With Hiv. | The relationship between chronic obstructive pulmonary disease (COPD) and cardiovascular disease in people with HIV (PWH) is incompletely understood. We determined whether COPD is associated with risk of myocardial infarction (MI) among PWH, and if this differs for type 1 (T1MI) and type 2 (T2MI). We utilized data from 5 sites in the CFAR Network of Integrated Clinical Systems (CNICS) cohort, a multi-site observational study. Our primary outcome was an adjudicated MI, classified as T1MI or T2MI. We defined COPD based on a validated algorithm requiring COPD diagnosis codes and ≥90-day continuous supply of inhalers. We conducted time-to-event analyses to first MI and used multivariable Cox proportional hazards models to measure associations between COPD and MI. Among 12,046 PWH, 945 had COPD. Overall, 309 PWH had an MI 58% had T1MI (N 178) and 42% T2MI (N 131). In adjusted models, COPD was associated with a significantly increased risk of all MI adjusted hazard ratio (aHR) 2.68 (95%CI 1.99-3.60) even after including self-reported smoking aHR 2.40 (95%CI 1.76-3.26). COPD was also associated with significantly increased risk of T1MI and T2MI individually, and with sepsis and non-sepsis causes of T2MI. Associations were generally minimally changed adjusting for substance use. COPD is associated with a substantially increased risk for MI, including both T1MI and T2MI, among PWH. Given the association with both T1MI and T2MI, diverse mechanistic pathways are involved. Future strategies to decrease risk of T1MI and T2MI in PWH who have COPD are needed. |
36,728,912 | The role of social support on cognitive function among midlife and older adult men who have sex with men. | This study examines the association between social support and cognitive function among midlife and older men who have sex with men (MSM) living with or without HIV. We analyzed longitudinal data from participants enrolled from October 2016 to March 2019 in the Patterns of Healthy Aging Study, a substudy of the Multicenter AIDS Cohort Study. We conducted a cross-sectional analysis to estimate the association between social support and three measures of cognitive function (Trail Making Test TMT Part A, TMT Part B to A ratio, and Symbol Digit Modalities Tasks SDMT). We also used linear mixed-effects models to estimate the association between baseline social support and cognitive function across four subsequent time points. We evaluated a multiplicative interaction term between baseline social support and time, in order to determine whether cognitive trajectories over time vary by baseline social support. Social support was associated with lower TMT Part A scores at baseline and over the subsequent 2 years, indicating better psychomotor ability. Social support was associated with higher SDMT scores at baseline and across 2 years, indicating better information processing. We observed no association between social support and TMT B to A ratio at baseline or across 2 years, indicating no effect on set-shifting ability. Longitudinal cognition outcome trajectories did not vary by level of baseline social support. Social support and cognitive function were associated in this sample over a short time period. Further research should explore causal relationships over the lifespan. |
36,728,909 | Creatinine and cystatin C-based eGFR estimate of kidney function in black people with HIV on antiretroviral therapy. | To reduce health inequalities, the creatinine-based CKD-EPI 2021 formula for estimated glomerular filtration rate (eGFR) is replacing the 2009 formula which required adjustment specifically for Black individuals. We compared the 2021 and 2009 creatinine-based formulae with cystatin C-based eGFR in Black people on antiretroviral therapy (ART) with HIV RNA <200 cmL. Cross sectional analysis of paired serum creatinine and cystatin C measurements. Bias, imprecision, accuracy, and performance for identifying individuals with eGFR cystatin C <60 (units mLmin1.73m2) were determined. The effects of ART with no, mild-moderate, or marked effect on tubular creatinine secretion on the performance of the 2021 formula was assessed. We included 362 individuals (mean age 51 years, 56% female, mean eGFR-cystatin C 88.3). Overall, the 2021 (vs. the 2009 race-adjusted) formula was less biased and had improved imprecision and accuracy compared with eGFR-cystatin C but underestimated eGFR-cystatin C in those with eGFR ≥90 and overestimated eGFR-cystatin C in those with eGFR <60. The 2021 (vs. the 2009) formula had high specificity (95% vs. 97%) and negative predictive value (97% vs. 96%), but low sensitivity (56% vs. 52%) and positive predictive value (44% vs. 54%) for identifying individuals with eGFR-cystatin C <60 (p > 0.25). Performance at the eGFR <60 cut-off was minimally affected by ART exposure group. The CKD-EPI 2021 creatinine-based formula was better aligned with eGFR-cystatin C than the 2009 formula. eGFR-cystatin C may provide clinically useful information in Black people with eGFR <60 irrespective of ART regimen. |
36,728,856 | Beyond Antiretroviral Treatment Patterns and Factors Associated with Composite Medication Adherence Before and During the COVID-19 Pandemic in Patients with HIV with Multiple Chronic Conditions. | Polypharmacy for multiple chronic conditions (MCCs) poses an increasing challenge in people with HIV (PWH). This research explores medication adherence in PWH with MCCs before and during COVID-19. Kaiser Permanente Mid-Atlantic States. Medical and pharmacy records of a continuously-enrolled cohort (92018-92021) of adult PWH were used. To estimate medication adherence, monthly proportion of days covered (PDC) was measured individually for antiretrovirals (ARVs), diabetes medications (DMs), renin-angiotensin antagonists (RASMs), and statins (SMs) and combined into composite measures (CMs) with and without ARVs. Descriptive statistics, time-series models, and multivariable population-averaged panel general estimating equations were used to profile trends, effects, and factors associated with adherence. The cohort (n543) was predominantly 51-64 years old (59.3%), Black (73.1%), male (69.2%), and commercially insured (65.4%). Two-thirds (63.7%) of patients were taking medications in two medication groups (i.e., ARVs and either DMs, RASMs, or SMs), 28.9% were taking medications in three medication groups, and 7.4% were taking medications in all four medication groups. Overall, PDC for CMs without ARVs was 77.2% and 70.2% with ARVs. After 32020, negative monthly trends in PDC were observed for CMs without ARVs (β-0.1%, p0.003) and with ARVs (β-0.3%, p0.001). For CMs with ARVs, Black race (aOR0.5 p<0.001 ref White) and taking medications for three medication groups (aOR0.8 p<0.02 ref 2) were associated with lower adherence. Decreasing medication adherence trends were observed during the COVID-19 pandemic with variations among population subgroups. Opportunity exists to improve medication adherence for non-White populations and those taking medications for MCCs beyond ARVs. |
36,728,850 | The nationwide trends in hospital admissions, deaths, and costs related to hepatitis C stratified by psychiatric disorders and substance use an analysis of US hospitals between 2016 and 2019. | Hepatitis C virus (HCV) is a prominent liver disease that often presents with mental illness. We stratify the HCV population and review its healthcare burden on the US hospital system. The US National Inpatient Sample was used to select admissions related to HCV between 2016 and 2019. Weights were assigned to discharges, and trend analyses were performed. Strata were formed across demographics, comorbidities, psychiatric and substance use conditions, and other variables. Outcomes of interest included hospitalization incidences, mortality rates, total costs, and mean per-hospitalization costs. From 2016 to 2019, there were improvements in mortality and hospitalization incidence for HCV, as well as a decline in aggregate costs across the majority of strata. Exceptions that showed cost growth included admissions with multiple psychiatric, stimulant use, or poly-substance use disorders, and a history of homelessness. Admissions with no psychiatric comorbidities, admissions with no substance use comorbidities, and admissions with housing and without HIV comorbidity showed decreasing total costs. Along with per-capita mean costs, admissions with comorbid opioid use, bipolar, or anxiety disorder showed significant increases. No significant trends in per-capita costs were found in admissions without mental illness diagnoses. Most strata demonstrated decreases in hospitalization incidences and total costs surrounding HCV however, HCV cases with mental illness diagnoses saw expenditure growth. Cost-saving mechanisms for these subgroups are warranted. |
36,728,672 | Factors associated with reduced function and quality of life among adult plwh with depression and substance use in the asia-pacific region. | Depression and substance use (SU) disorders are prevalent among people living with HIV (PLWH) and impact health outcomes despite successful antiretroviral therapy (ART). We explored quality of life, functional ability and associated factors among PLWH screened positive for depression andor SU. This cross-sectional study recruited adult PLWH during routine follow-up at five HIV clinical sites in the Asia-Pacific region. Participants were screened for depression using PHQ-9 and SU using ASSIST. Quality of life (QoL) was assessed with WHOQOL-HIV BREF and functional ability with WHODAS 2.0. Factors associated with mean QoL and disability scores were analysed using linear regression. Of 864 PLWH enrolled, 753 screened positive for depression or SU. The median (interquartile range, IQR) age was 38 (31-47) years and 97% were on ART. Overall mean WHOQOL-HIV BREF and WHODAS scores indicated greater impairment with increasing depressive symptom severity and SU risk. In multivariate analysis, PLWH reporting previous traumastress (difference 2.7, 95% CI 1.5 to 3.9, p < 0.001) and past mental health diagnosis (difference 5.0, 95% CI 2.9 to 7.1, p < 0.001) were associated with greater disability and poorer QoL scores across multiple domains (p<0.01 for all). Higher CD4 T-cell counts was also associated with better QoL scores and functional ability. PLWH with depressionSU experienced poorer QoL and function despite routine engagement in HIV care. Efforts to integrate mental health services and interventions addressing disability into HIV management should be prioritised in the region. |
36,728,652 | Effect of HIV stigma on depressive symptoms, treatment adherence, and viral suppression among youth with HIV. | We estimated the effects of HIV stigma on mental health and treatment outcomes for youth with HIV (YWHIV). Secondary analysis of data for YWHIV ages 15-24 years in Western Kenya. Participants completed a longitudinal survey (baseline, month 6 and 12) assessing socio-demographics, antiretroviral therapy (ART) adherence, depressive symptoms (PHQ-9), and HIV stigma (10-item Wright scale). First viral load (VL) after enrollment was abstracted from records. We estimated risk of depressive symptoms (score>4), non-adherence (missing ≥2 days of ART in a month), and detectable VL (≥50 copiesml) for each standard deviation (SD) increase in HIV stigma score, adjusted for age and gender (and regimen in VL model). The generalizing estimating equation models included measures for the 3 visits. Median age for the 1,011 YWHIV was 18 years. At baseline, frequency of non-adherence, depressive symptoms and detectable VL was 21%, 21% and 46%, respectively. Mean stigma score was 25 (SD 7.0). Each SD stigma score increment was associated with higher risk of depressive symptoms (adjusted relative risk aRR 1.31 95% confidence interval CI 1.20-1.44), non-adherence (aRR 1.16 CI 1.05-1.27) and detectable VL (aRR 1.20 CI 1.08-1.32). Experienced and anticipated stigma were associated with detectable VL (aRR 1.16 CI 1.10-1.22 and aRR 1.23 CI 1.12-1.35 respectively). Internalized and perceived community stigma were associated with depressive symptoms (aRR 1.31 CI 1.21-1.40 and aRR 1.24 CI 1.13-1.36 respectively). Stigma was associated with depressive symptoms, non-adherence and detectable VL. Interventions to decrease stigma may improve virologic and mental health outcomes in YWHIV. |
36,728,618 | EPIDEMIOLOGY OF TUBERCULOSIS AMONG PEOPLE LIVING WITH HIV IN THE AFRICAN COHORT STUDY FROM 2013-2021. | The prevalence and incidence of tuberculosis (TB) is high among persons living with HIV (PLWH), but is often under-diagnosed in HIV programmatic settings. Presidents Emergency Plan for AIDS Relief (PEPFAR)-supported research sites in Uganda, Kenya, Tanzania, and Nigeria. All patients underwent molecular testing at entry into a longitudinal cohort of PLWH, and annually thereafter. We assessed prevalence and incidence of TB and identified clinical and demographic factors associated with prevalent and incident TB using logistic regression and Cox proportional hazard models. From January 2013 to 1 December 2021, 3,171 PLWH were enrolled with a TB prevalence of 3% (n93). Of the prevalent TB cases, 66% (n61) were bacteriologically confirmed. The adjusted odds of prevalent TB were significantly higher among those with higher educational attainment, PLWH for 1-5 years since their HIV diagnosis, those who were underweight, and those with CD4 counts <200 cellsmm3. The overall TB incidence rate was 600 per 100,000 person-years (95% CI 481-748). We found that shorter time since HIV diagnosis, being underweight, taking antiretroviral therapy <6 months, and having a CD4 count <200 cellsmm3, was significantly associated with incident TB. PLWH on dolutegravirlamivudinetenofovir had a 78% lower risk of incident TB compared to those on tenofovirlamivudineefavirenz (Hazard Ratio 0.22 95% CI 0.08-0.63). Prevalence and incidence of TB was notably high in this cohort sourced from PEPFAR clinics. Aggressive efforts to enhance HIV diagnosis and optimize treatment in programmatic settings are warranted to reduce risk of HIV-TB co-occurrence in this cohort. |
36,728,423 | Participation of HIV-1 infected treatment-naïve females in clinical trials and sex differences in efficacy and safety outcomes. | To examine female participation and the observed efficacy and safety by sex from phase 3 HIV-1 trials submitted to the U.S. Food and Drug Administration (FDA) to support approval or a major labeling change. Our analyses were based on phase 3 trials in HIV-1 infected treatment-naïve adults submitted to FDA since 2010. We evaluated enrollment of treatment-naïve females in 18 clinical trials for HIV-1. Participation to prevalence ratio (PPR) was calculated as the percentage of females among trial participants divided by the percentage of females in the disease population. PPR between 0.8 and 1.2 reflects similar representation of females in the trial and the disease population. Sex differences in efficacy (virologic response rates) and selected safety events were evaluated. U.S. females, particularly U.S. black females were not adequately represented in clinical trials. The PPR for U.S. females overall was 0.59 and for U.S. Black females was 0.63. Statistically significant sex differences favoring males were observed for efficacy outcomes in both the global population and U.S. participants. Statistically significant sex differences were observed for some safety outcomes. U.S. females are underrepresented in phase 3 HIV-1 clinical trials. Underrepresentation was not likely due to enrollment criteria. Statistically significant sex differences were noted for efficacy and selected safety outcomes however, some differences were not clinically relevant. The ability to detect sex differences was hindered by low numbers of female participants overall and within subgroups. Additional research into innovative approaches to recruit and retain females in clinical trials should continue. |
36,728,420 | Siglec-9 Restrains Antibody-Dependent Natural Killer Cell Cytotoxicity against SARS-CoV-2. | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters the immunological profiles of natural killer (NK) cells. However, whether NK antiviral functions are impaired during severe coronavirus disease 2019 (COVID-19) and what host factors modulate these functions remain unclear. We found that NK cells from hospitalized COVID-19 patients degranulate less against SARS-CoV-2 antigen-expressing cells (in direct cytolytic and antibody-dependent cell cytotoxicity ADCC assays) than NK cells from mild COVID-19 patients or negative controls. The lower NK degranulation was associated with higher plasma levels of SARS-CoV-2 nucleocapsid antigen. Phenotypic and functional analyses showed that NK cells expressing the glyco-immune checkpoint Siglec-9 elicited higher ADCC than Siglec-9 |
36,728,418 | Fracture prevalence and its association with bone density among children living with HIV in Zimbabwe. | HIV infection impairs bone density in children living with HIV (CLWH). We aimed to determine the prevalence of self-reported fracture (past or current), associated risk factors and disability, by HIV status in Zimbabwean children. Cross-sectional study. We recruited CLWH aged 8-16 years taking antiretroviral therapy (ART) for ≥2 years from HIV clinics, and HIV-uninfected children from schools in Harare. Interviewer-administered questionnaires collected data on fracture site and management, sociodemographics, dietary calcium and vitamin D, physical activity and HIV history. Dual-energy X-ray absorptiometry (DXA) measured size-adjusted bone density. We recruited 303 CLWH (meanSD age 12.52.5 years 50% female) and 306 children without HIV (12.52.5 years 51% female). Median age at HIV diagnosis in CLWH was 3.0 years IQR 1.2, 5.9, and median ART duration 8.1 years IQR 6.2, 9.5. 53.8% CLWH had self-reported disability andor functional impairment, versus 29.4% children without HIV. Fracture prevalence was 5.9% with no difference by HIV status 21306(6.9%) vs. 14303 (4.6%), P 0.24. Male sex was associated with fractures. Low LS-BMAD (Z-score<-2) was associated with prevalent fractures in CLWH (RR 1.14 95%CI -0.02, 2.29), but not in children without HIV (RR -0.04 -2.00, 1.91), p- interaction 0.27. All sought medical attention for their fracture(s), but CLWH were less often admitted to hospital 214(14.3%) vs . 721 (33.3%). Prevalent fractures may be associated with low lumbar spine bone density in CLWH. Fracture surveillance and strategies to reduce future fracture risk are warranted as CLWH enter adulthood. |
36,728,397 | The Impact of COVID-19 Response on the HIV Epidemic in Men Who Have Sex with Men in San Francisco County The Importance of Rapid Return to Normalcy. | In response to the COVID-19 pandemic, San Francisco County (SFC) had to shift many non-emergency healthcare resources to COVID-19, reducing HIV control resources. We sought to quantify COVID-19 effects on HIV burden among men who have sex with men (MSM) as SFC returns to pre-COVID service levels and progresses towards the Ending the HIV Epidemic (EHE) goals. Microsimulation model of MSM in SFC tracking HIV progression and treatment. Scenario analysis where services affected by COVID-19 (testing, care engagement, pre-exposure prophylaxis PrEP uptake and retention) return to pre-COVID levels by the end of 2022 or 2025, compared against a counterfactual where COVID-19 changes never occurred. We also examined scenarios where resources are prioritized to reach new patients or retain of existing patients from 2023-2025 before all services return to pre-COVID levels. The annual number of MSM prescribed PrEP, newly acquired HIV, newly diagnosed, and achieving viral load suppression (VLS) rebound quickly after HIV care returns to pre-COVID levels. However, COVID-19 service disruptions result in measurable reductions in cumulative PrEP use, VLS person-years, incidence, and an increase in deaths over the 2020-2035 period. The burden is statistically significantly larger if these effects end in 2025 instead of 2022. Prioritizing HIV careprevention initiation over retention results in more person-years of PrEP but less VLS person-years and more deaths, influencing EHE PrEP outcomes. Earlier HIV care return to pre-COVID levels results in lower cumulative HIV burdens. Resource prioritization decisions may differentially affect different EHE goals. |
36,728,316 | Testing and Case Rates of Gonorrhea, Chlamydia, Syphilis, and HIV among People with Substance Use Disorders in the Veterans Health Administration. | Little is known about national patterns of sexually transmitted infection (STI) testing and infections among people with substance use disorders (SUDs). This study used a national retrospective analysis of people with SUDs receiving healthcare in the Veterans Health Administration in 2019 (N 485,869). We describe testing rates, test positivity, and case rates for gonorrhea, chlamydia, syphilis, and HIV among individuals with alcohol, opioid, cocaine, and noncocaine stimulant use disorders in a national cohort of Veterans Health Administration patients. Test and case rates for all STIs were highest among people with noncocaine stimulant use. People with alcohol use disorder had the lowest testing rates but intermediate incidence for all STIs. People with multiple SUDs had higher incidence of all STIs than those with single SUDs. Mental health diagnoses and houselessness were common. The HIV test positivity was 0.14% to 0.36% across SUD groups. Sexually transmitted infection testing rates between SUD groups were discordant with their respective case rates. High STI rates in people with SUDs suggest a need for more comprehensive testing, particularly for those with noncocaine stimulant use and those with comorbid houselessness or mental health diagnoses. |
36,728,262 | Assortative sexual mixing by age, region of birth and time of arrival in male-female partnerships in Melbourne, Australia. | Patterns of sexual mixing may be influenced by demographic factors where individuals show a preference for partners with particular traits and may have different levels of risk for HIV and STI transmission. We aimed to explore age differences and mixing by region of birth among male-female partnerships. Male-female partnerships who presented to Melbourne Sexual Health Centre (MSHC) in Australia between 2015 and 2019 were investigated. Age and country of birth of sexual partners were collected. We calculated the age differences between partners and created tables demonstrating partnership mixing by age groups and by international region of birth. A total of 2112 male-female partnerships (i.e., 4224 individuals) were included. The median age was 27 years (IQR 23-31). Between males and females in partnerships, the median age difference was one year, in which the male partner was older than the female partner. Nearly half of all individuals (49.1% 20724224) were in a partnership with another individual in the same five-year interval age group as their own, and the majority of individuals (58.5% 23343988) were in a partnership with another individual from the same region of birth when compared to other regions. There is a strong assortative sexual mixing pattern by age and region of birth among male-female partnerships in Melbourne, Australia. These results may have applications in further research to understand STI transmission among clients attending sexual health centres, particularly those born overseas. |
36,728,250 | The effects of participation in an intensive HIV prevention trial on long term socio-demographic outcomes among young women in rural South Africa. | Research trial participation may influence health outcomes regardless of the intervention assigned but is often not assessed. We investigated how participation in an HIV prevention trial (the HIV Prevention Trials Network (HPTN) 068 study) affected health outcomes four years after the study in adolescent girls and young women (AGYW) in South Africa beyond effects of the tested intervention. We developed an analytical cohort that included the HPTN 068 trial participants from the Agincourt Health and Demographic Surveillance System (AHDSS) and resembled HPTN 068 trial enrollees (aged 13 to 20 years and in grades 8-11 in 2011) using inverse probability of treatment weights. We estimated risk differences (RD) for the association between trial participation and education and early parity (age <20 years) in 2019, after accounting for differences at baseline between the trial participants and non-participants. There were 3,442 young women enrolled in grades 8-11 in 2011 1,669 were in the HPTN 068 trial. Trial participants were more likely to have completed secondary school by 2019 (adjusted RD (aRD) 5.0%, 95% Confidence Interval (CI) 2.2%, 7.9% 82.3% in trial participants vs. 77.2% in non-participants). Trial participants had similar risk of parity before age 20 compared to non-trial participants (aRD 2.3%, 95% CI -0.8%, 5.5%). Trial participation did not appear to influence early parity but did increase educational attainment. Our results are compatible with an explanation of Hawthorne effects from trial participation on schooling behaviors that were small but observable even four years after the end of the trial. |
36,728,249 | Assessing Renal Impairment in Treatment-Naïve Adolescents Living with HIV Commencing Antiretroviral Therapy In Zimbabwe. | People living with HIV (PLWHIV) are increasingly experiencing non-communicable complications, including renal impairment, which are associated with worse clinical outcomes. Limited information exists surrounding renal impairment in paediatric PLWHIV, of which the majority live in sub-Saharan Africa, and further information is required to guide clinical practice. This study describes the prevalence of new or worsening renal impairment in adolescents commencing antiretroviral therapy (ART) in Zimbabwe and associated risk factors. Retrospective cohort study. Data were collected between January 2010 to January 2019 from the medical records of adolescents aged 12-17 years initiating ART at an outpatient HIV clinic in Zimbabwe. Renal function (eGFR) was calculated using the Full Age Spectrum formula. Proteinuria was defined as a single urine dipstick score of ≥1. Potential predictors of renal impairment at follow-up were assessed by logistical regression. 266 adolescents were included in analysis. Baseline renal impairment (eGFR <90 mlmin1.73m2) and proteinuria were present in 13% and 7% of the cohort, respectively. After a median of 4.1 years (IQR 1.9, 6.9) following ART commencement, mean eGFR increased by 10 mlmin1.73m2 (p < 0.01), and the prevalence of renal impairment decreased to 8% (p < 0.01). Baseline renal impairment predicted renal impairment at follow-up (OR 8.98 95%CI 2.81, 28.68 p < 0.01). Proteinuria trended towards association with renal impairment at follow-up (OR 4.39 95%CI 0.95, 20.31 p 0.06). Renal impairment is common in adolescent ART-naïve PLWHIV, and baseline renal impairment is associated with longstanding renal impairment, while baseline proteinuria trended towards an association with longstanding renal impairment. |
36,728,240 | Meningococcus B Vaccination Effectiveness against Neisseria gonorrhoeae Infection in People Living with HIV a Case-control Study. | We assessed the vaccination effectiveness (VE) of multicomponent meningococcal serogroup B (4CMenB) vaccine against gonorrhoea among people living with HIV (PLWH) with a previous diagnosis of sexually transmitted infection (STI). Unmatched case-control study on men who have sex with men (MSM) living with HIV, in care at San Raffaele Scientific Institute, Milan, Italy, with gonorrhoea, syphilis, chlamydia or anal HPV between July 2016 (beginning of 4CMenB vaccination) and February 2021 (date of freezing). For the analysis, cases were people with ≥1 gonorrhoea infection since July 2016 and controls were people with ≥1 syphilis, chlamydia, or anal HPV infection since July 2016. Logistic regression was used to provide the estimate of 4CMenB VE against gonorrhoea. Included PLWH were 1051 (103 cases, 948 controls) 3491051 (33%) received two doses of 4CMenB vaccination. The median follow-up was 3.8 years (2.1-4.3). The unadjusted estimate for VE against gonorrhoea was 42% (95%CI 6-64 p 0.027). Logistic regression showed that VE against gonorrhoea remained significant (44%, 95%CI 9-65 p 0.020) after adjusting for some factors that might have a potential influence on VE or those with significant unbalanced distributions between cases and controls at univariable analysis. 4CMenB vaccination is associated with lower risk of gonorrhoea in the setting of MSM living with HIV with a previous STI. |
36,728,229 | Doravirine Exposure Decreased by Dialysis in a HIV Patient A Grand Round. | The authors report the case of a 66-year-old male patient who was hemodialyzed 3 times per week for chronic renal failure and treated with 100 mg of doravirine once daily in combination with dolutegravir for HIV-1. No dose adjustment is required for doravirine in cases of severe renal injury, but the effect of dialysis on its exposure is poorly understood. Two series of 2 samples were drawn before and after 4-hour hemodialysis and showed an average doravirine concentration decrease of 48.1 ± 6.7%. The effects of hemodialysis were important, contrary to what was expected and has been previously reported. In addition, intraindividual variability was low. Nevertheless, because the concentrations reported were largely above the inhibitory concentration 50 (IC50), no dose adjustment was required. The decrease in doravirine concentration due to hemodialysis observed in this case report was quite significant. Therefore, therapeutic drug monitoring might be recommended in certain patients undergoing doravirine treatment also on hemodialysis. |
36,728,228 | Adverse events and SARS-CoV-2 antibody responses after immunization with sputnik V, ChAdOx1-S and BBIBP-CorV vaccines in people with HIV. | This study describes adverse events following immunization (AEFIs) and the development of SARS-COV-2 antibodies after Sputnik V, AstraZeneca, and Sinopharm COVID-19 vaccination in PWH. N 595 adult PWH at an HIV center in Argentina from March-December 2021 were enrolled. Analysis included participants who received COVID-19 vaccination with Sputnik V, AstraZeneca, and Sinopharm, and did not receive mRNA COVID-19 vaccines. Clinical data, and local or systemic AEFI variables were collected using an online questionnaire after the first dose. Detection of S1-RBD IgG antibodies was performed between days 28-60 after the second dose in a subsample (SARS-CoV-2 IgG chemiluminescent immunoassay, Siemens). A multivariable logistic regression and spearman test were used for analyses. Mean age was 46.1 years (SD 11.8) 70.4% were male and median CD4 T cells count was 659 (500-852) cellsmL. AEFIs were reported in 214 (36.0%) participants. More participants reported AEFIs after Sputnik V (29.4%) and AstraZeneca (47.5%) than Sinopharm (13.9%) (χ2 35.85, p < 0.001). Higher odds of reporting an AEFIs were associated with receiving Sputnik V (aOR 2.90 95% CI 1.40, 6.04 p 0.004) and AstraZeneca (aOR 5.38 95% CI 2.63, 11.01 p < 0.001) compared to Sinopharm. Lower odds were associated with age (aOR 0.97 (95% CI 0.95, 0.99 p < 0.001). Overall, 76 (95.0%) individuals assessed for the presence of SARS-CoV-2 antibody reached S1-RBD IgG antibody titers ≥1 UmL mean titer was 51.3 (SD 51.07) UmL. Higher antibody titers correlated with higher CD4 T cells count (Rho 0.280 p 0.012). Non-mRNA vaccines showed a safety profile and adequate SARS-CoV-2 antibody responses among PWH suggesting adequate protection to SARS-CoV-2. |
36,728,219 | Real world use of dolutegravir two drug regimens. | Since 2015 we prescribed dolutegravir-based two drug regimens (DTG2DR) for 620people (total cohort 3133 (19.8%)). Clinic database search010115-311021. Demographic, tolerability and HIV related data analysed. 620 people identified 561 had complete data. 446 male (79.5%) median age 54y (IQR46, 59). 343 (61.1%) men who have sex with men. 9 people who initiated naïvelyachieved viral suppression (100%). 546552 (99.0%) switched or continued and weresuppressed at data censor. 460552 (83.3%) received dolutegravir-lamivudine(DTG3TC), 74552 (13.4%) received dolutegravir-rilpivirine (DTGRPV) and 18552(3.3%) received dolutegravir-emtricitabine (DTGFTC). 70 (12.5%) switched off DTG2DR (55DTG3TC, 13 DTGRPV, 2 DTGFTC) due to side-effects. 41 episodes of blip(1 off>50 copiesml) occurred in 30 people (5.3%). 1141 on DTG-RPV (n 7 multitablet regimen(MTR), n 4 single tablet regimen (STR)). 2741 DTG-3TC, 341 DTGFTC (n 26 MTR, n 4 STR). 6people (1.1%) failed (confirmed viral load (VL) >200copiesml or persistent low level viraemia (LLV)) (n 4 DTG-3TC STR, n 1 DTG-3TC MTR, n 1 DTG-RPV MTR). Four failures due to LLV, one due to non-adherence andone due to high VL. Resistance tests performed for 56 - mutations detected only inlatter person with high VL failure (on DTG-3TC MTR) who developed triple classresistance. Majority of experience is in DTG3TC stable switch. Minority ofpatients developed side-effects. Low number of virological failures, one developed INIresistance. Viral failure associated with MTR, commensurate with trial data showing nofailure with resistance if DTG3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting. |
36,728,122 | HIV Viral Load Scale-up Among Children and Adolescents Trends in Viral Load Suppression, Sample Type and Processing in 7 PEPFAR Countries, 2015-2018. | HIV-positive children and adolescents face gaps in viral load (VL) testing. To understand trends in pediatricadolescent VL testing, 7 countries collected data from Laboratory Information Management Systems. Results showed increasing proportion of VL tests done through dried blood spot (DBS) and decreased sample rejection rates for DBS compared with plasma, supporting use of DBS VL when skilled phlebotomy is unavailable. |
36,728,048 | HIV Continuum of Care Among People Who Inject Drugs in Iran A Cross-sectional Study. | People living with HIV who inject drugs may have lower access to treatment services. We aimed to assess the HIV continuum of care among people who inject drugs (PWID) in Iran. Data were collected from 2,663 PWID who were recruited via respondent-driven sampling from 11 cities of Iran between June 2019 and March 2020. Participants who tested positive for HIV infection were asked questions to calculate the status of HIV cascade of care. Of 95 PWID living with HIV, 67% were aware of their HIV status, 57% were linked to care service and initiated ART, 49% retained on ART, and only 15% had viral load less than 1,000 copiesml. About half of the PWID diagnosed with HIV ever started ART and less than one in six were virally suppressed. Strategies to improve linkage to ART programs and ART retention may improve HIV care outcomes among PWID in Iran. |
36,727,844 | HIV acquisition prior to entry into formal sex work inference from next-generation viral sequencing. | To infer the timing of HIV acquisition in relation to self-reported events in the sexual life course of adolescent girls and young women (AGYW) who self-identify as female sex workers (FSW) in Mombasa, Kenya. Next-generation viral sequencing of samples of AGYW living with HIV in the Transitions study, a cross-sectional bio-behavioural survey of AGYW aged 14-24 years in Mombasa, Kenya. Dried blood spot (DBS) specimens were collected from study participants (n 37, all FSW). A portion of the HIV pol gene was sequenced using an in-house next-generation sequencing assay for HIV drug resistance mutation genotyping. Estimated time since infection (ETI) was inferred using the HIV EVO web-based tool (httpshiv.biozentrum.unibas.chETI), and data on self-reported events were obtained from the survey. The median ETI among FSW was 3.4 (IQR 1.7, 6.3) years, with a median ETI of 1.5 years prior to entry into formal sex work. We estimated that 74.1% (95% CI 53.7-88.9%) of participants living with HIV and who self-identified as FSW likely acquired HIV prior to self-identification as a sex worker. Findings suggest a large fraction of prevalent HIV infection among AGYW engaged in sex work stems from acquisition prior to entry into formal sex work. Current HIV prevention programs tailored for sex workers may miss key opportunities for HIV prevention as they are designed to reach women after entry into formal sex work, signaling a need for tailored programs to reach high-risk AGYW earlier on in their sexual life course. |
36,727,840 | A prospective 18F-FDG PETCT study of the neurometabolic effects in cocaine use and HIV infection. | HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18F-fluorodeoxyglucose positron emission tomographycomputed tomography (18F-FDG PETCT) in cocaine users with HIV infection. Sixty-three subjects were categorized into groups 36 HIV infected (HIV) and 27 non-HIV infected (HIV-) subjects. Each group was further split into cocaine users (CO) and non-cocaine users (CO-). Of the HIV, half were cocaine users and half were not. Of the HIV-, 14 were cocaine users and 13 were not. 18F-FDG-PET and low dose CT scans were performed on all subjects. Brain glucose metabolism was evaluated by 18F-FDG uptake in the whole brain, cortex, basal ganglia, and cerebellum 120 minutes after injection. ROVER software was used for image analysis and ROI masks were applied via an adaptive threshold system. ANOVA tests and t-tests were performed to assess the respective differences between the four groups. Generally, the HIVCO group (group A) displayed the lowest levels of uptake whereas the HIV-CO- group (group D) showed the highest the HIVCO- and HIV-CO groups (group B and C) showed intermediate levels of activity across the whole brain, cortex, basal ganglia, and cerebellum. HIV infection and cocaine usage were independently associated with a decrease in brain glucose uptake as measured by 18F-FDG PETCT. When combined, positive HIV status and cocaine patients showed the most decreased 18F-FDG uptake. |
36,727,718 | Two Models for Increasing the Scope and Activities of HIV Partner Services Programs Preliminary Findings from the Fast Track Project. | We sought to develop a novel strategy for expanding an existing HIV partner services (PS) model to provide comprehensive sexual health services, including STI testing, a virtual telemedicine visit, and access to immediate start medication (ART, PEP, or PrEP). Fast Track was an NIH-funded implementation science trial in New York City to pilot and refine the new strategy, and examine its feasibility, acceptability, and impact. Over the course of one year, health department staff collaborated with the academic research team to develop Fast Track protocols and workflows, create a cloud-based database to interview and track patients, and train disease intervention specialists (DIS) to deliver the new program. The initial field-based program (Fast Track 1.0) was piloted March-December 2019. A modified telephone-based program (Fast Track 2.0) was developed in response to COVID-19 pandemic constraints and was piloted August 2020 to March 2021. These two pilots demonstrate the feasibility and acceptability of integrating comprehensive sexual health services into HIV PS programs. DIS were successfully trained to conduct comprehensive sexual health visits, and clients reported that the availability of comprehensive sexual health services made them more willing to engage with PS. Key lessons for scale-up include managing collaboration with a licensed provider, navigating technical and technological issues, and challenges in client engagement and retention. The success of this integrated strategy suggests that telehealth visits may be a critical gateway to care engagement for PS clients. This model is an innovative strategy for increasing engagement with HIV testing, prevention, and treatment for underserved populations. |
36,727,653 | Usefulness of dried blood spot samples for monitoring hepatitis C treatment outcome and reinfection among people who inject drugs in a test-and-treat program. | Dried blood spots (DBS) are a reliable tool to diagnose viremic HCV infection. We evaluated the clinical performance of a DBS-based molecular assay for the assessment of cure and reinfection after on-site treatment at a harm reduction centre (HRC). Genotyping from DBS samples was also assessed to discriminate reinfection from treatment failure. People who inject drugs (PWID) from an ongoing microelimination pilot at the largest HRC in Barcelona were included in the study. HCV-RNA detection from DBS collected after treatment (with follow-up at 12, 36 and 60 weeks) was compared with a molecular point-of-care test using finger-stick blood (GeneXpert). Baseline and follow-up DBS samples were genotyped by NS5B sequencing or commercial real-time PCR. Among treated patients, 193 follow-up DBS samples were tested. The DBS-based assay showed 100% specificity (129129), and sensitivity ranged from 84.4% to 96.1% according to different viral load cut-offs (from detectable to 3000 IUmL). Sensitivity as test of cure (follow-up 12) ranged from 85.1 to 97.4%. Among the 64 patients with recurrent viremia, 10.9% had low viral loads (≤1000 IUmL) HCV genotyping allowed us to classify 73.5% of viremic cases either as reinfection or as treatment failure. DBS samples are useful to assess cure and differentiate reinfection from relapse after HCV antiviral treatment in the real world, facilitating decentralization of treatment and post-treatment follow-up in PWID. However, a fraction of patients presented with low viral loads, limiting viremia detection and genotyping in DBS and, therefore, repeat testing is recommended. This article is protected by copyright. All rights reserved. |
36,727,646 | Treatment with integrase inhibitors alters SARS-CoV-2 neutralization levels measured with HIV-based pseudotypes in people living with HIV. | The presence of neutralizing antibodies (NAbs) is a major correlate of protection for SARS-CoV-2 infection. Thus, different in vitro pseudoviruses-based assays have been described to detect NAbs against SARS-CoV-2. However, the determination of NAbs against SARS-CoV-2 in people living with HIV (PLWH) through HIV-based pseudoparticles could be influenced by cross-neutralization activity or treatment, impeding accurate titration of NAbs. Two assays were compared using replication-defective HIV or VSV-based particles pseudotyped with SARS-CoV-2 spike to measure NAbs in COVID-19-recovered and COVID-19-naïve PLWH. The assay based on HIV-pseudoparticles displayed neutralization activity in all COVID-19-recovered PLWH with a median neutralizing titer 50 (NT50) of 1417.0 (interquartile range IQR 450.3 - 3284.0), but also in 67% of COVID-19-naïve PLWH (NT50 631.5, IQR 16.0 - 1535.0). Regarding VSV-pseudoparticles system, no neutralization was observed in COVID-19-naïve PLWH as expected, whereas in comparison with HIV-pseudoparticles assay lower neutralization titers were measured in 75% COVID-19-recovered PLWH (NT50 100.5 IQR 20.5 - 1353.0). Treatment with integrase inhibitors was associated with inaccurate increase in neutralization titers when HIV-based pseudoparticles were used. IgG purification and consequent elimination of drugs from samples avoided the interference with retroviral cycle and corrected the lack of specificity observed in HIV-pseudotyped assay. This study shows methodological alternatives based on pseudoviruses systems to determine specific SARS-CoV-2 neutralization titers in PLWH. This article is protected by copyright. All rights reserved. |
36,727,597 | Uptake of medical male circumcision with household-based testing, and the association of traditional male circumcision and HIV infection. | Voluntary medical male circumcision (VMMC) is an important component of combination HIV prevention. Inclusion of traditionally circumcised HIV negative men in VMMC uptake campaigns may be important if traditional male circumcision is less protective against HIV acquisition than VMMC. We used data from the HPTN 071 (PopART) study. This cluster-randomized trial assessed the impact of a combination prevention package on population-level HIV incidence in 21 study communities in Zambia and South Africa.We evaluated uptake of VMMC, using a two-stage analysis approach and used discrete-time survival analysis to evaluate the association between the types of male circumcision and HIV incidence. 10,803 HIV-negative men with self-reported circumcision status were included in this study. At baseline, 56% reported being uncircumcised, 26% traditionally circumcised and 18% were medically circumcised. During the PopART intervention, 11% of uncircumcised men reported uptake of medical male circumcision. We found no significant difference in the uptake of VMMC in communities receiving the PopART intervention package and standard of care (adj rate ratio1·10 (95% CI 0·82, 1·50, P 0·48)). The rate of HIV acquisition for medically circumcised men was 70% lower than for those who were uncircumcised adjHR0·30 (95% CI 0·16 to 0·55 p < 0·0001). There was no difference in rate of HIV acquisition for traditionally circumcised men compared to those uncircumcised adjHR 0·84 (95% CI 0·54, 1·31 P 0·45). Household-based delivery of HIV testing followed by referral for medical male circumcision did not result in substantial VMMC uptake. Traditional circumcision is not associated with lower risk of HIV acquisition. |
36,727,571 | Transient viral rebound in children with perinatally acquired HIV-1 induces a unique soluble immunometabolic signature associated with decreased CD4CD8 ratio. | To determine by multi-omic analysis changes in metabolites, lipids and proteins as consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV). Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copiesml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS and LC-qTOF-MS. Comparing pre- and post-tVR time-points, HIV-1-children with tVR (n5) showed a trend to a decrease in ratio CD4CD8 (p0.08) but no significant differences were observed in plasma metabolites, lipids or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n9), paired by sex, age and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites and 2 lipids showed significant differences (p<0.05) serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 500 (TG500) and diacylglyceride 341 (DG341) were up-regulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid and D-sucrose downregulated on post-tVR time-point compared to reference group. Ratio CD4CD8 correlated with apolipoprotein A-II, DG341 and methionine (p0.004ρ0.71, p0.016ρ-0.63 and p0.032ρ-0.57, respectively). Nadir CD4 correlated inversely with kininogen-1 (p0.022ρ-0.60) and positively with D-sucrose (p0.001ρ0.77). tVR followed by suppression implies changes in soluble proteins, lipids and metabolites that correlate with immunological parameters, mainly ratio CD4CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression. |
36,727,526 | Kaposi sarcoma-associated herpesvirus, HIV-1 and Kaposi sarcoma risk in black South Africans diagnosed with cancer during antiretroviral treatment rollout. | Kaposi sarcoma-associated herpesvirus (KSHV) causes Kaposi sarcoma (KS). The risk of KS is amplified in HIV-immunosuppressed individuals and antiretroviral therapy (ART) reduces KS incidence. Reliable data on the relationship between these factors are lacking in Africa. We used questionnaires and serum from 7886 black South Africans (18-74 years) with incident cancer, recruited between 1995 and 2016. ART rollout started in 2004. We measured associations between KS, HIV-1 and KSHV before and after ART rollout. We measured seropositivity to HIV-1, KSHV latency-associated nuclear antigen (LANA) and glycoprotein (K8.1) and calculated case-control-adjusted odds ratios (OR |
36,727,169 | Contraceptive Continuation and Experiences Obtaining Implant and IUD Removal Among Women Randomized to Use Injectable Contraception, Levonorgestrel Implant, and Copper IUD in South Africa and Zambia. | Few longitudinal studies have measured contraceptive continuation past one year in sub-Saharan Africa. We surveyed 674 women who had been randomized to receive the three-month intramuscular contraceptive injectable (DMPA-IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in-depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan-Meier estimates and assessed factors associated with discontinuation using Cox-proportional hazards models. The LNG implant continuation rate over the maximum 44-month study period was 60 percent, while rates for the copper IUD and DMPA-IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock-outs. Most implant and IUD users who sought removal were able to access services however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested. |
36,726,992 | Impact of SIV infection on mycobacterial lipid-reactive T cell responses in Bacillus Calmette-Guérin (BCG) inoculated macaques. | Although BCG vaccine protects infants from tuberculosis (TB), it has limited efficacy in adults against pulmonary TB. Further, HIV coinfection significantly increases the risk of developing active TB. In the lack of defined correlates of protection in TB disease, it is essential to explore immune responses beyond conventional CD4 T cells to gain a better understanding of the mechanisms of TB immunity. Here, we evaluated unconventional lipid-reactive T cell responses in cynomolgus macaques following aerosol BCG inoculation and examined the impact of subsequent SIV infection on these responses. Immune responses to cellular lipids of Prior to BCG inoculation, innate-like IFN-γ responses to mycobacterial lipids were observed in T cells. Aerosol BCG exposure induced an early increase in frequencies of BAL γδT cells, a dominant subset of lipid-reactive T cells, along with enhanced IL-7R and CXCR3 expression. Further, BCG exposure stimulated greater IFN-γ responses to mycobacterial lipids in peripheral blood and BAL, suggesting the induction of systemic and local Th1-type response in lipid-reactive T cells. Subsequent SIV infection resulted in a significant loss of IL-7R expression on blood and BAL γδT cells. Additionally, IFN-γ responses of mycobacterial lipid-reactive T cells in BAL fluid were significantly lower in SIV-infected macaques, while perforin production was maintained through chronic SIV infection. Overall, these data suggest that despite SIV-induced decline in IL-7R expression and IFN-γ production by mycobacterial lipid-reactive T cells, their cytolytic potential is maintained. A deeper understanding of anti-mycobacterial lipid-reactive T cell functions may inform novel approaches to enhance TB control in individuals with or without HIV infection. |
36,726,972 | null | Most cervicovaginal microbiome-immunology studies to date have relied on 16S rDNA microbial profiling which does not resolve the molecular subgroups of |
36,726,933 | Extranodal Involvement of the Anorectal Region in an HIV-Positive Patient With Plasmablastic Lymphoma A Case Report. | Plasmablastic lymphoma (PbL) is a rare type of aggressive B-cell malignancy that has an extremely poor prognosis without chemotherapeutic treatment, requiring a high degree of suspicion for an early and accurate diagnosis. It has been classically described in patients infected with the human immunodeficiency virus (HIV). However, it accounts for only 2.6% of acquired immunodeficiency syndrome (AIDS)-related lymphomas. Extranodal involvement is most commonly seen within the oral cavity (44%). Involvement of the gastrointestinal tract (14%) is rare and can often be confused with other malignancies with plasmablastic features. We present a rare case of PbL in a 55-year-old male with HIV-AIDS (CD4 (cluster of differentiation 4) cell count of 128), who presented for evaluation of incidentally detected multiple liver masses and lytic lesions in the ribs. Further workup revealed evidence of a lesion with increased uptake in the anorectal region with fine needle aspiration (FNA) biopsy identifying the lesion as plasmablastic lymphoma. |
36,726,790 | Cervical Cancer Screening Service Utilization and Associated Factors Among Women Living With HIV Receiving Anti-Retroviral Therapy at Adama Hospital Medical College, Ethiopia. | Cervical cancer is the second highest cause of cancer-related mortality in the world, and it is one of the top 20 causes of mortality in Ethiopia. Even though cervical cancer is more common among women living with HIV, the utilization of cervical cancer screening services remains low in Ethiopia. This study aimed to assess cervical cancer screening service utilization and associated factors among women living with HIV receiving anti-retroviral therapy at Adama Hospital Medical College, Ethiopia. An institution-based cross-sectional study was conducted among a sample of 304 women living with HIV from 1st-30th June 2022. Data were collected using an interviewer-administered questionnaire. The data were entered into Epi info version 7 and exported to SPSS version 25 for analysis. Bi-variable logistic regression analysis was used to identify candidate variables at The magnitude of cervical cancer screening service utilization was 26.9% (95% CI 22.0, 32.6). Being a government employee (AOR 8.09, 95% CI 1.5, 41.19), having a family history of cervical cancer (AOR 3.4, 95% CI 1.02, 11.9), being aware of cervical cancer screening (AOR 3.75, 95% CI 2.11, 14.7), having a history of sexually transmitted infection (AOR 3.14, 95% CI 1.95, 10.2), and heard about cervical cancer (AOR 2.6, 95% CI 1.05, 6.41) were associated with cervical cancer screening service utilization. The magnitude of cervical cancer screening service utilization was low. It was associated with occupation status, family history of cervical cancer, awareness about cervical cancer screening, history of STI, and ever heard about cervical cancer. Thus, to maximize utilization, health education programs and other multidisciplinary strategies had to be implemented. |
36,726,550 | Monkeypox Vaccination Strategy and Missed Opportunities in STI and HIV Prevention An Urban Sexual Health Clinics Experience During a Public Health Emergency. | Among individuals presenting for monkeypox vaccination, transition from an opt-out protocol for sexually transmitted infection (STI) and HIV risk assessment and testing to an opt-in protocol was associated with a substantial increase in missed opportunities for HIV pre-exposure prophylaxis and STI testing at an ambulatory sexual health clinic. |
36,726,547 | Sex and Race Disparities in Mortality and Years of Potential Life Lost Among People With HIV A 21-Year Observational Cohort Study. | Since the availability of antiretroviral therapy, mortality rates among people with HIV (PWH) have decreased however, this does not quantify premature deaths among PWH, and disparities persist. We examined all-cause and premature mortality among PWH receiving care at the Vanderbilt Comprehensive Care Clinic from January 1998 to December 2018. Mortality rates were compared by demographic and clinical factors, and adjusted incidence rate ratios (aIRRs) were calculated using multivariable Poisson regression. For individuals who died, age-adjusted years of potential life lost (aYPLL) per total person-years living with HIV were calculated from US sex-specific life tables, and sex and race differences were examined using multivariable linear regression. Among 6531 individuals (51% non-Hispanic NH White race, 40% NH Black race, 21% cis-gender women, 78% cis-gender men) included, 956 (14.6%) died. In adjusted analysis, PWH alive in the most recent calendar era (2014-2018) had decreased risk of mortality compared with those in the earliest calendar era (1998-2003 aIRR, 0.22 95% CI, 0.17-0.29), and women had increased risk of death compared with men (aIRR, 1.31 95% CI, 1.12-1.54). Of those who died, Black women had the highest aYPLL (aIRR, 592.5 95% CI, 588.4-596.6), followed by Black men (aIRR, 470.7 95% CI, 468.4-472.9), White women (aIRR, 411.5 95% CI, 405.6-417.4), then White men (aIRR, 308.6 95% CI, 308.0-309.2). In adjusted models, higher YPLL remained associated with NH Black race and cis-gender women, regardless of HIV risk factor. Despite marked improvement over time, sex disparities in mortality as well as sex and race disparities in YPLL remained among PWH in this cohort. |
36,726,540 | Cannabis Use Is Associated With Decreased Antiretroviral Therapy Adherence Among Older Adults With HIV. | Conflicting evidence exists on the impact of cannabis use on antiretroviral therapy (ART) adherence among people with human immunodeficiency virus (PWH). We leveraged data collected among older PWH to characterize longitudinal associations between cannabis use and ART adherence. AIDS Clinical Trials Group (ACTG) A5322 study participants were categorized as <100% (≥1 missed dose in past 7 days) or 100% (no missed doses) ART adherent. Participants self-reported current (past month), intermittent (past year but not past month), and no cannabis (in past year) use at each study visit. Generalized linear models using generalized estimating equations were fit and inverse probability weighting was used to adjust for time-varying confounders and loss to follow-up. Among 1011 participants (median age, 51 years), 18% reported current, 6% intermittent, and 76% no cannabis use at baseline 88% reported 100% ART adherence. Current cannabis users were more likely to be <100% adherent than nonusers (adjusted risk ratio aRR, 1.53 95% CI, 1.11-2.10). There was no association between ART adherence and current versus intermittent (aRR, 1.39 95% CI, .85-2.28) or intermittent versus no cannabis use (aRR, 1.04 95% CI, .62-1.73). Among a cohort of older PWH, current cannabis users had a higher risk of <100% ART adherence compared to nonusers. These findings have important clinical implications as suboptimal ART adherence is associated with ART drug resistance, virologic failure, and elevated risk for mortality. Further research is needed to elucidate the mechanisms by which cannabis use decreases ART adherence in older PWH and to advance the development of more efficacious methods to mitigate nonadherence in this vulnerable population. |
36,726,539 | Treatment Success Following Standard Antibiotic Treatment for Bacterial Vaginosis Is Not Associated With Pretreatment Genital Immune or Microbial Parameters. | Bacterial vaginosis (BV) is a proinflammatory genital condition associated with adverse reproductive health outcomes, including increased HIV incidence. However, BV recurrence rates are high after standard antibiotic treatment. While the composition of the vaginal microbiota before BV treatment may be linked to BV recurrence, it is unclear whether the preceding genital immune milieu is predictive of treatment success. Here we assessed whether baseline vaginal soluble immune factors or the composition of the vaginal microbiota predicted treatment success 1 month after metronidazole treatment in 2 separate cohorts of women with BV, 1 in the United States and 1 in Kenya samples within 48 hours of BV treatment were also available for the US cohort. Neither soluble immune factors nor the composition of the vaginal microbiota before BV treatment was associated with treatment response in either cohort. In the US cohort, although the absolute abundances of key vaginal bacterial taxa pretreatment were not associated with treatment response, participants with sustained BV clearance had a more pronounced reduction in the absolute abundance of Pretreatment immune and microbial parameters were not predictive of BV treatment success in these clinical cohorts. |
36,726,538 | Partial-Oral Antibiotic Therapy for Bone and Joint Infections in People With Recent Injection Drug Use. | Limited outcome data exist regarding partial-oral antibiotic therapy, defined as oral antibiotics as part of a patients treatment, for bone and joint infections (BJIs) in people who inject drugs (PWID). We conducted a retrospective study of all PWID reporting drug use within 3 months and BJIs requiring ≥6 weeks of antibiotics in an urban safety-net hospital between February 1, 2019, and February 1, 2021. Treatment outcomes were assessed by chart review. Rates of failure, defined as death, symptoms, or signs concerning for worsening or recurrent infections, were assessed 90 and 180 days after completion of antibiotics. Univariate logistic regression was used to explore the association between covariates and failure. Of 705 patients with BJI, 88 (13%) were PWID. Eighty-six patients were included in the final cohort. Forty-four (51%) were homeless, 50 (58%) had spine infection, 68 (79%) had surgery, and 32 of 68 (47%) had postoperatively retained hardware. Twelve (14%) of 86 patients received exclusively intravenous (IV) antibiotics, and 74 (86%) received partial-oral antibiotics. Twelve (14%) of 86 patients had patient-directed discharge. In those who received partial-oral antibiotics, the failure rate was 20% at 90 days and 21% at 180 days after completion of intended treatment. Discharge to a medical respite and follow-up with infectious diseases (ID) or surgery were negatively associated with odds of failure. Partial-oral treatment of BJI in PWID was a common practice and often successful when paired with medical respite and follow-up with ID or surgery. |
36,726,536 | Phenotypic Profile of | Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is a frequent complication of cotreatment for TB and human immunodeficiency virus (HIV)-1. We characterized We examined the role of CD4 T-cell transcription factors in a murine model of mycobacterial IRIS. In humans, we used a longitudinal study design to compare the magnitude of antiretroviral therapy, activation, transcription factor profile, and cytotoxic potential of Mtb-specific CD4 T cells between TB-IRIS ( In the murine model, CD4 T-cell expression of Eomesodermin (Eomes), but not Tbet, was associated with experimentally induced IRIS. In patients, TB-IRIS onset was associated with the expansion of Mtb-specific IFNγ Although the murine model of |
36,726,492 | Drug Resistance of | This study investigated drug-resistant tuberculosis (DR-TB) in the Yi ethnic group. The study was designed to identify risk factors for DR-TB and its relationship with HIVAIDS. To establish the resistance to antituberculosis drugs, whole-genome sequencing (WGS) was performed using culture-positive |
36,726,288 | Providing HIV pre-exposure prophylaxis to men who have sex with men and transgender women in hospitals and community-led clinics in Thailand acceptance, patterns of use, trends in risk behaviors, and HIV incidence. | From May 2015 to June 2018, we conducted a PrEP demonstration project at two hospitals and four community-led clinics in Bangkok and Pattaya. HIV-negative, MSM and TGW aged ≥18 years old, reporting sex without a condom, were offered daily PrEP. Participants received HIV testing and completed a computer-based questionnaire at enrollment, 6 and 12 months. We collected self-reported PrEP adherence at months 1, 3, 6, 9, and 12. We used logistic regression to determine factors associated with the decision to take PrEP and calculated HIV incidence among baseline HIV-negative participants. Of 803 participants enrolled, 349 (43.5%) started PrEP. Participants were more likely to start PrEP if they were sex workers, had moderate or high self-perceived risk of HIV, or a high PrEP-knowledge score. Participants used PrEP for a median of 6.1 months. Reported condom use increased and the number of sex partners decreased during follow-up regardless of PrEP use. Six participants not-taking PrEP acquired HIV (HIV incidence 2.2 per 100 person-years), and five taking PrEP acquired HIV (HIV incidence 2.1 per 100 person-years). All five reported taking <4 pills the weeks before study visits. |
36,726,239 | Lower anti-mullerian hormone levels are associated with HIV in reproductive age women and shorter leukocyte telomere length among late reproductive age women. | We sought to better understand factors associated with ovarian aging in women living with HIV (WLWH). HIV has been associated with diminished fertility, younger age at menopause, and shorter leukocyte telomere length (LTL), a marker of cellular aging. We herein examine cross-sectional and longitudinal associations between LTL, Anti-Mullerian hormone (AMH), and HIV. We included WLWH and HIV-negative women 12-50 years of age in the CARMA cohort with ≥ 1 study visit(s). LTL and AMH were measured by qPCR and ELISA, respectively. Women were analysed in peak reproductive (<35 years) vs. late reproductive (≥35 years) life phases. Using multivariable mixed-effect linear or logistic regressions, we assessed factors associated with AMH and ΔAMHyear while adjusting for relevant confounders. WLWH had shorter LTL and lower AMH levels compared to HIV-negative controls despite being of similar age. After adjusting for relevant factors, HIV was associated with 20% lower AMH levels in women <35 years and shorter LTL was associated with AMH levels below 2 ngml among women ≥35 years. Longitudinally, ΔAMHyear was largely related to initial AMH level among older women, and to age in younger women. Factors associated with AMH change across womens reproductive lifespan. Lower AMH among peak reproductive aged WLWH suggests that HIV may have an initial detrimental effect on ovarian reserve, an observation that may warrant counselling around pregnancy planning. In women ≥35, the association between shorter LTL and lower AMH suggests that the immune and reproductive aging connections are more important in this age group. |
36,726,211 | The Impact of Human Immunodeficiency Virus and Menopause on Bone Mineral Density A Longitudinal Study of Urban-Dwelling South African Women. | An estimated 25% of South African women live with human immunodeficiency virus (HIV). Antiretroviral therapy roll-out has improved life expectancy, so many more women now reach menopause. We aimed to quantify changes in bone mineral density (BMD) during the menopausal transition in urban-dwelling South African women with and without HIV and determine whether HIV infection modified the effect of menopause on BMD changes. A 5-year population-based longitudinal study recruited women aged 40-60 years residing in Soweto and collected demographic and clinical data, including HIV status, anthropometry, and BMD, at baseline and at 5-year follow-up. All women were staged as pre-, peri-, or postmenopausal at both time points. Multivariable linear regression assessed relationships and interactions between HIV infection, menopause, and change in BMD. At baseline, 450 women had mean age 49.5 (SD 5.7) years, 65 (14.4%) had HIV, and 140 (31.1%), 119 (26.4%), and 191 (42.4%) were pre-, peri-, and postmenopausal, respectively 34205 (13.6%) women ≥50 years had a total hip (TH) or lumbar spine (LS) T-score ≤ -2.5. At follow-up 38 (8.4%), 84 (18.7%), and 328 (72.9%) were pre-, peri-, and postmenopausal. Those with HIV at baseline lost more total body (TB) BMD (mean difference -0.013 95% confidence interval -0.026, -0.001 gcm |
36,726,113 | Prevalence, severity, and associated factors of depression in newly diagnosed people living with HIV in Kilimanjaro, Tanzania a cross-sectional study. | Depression is particularly common among people living with Human Immunodeficiency Virus (HIV), with some studies showing a prevalence of depression three times higher among people living with HIV as compared to the general public. The stress associated with being diagnosed with HIV can be quite impactful, including concerns about ones long-term health, stigma, and the burden of long-term treatment. Therefore, it is common for a new HIV diagnosis to contribute to the onset of depressive symptoms. The objective of this study was to determine the prevalence and severity of depression, and its associated factors in people diagnosed with HIV within the past 12 months. We conducted a cross-sectional survey with patients newly diagnosed with HIV at three hospitals in the Kilimanjaro region of Tanzania utilizing a locally validated version of the Patient Health Questionnaire-9 (PHQ-9) as a screener for depression, the Demographic Health Survey (SES-DHS8) for socio-demographic characteristics, and the Duke-UNC Functional Social Support Questionnaire (FSSQ) to assess perceived social support. We enrolled 272 participants between September and December 2020, diagnosed with HIV within the past 12 months. Analysis of Co-variance (ANCOVA) and Bonferroni post-hoc analysis were used to determine associations of sociodemographic variables with the dependent variable of depression. Overall prevalence of depression in our sample was 41%, including 54 participants (20%) with moderate symptoms, 42 (15%) with moderately severe symptoms, and 16 (6%) with severe symptoms. Severity was highest in participants diagnosed with HIV less than 1 month ago. An ANCOVA model (overall F 4.72, p < 0.001) assessing factors associated with greater depression severity revealed significant effects of study site (F 7.6, p < 0.001), female gender (F 5.11, p 0.02), and less time since HIV diagnosis (F 12.3, p < 0.001). The study demonstrates very high prevalence of depression among people living with HIV in this setting, particularly among those newly diagnosed, female participants, and those seen at the larger regional referral hospital. Integration of mental health screening and interventions into CTC care is vital in the first visits following a positive test result and may be tailored to meet the needs of patients at highest risk for developing symptoms of depression. |
36,725,808 | HIV Knowledge among African Americans Living with HIV in the Rural South Implications for Improving HIV Prevention and Care Outcomes. | This study examines the HIV knowledge of people living with HIV (PLWH) and its implications for improved healthcare outcomes. The study design was a descriptive cross-sectional study, and a total of 41 PLWH were recruited from a larger faith-based anti-stigma study. Data was collected using a semi-structured self-administered questionnaire and analyzed using SAS. In addition, a literature review was conducted using search engines to gauge existing literature from 2013 to 2022 in areas of HIV knowledge and healthcare outcomes among PLWH. The 41 PLWH enrolled consisted of 51% males and 49% females. Sixteen (39%) were aged ≥ 51 years, 17 (41%) had been living with HIV for > 10 years, 15 (37%) had < high school diploma, and 100% were currently in HIV care. HIV knowledge scores were below average for 20 (49%) of the PLWH. Substantial knowledge deficits were noted in areas of HIV transmission and risk reduction strategies. Lower scores were not significantly associated with the participants gender, education level, or length of time being HIV-infected. The results of the literature review showed limited research in this area. The study and literature review results show that HIV knowledge and health literacy may contribute to racial disparities in retention in care leading to poor health outcomes. Healthcare providers and health facilities in rural areas should be equipped with culturally tailored HIV educational tools to strengthen ongoing care for PLWH, foster patient-provider relationships, and eliminate internalized stigma detrimental to improved healthcare outcomes among PLWH. |
36,725,084 | First-line nivolumab plus ipilimumab for metastatic non-small cell lung cancer, including patients with ECOG performance status 2 and other special populations CheckMate 817. | CheckMate 817, a phase 3B study, evaluated flat-dose nivolumab plus weight-based ipilimumab in patients with metastatic non-small cell lung cancer (NSCLC). Here, in this research, we report on first-line treatment in patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 (cohort A) and special populations (cohort A1 ECOG PS 2 or ECOG PS 0-1 with untreated brain metastases, renal impairment, hepatic impairment, or controlled HIV infection). Cohorts A and A1 received nivolumab 240 mg every 2 weeks plus ipilimumab 1 mgkg every 6 weeks. The primary endpoint was the incidence of grade 3-4 and grade 5 immune-mediated adverse events (IMAEs adverse events (AEs) deemed potentially immune-related, occurring <100 days of last dose, and treated with immune-modulating medication (except endocrine events)) and treatment-related select AEs (treatment-related AEs with potential immunological etiology requiring frequent monitoringintervention, reported between first dose and 30 days after the last dose) in cohort A efficacy endpoints were secondaryexploratory. In cohort A1, safetyefficacy assessment was exploratory. The most common grade 3-4 IMAEs were pneumonitis (5.1%), diarrheacolitis (4.9%), and hepatitis (4.6%) in cohort A (N391) and diarrheacolitis (3.5%), hepatitis (3.5%), and rash (3.0%) in cohort A1 (N198). The most common grade 3-4 treatment-related select AEs were hepatic (5.9%), gastrointestinal (4.9%), and pulmonary (4.6%) events in cohort A and gastrointestinal (4.0%), skin (3.5%), and endocrine (3.0%) events in cohort A1. No grade 5 IMAEs or treatment-related select AEs occurred. Treatment-related deaths occurred in 4 (1.0%) and 3 (1.5%) patients in cohorts A and A1, respectively. Three-year overall survival (OS) rates were 33.7% and 20.5%, respectively. Flat-dose nivolumab plus weight-based ipilimumab was associated with manageable safety and durable efficacy in cohort A, consistent with data from phase 3 metastatic NSCLC studies. Special populations of cohort A1 including patients with ECOG PS 2 or ECOG PS 0-1 with untreated brain metastases had manageable treatment-related toxicity and clinically meaningful 3-year OS rate. NCT02869789. |
36,724,857 | Improving Cancer Care in People Living with HIV A Qualitative Study of Provider Knowledge, Attitudes, and Practice. | Cancer is now the leading cause of non-AIDS death in the U.S. HIV population. People living with HIV (PLWH) are known to have lower cancer treatment rates and worse cancer outcomes. Disparate cancer treatment is driven by health system, patient, and clinician factors. Little attention has been given to the factors oncologists consider when making cancer treatment recommendations to PLWH. This study sought to examine oncologists knowledge, attitudes, and practices that influence cancer treatment decision-making. This study used qualitative methods to explore oncologists treatment decision-making process for PLWH and cancer. The sample included 25 radiation, medical, and surgical oncologists from two academic centers and five community practices. The interview domains were developed from the Andersen Healthcare Utilization Model, the Health Belief Model, and the PEN-3 Model, as well as our prior survey research. This study describes elements of cancer treatment decision-making for PLWH. Oncologists highlighted the need for formal HIV education to support cancer treatment. One main concern with patient-provider interactions pertained to maintaining patient confidentiality during clinical encounters. Lastly, the importance of multidisciplinary care amongst healthcare providers allowed oncologists to facilitate both cancer care and logistical support. As cancer becomes an increasingly common cause of death among PLWH, it is critical to understand the drivers of the observed disparities in cancer treatment. To our knowledge, this is the first qualitative study to describe oncologists knowledge, attitudes, and practices towards patients who have a comorbid diagnosis of HIV and cancer. Several themes for future interventions emerge, including HIV training for cancer care providers, fostering interdisciplinary collaboration, enhancing HIV education for oncology learners and clinicians, and minimizing implicit bias. |
36,724,437 | Tuberculosis Preventative Therapy Initiation and Completion Among Adolescents and Young Adults Living With HIV in Kenya. | Tuberculosis is the leading cause of death among adolescents and young adults living with HIV (YWHIV) and their heightened risk warrants deeper understanding of utilization of tuberculosis-prevention measures within HIV care. Retrospective study using clinic surveys and medical record data from 86 Kenyan HIV clinics. Clinic surveys obtained information on tuberculosis preventive therapy (TPT) services. Medical records of YWHIV were abstracted. Bivariate and multivariate analyses used generalized linear models to determine individual-level and clinic-level cofactors of TPT initiation and completion. Among 10,328 eligible YWHIV, 4337 (42.0%) initiated TPT. Of 3295 with ≥6 months follow-up, 1774 (53.8%) completed TPT. A lower patient-to-staff ratio was a clinic-level cofactor of TPT initiation ( P 0.044) and completion ( P 0.004) designated adolescent areas were associated with TPT initiation prevalence ratio 2.05 95% confidence interval (CI) 1.46 to -2.88. Individual cofactors of TPT initiation included younger age at HIV-care enrollment relative risk (RR) 0.85 (95% CI 0.80 to 0.90) and antiretroviral therapy (ART) duration 1-2 vs. <1 year RR 1.31 (95% CI 1.18 to 1.45). TPT completion was associated with younger age RR 0.91 (95% CI 0.85 to 0.98) and ART duration 2-5 vs. <1 year RR 1.27 (95% CI 1.03 to 1.57). In multivariate models, TPT initiation was associated with younger age and ART duration 1-2 vs. 1 year adjusted RR 1.30 (95% CI 1.16 to 1.46) and TPT completion with ART duration 2-5 vs. 1 year adjusted RR 1.23 (95% CI 0.99 to 1.52). Over half of YWHIV did not initiate and >40% did not complete TPT, with distinct clinic-level and individual-level cofactors. Approaches to enhance adolescent-friendly infrastructure and support older YWHIV are necessary to improve TPT use. |
36,724,434 | Suboptimal lopinavir exposure in infants on rifampicin treatment receiving double-dosed or semi-superboosted lopinavirritonavir time for a change. | While super-boosted lopinavirritonavir (LPVr ratio 44 instead of 41) is recommended for infants living with HIV and receiving concomitant rifampicin, in clinical practice many different LPVr dosing strategies are applied due to poor availability of paediatric separate ritonavir formulations needed to super-boost. We evaluated LPV pharmacokinetics in infants with HIV receiving LPVr dosed according to local guidelines in various sub-Saharan African countries with or without rifampicin-based tuberculosis (TB)-treatment. This was a 2-arm pharmacokinetic sub-study nested within the EMPIRICAL trial (NCT03915366). Infants aged 1-12 months recruited into the main study were administered LPVr according to local guidelines and drug availability either with or without rifampicin-based TB-treatment during rifampicin co-treatment they received double-dosed (ratio 82) or semi-superboosted LPVr (adding a ritonavir 100mg crushed tablet to the evening LPVr dose). Six blood samples were taken over 12 hours after intake of LPVr. In total, 1416 included infants had evaluable pharmacokinetic curves 914 had rifampicin co-treatment (5 received double-dosed and 4 semi-superboosted LPVr). The median (IQR) age was 6.4 months (5.4-9.8), weight 6.0kg (5.2-6.8) and 1014 were male. Of those receiving rifampicin, 69 (67%) infants had LPV Ctrough <1.0mgL compared to 15 (20%) in the control arm. LPV apparent oral clearance was 3.3-fold higher for infants receiving rifampicin. Double-dosed or semi-superboosted LPVr for infants aged 1-12 months receiving rifampicin resulted in substantial proportions of subtherapeutic LPV levels. There is an urgent need for data on alternative antiretroviral regimens in infants with HIVTB co-infection, including twice-daily dolutegravir. |
36,724,259 | A virus-induced circular RNA maintains latent infection of Kaposis sarcoma herpesvirus. | Non-coding RNAs (ncRNAs) play important roles in host-pathogen interactions oncogenic viruses like Kaposis sarcoma herpesvirus (KSHV) employ ncRNAs to establish a latent reservoir and persist for the life of the host. We previously reported that KSHV infection alters a novel class of RNA, circular RNAs (circRNAs). CircRNAs are alternative splicing isoforms and regulate gene expression, but their importance in infection is largely unknown. Here, we showed that a human circRNA, hsacirc0001400, is induced by various pathogenic viruses, namely KSHV, Epstein-Barr virus, and human cytomegalovirus. The induction of circRNAs including circ0001400 by KSHV is co-transcriptionally regulated, likely at splicing. Consistently, screening for circ0001400-interacting proteins identified a splicing factor, PNISR. Functional studies using infected primary endothelial cells revealed that circ0001400 inhibits KSHV lytic transcription and virus production. Simultaneously, the circRNA promoted cell cycle, inhibited apoptosis, and induced immune genes. RNA-pull down assays identified transcripts interacting with circ0001400, including |
36,724,179 | High-throughput saturation mutagenesis generates a high-affinity antibody against SARS-CoV-2 variants using protein surface display assay on a human cell. | As new mutations continue to emerge, the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus to evade the human immune system and neutralizing antibodies remains a huge challenge for vaccine development and antibody research. The majority of neutralizing antibodies have reduced or lost activity against SARS-CoV-2 variants. In this study, we reported a novel protein surface display system on a mammalian cell for obtaining a higher-affinity antibody in high-throughput manner. Using a saturation mutagenesis strategy through integrating microarray-based oligonucleotide synthesis and single-cell screening assay, we generated a group of new antibodies against diverse prevalent SARS-CoV-2 variants through high-throughput screening the human antibody REGN10987 within 2 weeks. The affinity of those optimized antibodies to seven prevalent mutants was greatly improved, and the EC50 values were no higher than 5 ngmL. These results demonstrate the robustness of our screening system in the rapid generation of an antibody with higher affinity against a new SARS-CoV-2 variant, and provides a potential application to other protein molecular interactions. |
36,723,955 | DNAJB8 facilitates autophagic-lysosomal degradation of viral Vif protein and restricts HIV-1 virion infectivity by rescuing APOBEC3G expression in host cells. | HSP40DNAJ family of proteins is the most diverse chaperone family, comprising about 49 isoforms in humans. Several reports have demonstrated the functional role of a few of these isoforms in the pathogenesis of various viruses, including HIV-1. Our earlier study has shown that several isoforms of HSP40 get significantly modulated at the mRNA level during HIV-1 infection in T cells. To explore the biological role of these significantly modulated isoforms, we analyzed their effect on HIV-1 gene expression and virus production using knockdown and overexpression studies. Among these isoforms, DNAJA3, DNAJB1, DNAJB7, DNAJC4, DNAJC5B, DNAJC5G, DNAJC6, DNAJC22, and DNAJC30 seem to positively regulate virus replication, whereas DNAJB3, DNAJB6, DNAJB8, and DNAJC5 negatively regulate virus replication. Further investigation on the infectivity of the progeny virion demonstrated that only DNAJB8 negatively regulates the progeny virion infectivity. It was further identified that DNAJB8 protein is involved in the downregulation of Vif protein, required for the infectivity of HIV-1 virions. DNAJB8 seems to direct Vif protein for autophagic-lysosomal degradation, leading to rescue of the cellular restriction factor APOBEC3G from Vif-mediated proteasomal degradation, resulting in enhanced packaging of APOBEC3G in budding virions and release of less infective progeny virion particles. Finally, our results also indicate that during the early stage of HIV-1 infection, enhanced expression of DNAJB8 promotes the production of less infective progeny virions, but at the later stage or at the peak of infection, reduced expression of DNJAB8 protein allows the HIV-1 to replicate and produce more infective progeny virion particles. |
36,723,948 | New HIV Vaccine Approach Safely Stimulated Rare Precursors to Broadly Neutralizing Antibodies. | This Medical News article discusses a clinical trial for an HIV vaccine that uses germline targeting, a novel technique to induce rare immune cell precursors of broadly neutralizing antibodies. |
36,723,888 | 68Ga-FAPI PETCT Imaging of Intracranial Syphilitic Gumma Comparison to 18F-FDG PETCT. | Intracranial syphilitic gumma is a rare neurological disease. We present 68Ga-DOTA-FAPI-04 and 18F-FDG PETCT findings of intracranial syphilitic gumma in a 46-year-old man with HIV. In this case, 68Ga-DOTA-FAPI-04 PETCT outperforms 18F-FDG in helping to visualizing syphilitic gumma. Syphilitic gumma can also cause increase FAPI activity. Our findings suggest the potential value of 68Ga-DOTA-FAPI-04 in the diagnosis of syphilis. |
36,723,859 | HIV treatment, antiretroviral adherence and AIDS mortality in people who inject drugs a scoping review. | People who inject drugs (PWID) are a key population for the prevention and care of HIV infection. This scoping review covers recent (post-2010) systematic reviews on engagement of PWID in sequential stages of HIV care from uptake, to achieving viral suppression, and to avoiding AIDS-related mortality. We found that data on engagement of PWID into antiretroviral therapy (ART) were particularly scarce, but generally indicated very low engagement in ART. Studies of adherence and achieving viral suppression showed varying results, with PWID sometimes doing as well as other patient groups. The severity of social, medical and psychiatric disability in this population poses significant treatment challenges and leads to a marked gap in AIDS mortality between PWID and other population groups. Given the multi-level barriers, it will be difficult to reach current targets (UNAIDS fast-track targets of 95-95-95) for ART for PWID in many locations. We suggest giving priority to reducing the likelihood that HIV seropositive PWID will transmit HIV to others and reducing morbidity and mortality from HIV infection and from other comorbidities. |
36,723,770 | Stigma and HIV Treatment Outcomes Among Transgender Women Sex Workers in the Dominican Republic. | Trans women experience multiple forms of intersecting stigma due to trans identity, HIV, and sex work, which can negatively affect their health. There is limited understanding of the relationships between stigma and HIV care and treatment outcomes. We assessed associations between multiple forms and types of stigma and HIV treatment outcomes among trans women who conduct sex work in Santo Domingo, Dominican Republic using cross-sectional survey data. Most participants had received HIV care (91%) and were currently taking anti-retroviral therapy (ART) (84%). Only 64% were virally suppressed. Nearly one-third (32%) had interrupted ART at some point those who had never interrupted ART were more likely to be suppressed. Drug use was associated with ART interruption. Higher enacted HIV stigma was associated with current ART use. Higher enacted HIV stigma and higher anticipated sex work stigma were associated with ART adherence. Higher trans stigma was associated with being virally suppressed. Findings highlight the importance of addressing multiple forms of stigma at the individual and clinic levels to improve and sustain viral suppression. Future research is needed to assess if unexpected associations between stigma and HIV outcomes reflect processes of resilience. Future research is also needed to assess the pathways between drug use, ART interruption, and viral suppression among trans women. |
36,723,769 | Characterization of HIV-Related Stigma in Myanmar. | Characterizing HIV-related stigma and its impacts are important for interventions toward their elimination. A cross-sectional study was conducted in 2016 to evaluate enacted and internalized stigma among adult people living with HIV (PLWH) across four cities in Myanmar using the India Stigma Index questionnaire. Multivariable regression analyses were performed to determine differences in measured enacted and internalized stigma outcomes. Among 1,006 participants, 89% reported any stigma indicator, 47% enacted stigma, and 87% internalized stigma. In regression analysis, city and duration of illness were associated with higher enacted stigma, and younger age was associated with higher internalized stigma. Those with HIV duration > 7.4 years had mean enacted stigma nearly 2 units higher than the overall mean. Internalized stigma increased with duration of illness and leveled off at 5 years. PLWH from smaller cities experienced lower stigma. In Myanmar, nearly 90% of PLWH experience stigma, results that reflect a unique transition point. |
36,723,657 | News in HIV infection, long-acting injectable treatments. | Long-acting injectable therapies have been added to the pharmacological arsenal available for the management of HIV infection, whether in the form of monotherapy (injectable cabotegravir) as part of pre-exposure prophylaxis (PrEP) or dual therapies (injectable cabotegravirrilpivirine) for the treatment of HIV. These treatments are the subject of new international recommendations following the publication of pivotal trials, the results of which will be presented in this review. We will also discuss the practical modalities of their implementation as well as the challenges to be faced in the future. Les traitements injectables à longue durée d’action complètent les options pharmacologiques disponibles dans la prise en charge de l’infection par le VIH, que ce soit sous la forme de monothérapie (cabotégravir injectable) en prophylaxie pré-exposition (PrEP) ou de bithérapie (cabotégravirrilpivirine injectables) en traitement. Ces molécules font l’objet de nouvelles recommandations internationales suite à la publication d’essais déterminants dont les résultats sont détaillés dans cet article. Nous abordons également les modalités pratiques de leur implémentation ainsi que les défis auxquels nous devons nous préparer. |
36,723,512 | Predictors of intact HIV DNA levels among children in Kenya. | We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV. HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at <1 year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log10copiesmillion). Among 65 children, median age at ART initiation was 5 months and median follow-up was 5.2 years 86% of children had CMV viremia pre-ART. Lower pre-ART CD4 percent (adjusted relative risk aRR 0.87, 95% confidence intervals 95%CI 0.79-0.97 p 0.009) and higher HIV RNA (aRR 1.21, 95%CI 1.06-1.39 p 0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4 percent (aRR 0.76, 95%CI 0.65-0.89 p<0.001), CMV viral load (aRR 1.16, 95%CI 1.01-1.34 p 0,041), and first line protease inhibitor-based regimens compared to non-nucleoside reverse transcriptase-based regimens (aRR 1.36, 95%CI 1.04-1.77 p 0,025) predicted higher levels of intact HIV DNA. Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir. |
36,723,511 | Sleep disturbances and their correlation with cardiovascular risk, obesity, and mood disorders in people living with HIV. | The relationship between sleep disorders (SDs), cardiovascular risk (CVR), and mood disorders (MDs) has been studied in detail in the general population, but far less in people living with HIV (PLWH). Cross-sectional analysis in single center cohort of PLWH. Sleep quality was assessed using by Epworth sleepiness scale (ESS), Insomnia Severity Index (ISI), Berlin Questionnaire (BQ), Pittsburgh sleep quality index (PSQI) anxiety and depression were evaluated by the GAD-7 and PHQ-9. Demographic, clinical and HIV-related data were collected, and Framingham and DAD-10 scores were computed in modelling associations with each SDs scale. Data were collected for 721 PLWH on stable combination antiretroviral therapy (cART) (median age of 53 years, 71.8% males, 96% with undetectable HIV RNA, 50.3% on cART potentially affecting sleep, and 20.4% on hypno-inducing drugs), 76.9% had SDs60.3%, 31.3%, 31.1% and 7.9% at PSQI, BQ, ISI, and ESS, respectively. Anxiety and depression were detected in 28.3% and 16.1% participants, respectively. BQ score was independently associated with high BMI (p < 0.001), Framingham risk>10% (p < 0.001), and both DAD-10R and -10F score>10% (p < 0.001 and p 0.031). PSQI and ISI scores were independently associated with depression and anxiety (p < 0.001). No association between SDs and specific antiretroviral regimens, nor HIV-related parameters was detected. In our cohort of PLWH on stable ART, despite the alarmingly higher prevalence, SDs were associated with the same determinants (cardiovascular risk factors and MDs) observed in the general population. |
36,723,509 | Longitudinal patterns of initiation, persistence, and cycling on PrEP among female sex workers and adolescent girls and young women in South Africa, 2016-2021. | Female sex workers (FSW) and adolescent girls and young women (AGYW) face a disproportionately high risk of HIV in South Africa. Oral PrEP can avert new infections, but its effectiveness is linked to consistent use. Early discontinuation of PrEP in this population is high, but less is known about longitudinal patterns of PrEP use, including patterns of re-initiation and cycling. Longitudinal descriptive analysis of routine program data. Between 2016-2021, 40,681 FSW and AGYW initiated PrEP at TB HIV Care, the largest PrEP provider to this population in South Africa and were included. Using survival analyses and group-based trajectory modeling, we described patterns of initiation, discontinuation, re-initiation, and cycling. Total initiations increased over the life of the program for both FSW and AGYW. About 40% of FSW (0.41, 95%CI 0.40-0.42) and AGYW (0.38, 95%CI 0.37-0.38) remained on PrEP at 1-month. FSW were more likely to restart PrEP, however less than 10% restarted PrEP within a year of initiation. Three latent trajectory groups of PrEP use were identified for FSW (low use, early cycling, and ongoing cycling) and two for AGYW (low use and ongoing cycling). Persistence was negatively associated with initiation among AGYW, but there was no clear relationship among FSW. Those initiating later in the program and older women had a reduced risk of discontinuation. Persistence on PrEP was low, but cycling on and off PrEP was common, with early missed visits and inconsistent, but ongoing use. A push to increase PrEP initiations needs to factor in readiness and persistence support, to achieve public health impact. |
36,723,505 | Impact of sub-optimal HIV viral control on activated T-cells an earnest sub study. | HIV viral load (VL) monitoring is generally conducted 6-12 monthly in low- and middle-income countries, risking relatively prolonged periods of poor viral control. We explored the effects of different levels of loss of viral control on immune reconstitution and activation. 208 participants starting Protease Inhibitor (PI)-based second-line therapy in the EARNEST trial (ISRCTN37737787) in Uganda and Zimbabwe were enrolled and CD38HLA-DR immunophenotyping performed (CD8-FITCCD38-PECD3-PerCPHLA-DR-APC centrally gated) in real-time at 0, 12, 48, 96 and 144 weeks from randomisation. Viral Load (Viral load (VL) was assayed retrospectively on samples collected every 12-16 weeks and classified as (1) continuous suppression (<40 copiesml throughout) (2) suppression with transient blips (3) low-level rebound (two or more consecutive VL >40, <5000 copiesml) (4) high-level reboundnon-response (two or more consecutive VL >5000 copiesml). Immunophenotype reconstitution varied between that defined by numbers of cells and that defined by cell percentages. Furthermore, VL dynamics were associated with substantial differences in expression of CD4 and CD8 cell activation markers, with only individuals with high-level reboundnon-response (>5000 copiesml) experiencing significantly greater activation and impaired reconstitution. There was little difference between participants who suppressed consistently and who exhibited transient blips or even low-level rebound by 144 weeks (p > 0.2 vs suppressed consistently). Detectable viral load below the threshold at which WHO guidelines recommend that treatment can be maintained without switching (1000 copiesml) appear to have at most, small effects on reconstitution and activation, for patients taking a PI-based second-line regimen. |
36,723,502 | The impact of COVID-19 pandemic on the dynamic HIV care engagement among people with HIV real-world evidence. | Existing studies examining the impact of the pandemic on engagement in HIV care often capture cross-sectional status, while lacking longitudinal evaluations. This study examined the impact of the pandemic on the longitudinal dynamic change of retention in care and viral suppression status. The electronic health record (EHR) data of this population-level cohort study were retrieved from the statewide electronic HIVAIDS reporting system in South Carolina (SC). The study population was people with HIV (PWH) who had at least one years symmetric follow up observation record before and after the pandemic. Multivariable generalized linear mixed regression models were employed to analyze the impact of the pandemic on these outcomes, adjusting for socio-demographic characteristics and preexisting comorbidities. In the adjusted models, PWH had a lower likelihood of retention in care (adjusted odds ratio aOR 0.806, 95%CI 0.769, 0.844) and a higher probability of virological failure (aOR 1.240, 95%CI 1.169, 1.316) during the peri-pandemic period than pre-pandemic period. Results from interaction effect analysis from each cohort revealed that the negative effect of the pandemic on retention in care was more severe among PWH with high comorbidity burden than those without any comorbidity meanwhile, a more striking virological failure was observed among PWH who reside in urban areas than in rural areas. The COVID-19 pandemic has a negative impact on retention in care and viral suppression among PWH in South Carolina, particularly for individuals with comorbidities and residing in urban areas. |
36,723,491 | Brain volumetrics differ by fiebig stage in acute HIV infection. | People with chronic HIV exhibit lower regional brain volumes compared to people without HIV (PWOH). Whether imaging alterations observed in chronic infection occur in acute HIV infection (AHI) remains unknown. Cross-sectional study of Thai participants with AHI. 112 Thai males with AHI (age 20-46) and 18 male Thai PWOH (age 18-40) were included. Individuals with AHI were stratified into early (Fiebig I-II n 32) and late (Fiebig III-V n 80) stages of acute infection using validated assays. T1-weighted scans were acquired using a 3T MRI performed within five days of antiretroviral therapy (ART) initiation. Volumes for the amygdala, caudate nucleus, hippocampus, nucleus accumbens, pallidum, putamen, and thalamus were compared across groups. Participants in late Fiebig stages exhibited larger volumes in the nucleus accumbens (8% larger p .049) and putamen (19% p < .001) when compared to participants in the early Fiebig. Compared to PWOH, participants in late Fiebig exhibited larger volumes of the amygdala (9% larger p .002), caudate nucleus (11% p .005), nucleus accumbens (15% p .004), pallidum (19% p .001), and putamen (31% p < .001). Brain volumes in the nucleus accumbens, pallidum, and putamen correlated modestly with stimulant use over the past four months among late Fiebig individuals (ps < .05). Findings indicate that brain volume alterations occur in acute infection, with the most prominent differences evident in the later stages of AHI. Additional studies are needed to evaluate mechanisms for possible brain disruption following ART, including viral factors and markers of neuroinflammation. |
36,723,489 | Safety and efficacy of long-acting injectable cabotegravir as pre-exposure prophylaxis to prevent HIV acquisition a systematic review and meta-analysis. | HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines. Systematic review and meta-analysis. We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resista, pregnancy-related adverse events, and sexual behaviour. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively. We identified 12 articlesabstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval 0.07-0.61), resulting in an 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior. CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials. |
36,723,488 | Development of frail RISC-HIV a risk score for predicting frailty risk in the short-term for care of people with HIV. | Frailty is common among people with HIV (PWH), so we developed Frail RISC-HIV, a frailty prediction risk score for HIV clinical decision-making. We followed PWH for up to 2 years to identify short-term predictors of becoming frail. We predicted frailty risk among PWH at 7 HIV clinics across the US. A modified self-reported Fried Phenotype captured frailty, including fatigue, weight loss, inactivity, and poor mobility. PWH without frailty were separated into training and validation sets and followed until becoming frail or 2 years. Bayesian Model Averaging (BMA) and 5-fold-cross-validation Lasso regression selected predictors of frailty. Predictors were selected by BMA if they had >45% probability of being in the best model and by Lasso if they minimized mean squared error. We included age, sex, and variables selected by both BMA and Lasso in Frail RISC-HIV by associating incident frailty with each selected variable in Cox models. Frail RISC-HIV performance was assessed in the validation set by Harrells C and lift plots. Among 3,170 PWH (training set), 7% developed frailty, while among 1,510 PWH (validation set), 12% developed frailty. BMA and Lasso selected baseline frailty score, prescribed antidepressants, prescribed ART, depressive symptomology, and current marijuana and illicit opioid use. Discrimination was acceptable in the validation set, with Harrells C of 0.76 (95%CI 0.73-0.79) and sensitivity of 80% and specificity of 61% at a 5% frailty risk cutoff. Frail RISC-HIV is a simple, easily implemented tool to assist in classifying PWH at risk for frailty in clinics. |
36,723,323 | THE VALUE OF SERUM SEROMUCOID IN THE DIFFERENTIAL DIAGNOSIS OF BACTERIAL PNEUMONIA AND TUBERCULOSIS IN HIV-POSITIVE PATIENTS. | The aim To optimize the differential diagnosis of bacterial pneumonia and tuberculosis in HIV-positive patients based on the value of serum seromucoid. Materials and methods The study included 77 HIV-positive patients with lung pathology. The 1st group consisted of 44 HIV-infected patients with BP the 2nd group - of 33 patients with HIVTB co-infection. Level of SSM, CD4 T-lymphocytes, HIV-1 RNA viral load was determined. Сlinical, laboratory, microscopic, radiological, microbiological, and statistical methods were used in the research. Results In patients with HIVTB co-infection CD4 T-lymphocyte level was lower, and viral load was higher than in HIV-infected patients with BP. The level of SSM was statistically significantly elevated in patients of both groups compared with the control (p<0,001), but in patients with HIVTB co-infection the values were statistically significantly higher (p<0,001). In patients with BP, the content of SSM≤15,95 TU occurred statistically significantly more often than in patients with TB (χ2 65,5 p <0,001). No statistically significant relationship between SSM content and CD4 T-lymphocyte levels was found. Conclusions The content of SSM in patients with HIVTB co-infection is statistically significantly higher than in the group of HIV-infected patients with BP. Determination of SSM level can be used as a rapid method of differential diagnosis of BP and TB in HIV-positive patients that will allow to optimize the diagnostic algorithm at the early stage of hospitalization and to receive the necessary timely treatment for HIV-infected patients. |
36,723,037 | Magnetically localized and wash-free fluorescence immunoassay (MLFIA) proof of concept and clinical applications. | Immunoassays are used for many applications in various markets, from clinical diagnostics to the food industry, generally relying on gold-standard ELISAs that are sensitive, robust, and cheap but also time-consuming and labour intensive. As an alternative, we propose here the magnetically localized and wash-free fluorescence immunoassay (MLFIA) a no-wash assay to directly measure a biomolecule concentration, without mixing nor washing steps. To do so, a fluorescence no-wash measurement is performed to generate a detectable signal. It consists of a differential measurement between the fluorescence of fluorophores bound to magnetic nanoparticles specifically captured by micro-magnets against the residual background fluorescence of unbound fluorophores. Targeted biomolecules (antibodies or antigens) are locally concentrated on micro-magnet lines, with the number of captured biomolecules quantitatively measured without any washing step. The performance of the MLFIA platform is assessed and its use is demonstrated with several biological models as well as clinical blood samples for HIV, HCV and HBV detection, with benchmarking to standard analyzers of healthcare laboratories. Thus, we demonstrated for the first time the versatility of the innovative MLFIA platform. We highlighted promising performances with the successful quantitative detection of various targets (antigens and antibodies), in different biological samples (serum and plasma), for different clinical tests (HCV, HBV, HIV). |
36,722,888 | Single-tube one-step gel-based RT-RPAPCR for highly sensitive molecular detection of HIV. | We developed a single-tube one-step gel-based reverse transcription-recombinase polymerase amplification (RT-RPA)polymerase chain reaction (PCR) (termed SOG RT-RPAPCR) to detect the human immunodeficiency virus (HIV). To improve the assay sensitivity, the RNA template is pre-amplified by RT-RPA prior to PCR. To simplify the detection process and shorten the assay time, we embedded PCR reagents into agarose gel, constructing it to physically separate the reagents from the RT-RPA reaction solution in a single tube. Due to the thermodynamic properties of agarose, the RT-RPA reaction first occurs independently on top of the PCR gel at a low temperature ( |
36,722,804 | Self-reported Human Papillomavirus Vaccination and Vaccine Effectiveness Among Men Who Have Sex with Men A Quantitative Bias Analysis. | Self-report of human papillomavirus (HPV) vaccination has 80-90% sensitivity and 75-85% specificity. We measured the effect of nondifferential exposure misclassification associated with self-reported vaccination on vaccine effectiveness (VE) estimates. Between 2017-2019, we recruited sexually active gay, bisexual, and other men who have sex with men aged 16-30 years in Canada. VE was derived as 1-prevalence ratio × 100% for prevalent anal HPV infection comparing vaccinated (≥1 dose) to unvaccinated men using a multivariable modified Poisson regression. We conducted a multidimensional and probabilistic quantitative bias analysis to correct VE estimates. Bias-corrected VE estimates were relatively stable across sensitivity values but differed from the uncorrected estimate at lower values of specificity. The median adjusted VE was 27% (2.5-97.5th simulation interval -5-49%) in the uncorrected analysis, increasing to 39% (2.5-97.5th simulation interval 2-65%) in the bias-corrected analysis. A large proportion of participants erroneously reporting HPV vaccination would be required to meaningfully change VE estimates. |