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Abstract Background The use of antiretrovirals has increased the survival of People Living with HIV/AIDS (PLWHA), resulting in an aging population and a rise in the incidence of sarcopenia. The lack of uniformity among the prevalences found in studies may be associated with the use of different diagnostic criteria, highlighting the need for local studies to determine the prevalence of sarcopenia. Methods Cross-sectional study to estimate the prevalence and associated factors of sarcopenia using the revised criteria of the European Working Group on Sarcopenia in Older People (EWGSOP2). This study included PLWHA of both sexes, aged 40 years or older, who were treated at the infectious disease outpatient clinic of a tertiary hospital from 2019 to 2021. Muscle mass was quantified through electrical bioimpedance, using resistance and reactance to calculate appendicular lean mass (ALM) in kg/m². Muscle strength, measured in kg, was assessed using a manual dynamometer, and muscle function was evaluated using the gait speed test (m/s). Numerical variables were analyzed using measures of central tendency and dispersion. The chi-square test was used to assess associations in categorical variables. Odds ratios (OR) and 95% Confidence Intervals (CI) were calculated to evaluate the strength of associations. Results Among the 218 PLWHA, the prevalence of sarcopenia was 8.7% (95% CI: 5.6 to 13.3). The mean age of the study population was 51.8 ± 8.3 years; 53.7% were male, 72.9% were brown/Black, 97.7% reported not using illicit drugs, and 24.8% were classified as obese. Multivariate analysis showed that the time since HIV diagnosis (P = 0.022) and the use of illicit drugs were associated with the diagnosis of sarcopenia. Conclusion The prevalence of sarcopenia using the EWGSOP2 criteria was low. People with a longer duration of HIV infection and those using illicit drugs were more likely to develop sarcopenia. …

Abstract Background HIV-1 has well-established mechanisms to disrupt essential pathways in people with HIV, such as inflammation and metabolism. Moreover, diversity of the amino acid sequences in fundamental HIV-1 proteins including Tat and Vif, have been linked to dysregulating these pathways, and subsequently influencing clinical outcomes in people with HIV. However, the relationship between Tat and Vif amino acid sequence variation and specific immune markers and metabolites of the tryptophan-kynurenine (Trp-Kyn) pathway remains unclear. Therefore, this study aimed to investigate the relationship between Tat/Vif amino acid sequence diversity and Trp-Kyn metabolites (quinolinic acid (QUIN), Trp, kynurenic acid (KA), Kyn and Trp/Kyn ratio), as well as specific immune markers (sCD163, suPAR, IL-6, NGAL and hsCRP) in n = 67 South African cART-naïve people with HIV. Methods Sanger sequencing was used to determine blood-derived Tat/Vif amino acid sequence diversity. To measure Trp-Kyn metabolites, a LC–MS/MS metabolomics platform was employed using a targeted approach. To measure immune markers, Enzyme-linked immunosorbent assays and the Particle-enhanced turbidimetric assay was used. Results After adjusting for covariates, sCD163 (p = 0.042) and KA (p = 0.031) were higher in participants with Tat signatures N24 and R57, respectively, and amino acid variation at position 24 (adj R2 = 0.048, β = -0.416, p = 0.042) and 57 (adj R2 = 0.166, β = 0.535, p = 0.031) of Tat were associated with sCD163 and KA, respectively. Conclusions These preliminary findings suggest that amino acid variation in Tat may have an influence on underlying pathogenic HIV-1 mechanisms and therefore, this line of work merits further investigation. …

Abstract Background Cardiovascular disease is a major cause of morbidity in an aging HIV population. However, risk estimation with the most frequent equations usually classifies HIV patients as having a low or moderate risk. Several studies have described a very high prevalence of subclinical atherosclerosis in a middle-aged, non-HIV population. There is insufficient body of knowledge to understand if this is the case in people living with HIV (PLWH). We aim to calculate the proportion of patients with subclinical atherosclerosis in a single site cohort of HIV-infected subjects. Methods We have analyzed chronically HIV infected adults (≥ 18 years) who were on active follow-up in an HIV unit specialized in the care of cardiovascular health. The most recent clinical visit and vascular ultrasonography were used to assess the objectives of our research. Our primary objective was to describe the proportion of participants with subclinical atherosclerosis (focal protrusion into the lumen > 0.5 mm or > 50% of the surrounding IMT or a diffuse thickness > 1.5 mm) in a single site cohort of PLWH. Carotid and iliofemoral territories were evaluated. As a secondary objective we have run a multivariate analysis to determine which HIV and non-HIV factors might be related with the presence of atherosclerotic plaques. Findings We included a total of 463 participants between November 2017 to October 2019. Subjects were predominantly male (84.2%) with a mean age of 48.8 years (SD 10.7). Hypercholesterolemia (36%) was the most prevalent comorbidity followed by Hypertension (18%) and Hypertriglyceridemia (16%). Mean duration of HIV infection is 12.3 years. Overall, participants had been receiving cART for a median of 9.5 years. Subclinical atherosclerosis was found in 197 subjects (42.5%; CI 95% [38.0–47.2]). The disease was found more frequently in the femoral arteries (37.8%) than in the carotid vascular bed (18.6%). Despite some HIV factors correlated with the presence of plaques in a univariate analysis (e.g., time with HIV-1 RNA > 50 copies/mL or time from HIV diagnosis), the only two explanatory factors that remained associated with the presence of atherosclerotic plaques in the multivariate analysis were smoking (OR 5.47, 95% CI 3.36 – 8.90) and age (OR 1.13, 95%CI 1.10 – 1.16). Interpretation We have found a very high prevalence of subclinical atherosclerosis among our cohort of PLWH. Despite having analyzed several HIV factors, age and smoking have been found to be the only factors associated with the development of atherosclerotic plaques. …

Objective: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA). Design: Site-level survey conducted in 2020–2021 among HIV clinics in low- and middle-income countries (LMICs). Methods: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for patients on ART switching to dolutegravir-based regimens. We used generalized estimating equations to assess associations between clinic rollout of both first- and second-line dolutegravir-based ART regimens (dual rollout) and site-level factors. Results: Of 179 surveyed clinics, 175 (98%) participated; 137 (78%) from Africa, 30 (17%) from the Asia-Pacific, and 8 (5%) from Latin America. Most clinics (80%) were in low- or lower-middle-income countries, and there were a mix of primary-, secondary- and tertiary-level clinics. Ninety percent reported rollout of first-line dolutegravir, 59% of second-line, 94% of first- or second-line and 55% of dual rollout. The adjusted odds of dual rollout were higher among tertiary-level (aOR 4.00; 95% CI 1.39 to 11.47) and secondary-level clinics (aOR 3.66; 95% CI 2.19 to 6.11) than in primary-level clinics. Over half (59%) of clinics that introduced first- or second-line dolutegravir-based ART required recent viral load testing before switching to dolutegravir, and 15% performed genotypic resistance testing at switch. Conclusions: Dolutegravir-based ART was rolled out at nearly all IeDEA clinics in LMICs, yet many switched patients to dolutegravir without recent viral load testing and drug resistance testing was rarely performed. Without such testing, drug resistance among patient switching to dolutegravir may go undetected. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: Low food security is common among people with HIV (PWH) and is associated with poorer health outcomes. Frailty, an aging-related outcome that is increasingly prevalent among PWH, may be stimulated by low food security. We assessed associations between food security and frailty among PWH. Methods: The Impact of Physical Activity Routines and Dietary Intake on the Longitudinal Symptom Experience of People Living with HIV (PROSPER-HIV) study follows PWH to evaluate how diet and physical activity impact symptoms. We utilized food security and frailty data from PROSPER-HIV Year 1 visits (January 2019 to July 2022) to estimate associations. Food security was measured via the validated two-item Food Security Questionnaire and categorized as Food Secure, Low Food Security, or Very Low Food Security. Frailty was measured with the Fried frailty phenotype, and categorized as robust, prefrail, and frail. We used relative risk regression to estimate associations between food security and frailty status, adjusted for demographic characteristics. Results: Among 574 PWH, nearly one-quarter were women (22%), mean age was 52 years old, 8% were frail, and 46% prefrail. Low food security was reported among nearly one-third of PWH: 13% Low Food Security and 18% Very Low Food Security. Compared with being Food Secure, we found Low Food Security was associated with frailty [prevalence ratio: 4.06 (95% confidence interval (CI) 2.16–7.62] and Very Low Food Security was associated with both prefrailty [1.48 (1.23–1.78)] and frailty [5.61 (3.14–10.0)], as compared with robust status. Conclusion: Low food security was associated with increased frailty among PWH in this study, suggesting a potential intervention point to promote healthy aging. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Background: Men who inject drugs who have sex with men (MWIDSM) may acquire HIV through injecting drugs or sex. Interventions to increase awareness of HIV preexposure prophylaxis (PrEP) have focused on gay/bisexual MSM and may not be reaching heterosexual-identifying men or people who inject drugs (PWID). We explored changes in PrEP awareness and use among MWIDSM from 2018 to 2022 by sexual identity. Methods: We used data from the 2018 and 2022 National HIV Behavioral Surveillance among PWID recruited via respondent-driven sampling in 19 urban areas in the US. We examined changes in PrEP awareness and use over time by sexual identity among HIV-negative men who inject drugs and who had sex with another man in the past 12 months using log-linked Poisson regression models with robust standard errors with an interaction term between year and sexual identity. Results: Among 758 HIV-negative MWIDSM (463 in 2018; 295 in 2022), nearly all sample participants were likely indicated for PrEP (94.2 and 92.9%, respectively). PrEP awareness increased from 2018 to 2022 among gay/bisexual-identifying MWIDSM [45.5–65.5%; aPR = 1.49, 95% confidence interval (95% CI) = 1.30–1.70] but remained stable for heterosexual-identifying MWIDSM (39.4–40.8%; aPR = 1.01, 95% CI 0.75–1.36). PrEP use remained low among all MWIDSM (2.5–7.7%, among heterosexually identifying; 15.3 to 10.2% among gay/bisexual-identifying). Conclusion: PrEP awareness increased among gay/bisexual-identifying MWIDSM but not among heterosexual-identifying. PrEP use was low for all MWIDSM. Public health initiatives catered to MWIDSM should focus on improved campaigns and expanding PrEP accessibility in existing healthcare, harm reduction, and social services. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

No abstract available…

Objective: To compare the model-predicted benefits, harms, and cost-effectiveness of cytology, cotesting, and primary HPV screening in U.S. women living with HIV (WLWH). Design: We adapted a previously published Markov decision model to simulate a cohort of U.S. WLWH. Setting: United States. Subjects, participants: A hypothetical inception cohort of WLWH. Intervention: We simulated five screening strategies all assumed the same strategy of cytology with HPV triage for ASCUS for women aged 21 to 29 years. The different strategies noted are for women aged 30 and older as the following: continue cytology with HPV triage, cotesting with repeat cotesting triage, cotesting with HPV16/18 genotyping triage, primary hrHPV testing with cytology triage, and primary hrHPV testing with HPV16/18 genotyping triage. Main outcome measure(s): The outcomes include colposcopies, false-positive results, treatments, cancers, cancer deaths, life-years and costs, and lifetime quality-adjusted life-years. Results: Compared with no screening, screening was cost-saving, and > 96% of cervical cancers and deaths could be prevented. Cytology with HPV triage dominated primary HPV screening and cotesting. At willingness-to-pay thresholds under $250,000, probabilistic sensitivity analyses indicated that primary HPV testing was more cost-effective than cotesting in over 98% of the iterations. Conclusions: Our study suggests the current cytology-based screening recommendation is cost-effective, but that primary HPV screening could be a cost-effective alternative to cotesting. To improve the cost-effectiveness of HPV-based screening, increased acceptance of the HPV test among targeted women is needed, as are alternative follow-up recommendations to limit the harms of high false-positive testing. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Objective: The aim of this study was to characterize T cell activation, exhaustion, maturation and Treg frequencies in individuals who acquire perinatal HIV (PHIV), in individuals who acquired HIV as adult (AHIV), and in healthy controls (HC). Design: This cross-sectional study included people with HIV ≥ 14 and…

Objective: To examine the effects of internalized HIV stigma on viral non-suppression via depressive symptoms, alcohol use, illicit drug use, and medication adherence and investigate whether social support moderates these effects. Design: Longitudinal observational clinical cohort of patients in HIV care in the US. Methods: Data from the CFAR Network for Integrated Clinical Systems (2016–2019) were used to conduct structural equation models (SEM) to test the indirect effects of internalized HIV stigma on viral non-suppression through depressive symptoms, illicit drug use, alcohol use, and medication adherence. Moderated mediation with an interaction between social support and internalized HIV stigma was examined. Results: Among 9,574 individuals included in the study sample, 81.1% were male and 41.4% were Black, non-Hispanic. The model demonstrated good fit (root mean square error of approximation = 0.028; standardized root means square residual = 0.067). The overall indirect effect was significant (b = 0.058; se  = 0.020; β = 0.048; 95%CI = .019-.098), indicating that internalized HIV stigma\'s impact on viral non-suppression was mediated by depressive symptoms, illicit drug use, and medication adherence. An interaction was observed between internalized HIV stigma and social support on alcohol use, however, there was no moderated mediation for any of the mediators. Conclusions: Internalized HIV stigma indirectly impacts viral non-suppression through its effects on depressive symptoms, illicit drug use, and medication adherence. Social support may buffer the impact, but more research is needed. Understanding the pathways through which internalized stigma impacts viral suppression is key to improving health of people with HIV. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

Objective(s): Children with HIV may experience adverse neurocognitive outcomes despite antiretroviral therapy (ART). Cytomegalovirus (CMV) is common in children with HIV. Among children on ART, we examined the influences of early HIV viral load (VL) and CMV DNA on neurocognition. Design: We determined the association between pre-ART VL, cumulative VL, and CMV viremia and neurocognition using data from a cohort study. Methods: Children who initiated ART before 12 months of age were enrolled from 2007-2010 in Nairobi, Kenya. Blood was collected at enrollment and every 6 months thereafter. Four neurocognitive assessments with 12 domains were conducted when children were a median age of 7 years. Primary outcomes included cognitive ability, executive function, attention, and motor. Generalized linear models were used to determine associations between HIV VL (pre-ART and cumulative; N = 38) and peak CMV DNA (by 24 months of age; N = 20) and neurocognitive outcomes. Results: In adjusted models, higher peak CMV viremia by 24 months of age was associated with lower cognitive ability and motor z-scores. Higher pre-ART HIV VL was associated with lower executive function z-scores. Among secondary outcomes, higher pre-ART VL was associated with lower mean nonverbal and metacognition z-scores. Conclusion: Higher pre-ART VL and CMV DNA in infancy were associated with lower executive function, nonverbal and metacognition scores and cognitive ability scores in childhood, respectively. These findings suggest long-term benefits of early HIV viral suppression and CMV control on neurocognition. Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.

by Brian D. Williamson, Liana Wu, Yunda Huang, Aaron Hudson, Peter B. Gilbert Combination monoclonal broadly neutralizing antibodies (bnAbs) are currently being developed for preventing HIV-1 acquisition. Recent work has focused on predicting in vitro neutralization potency of both individual bnAbs and combination regimens against HIV-1 pseudoviruses using Env sequence features. To predict in vitro combination regimen neutralization potency against a given HIV-1 pseudovirus, previous approaches have applied mathematical models to combine individual-bnAb neutralization and have predicted this combined neutralization value; we call this the combine-then-predict (CP) approach. However, prediction performance for some individual bnAbs has exceeded that for the combination, leading to another possibility: combining the individual-bnAb predicted values and using these to predict combination regimen neutralization; we call this the predict-then-combine (PC) approach. We explore both approaches in both simulated data and data from the Los Alamos National Laboratory’s Compile, Neutralize, and Tally NAb Panels repository. The CP approach is superior to the PC approach when the neutralization outcome of interest is binary (e.g., neutralization susceptibility, defined as inhibitory 80% concentration < 1 μg/mL). For continuous outcomes, the CP approach performs nearly as well as the PC approach when the individual-bnAb prediction algorithms have strong performance, and is superior to the PC approach when the individual-bnAb prediction algorithms have poor performance. This knowledge may be used when building prediction models for novel antibody combinations in the absence of in vitro neutralization data for the antibody combination; this, in turn, will aid in the evaluation and down-selection of these antibody combinations into prevention efficacy trials.

by Xingguang Li, Nídia S. Trovão HIV-1 CRF08_BC is a significant subtype in China, though its origin and spread remain incompletely understood. Previous studies using partial genomic data have provided insights but lack comprehensive analysis. Here, we investigate the early evolutionary and spatiotemporal dynamics of HIV-1 CRF08_BC in China and Myanmar using near-complete genome sequences. We analyzed 28 near-complete HIV-1 CRF08_BC genomes from China and Myanmar (1997–2013). Phylogenetic, molecular clock, and Bayesian discrete trait analyses were performed to infer the virus’s origin, spread, and associated risk groups. Based on Bayesian time-scaled inference with the best-fitting combination of models determined by marginal likelihood estimation (MLE), we inferred the time to the most recent common ancestor (TMRCA) and evolutionary rate of HIV-1 CRF08_BC to be at 3 October 1991 (95% HPD: 22 February1989–27 November 1993) and 2.30 × 10−3 substitutions per site per year (95% HPD: 1.96 × 10−3–2.63 × 10−3), respectively. Our analysis suggests that HIV-1 CRF08_BC originated in Yunnan Province, China, among injecting drug users, and subsequently spread to other regions. This study provides valuable insights into the early dynamics of HIV-1 CRF08_BC through combined genomic and epidemiological data, which may inform effective prevention and mitigation efforts. However, the limited genomic data influenced the extent of our findings, and challenges in collecting accurate risk group information during surveillance were evident.

Background: Human immunodeficiency virus type 1 (HIV-1) elite controllers (ECs) are a rare subset of people living with HIV-1 (PLWH) who control viral replication in the absence of antiretroviral therapy (ART) and may provide a model for a functional cure. We investigated the role of natural killer (NK) cells in HIV-1 ECs from South Africa. Methods: Phenotypic (CD69, CD38, CD57, PD-1), functional (CD107a, IFN-γ), and nutrient transporter profiles (glucose transporter 1, CD98) of NK cells from ECs (n=20), viraemic progressors (VPs; n=19), people living with HIV-1 (PLWH) on ART (n=20), and people without HIV-1 (PWOH; n=21) were analysed using flow cytometry. The Kruskal-Wallis test followed by the Mann-Whitney U test were used to determine differences among the study groups. The Spearman’s rank correlation coefficient was used to determine significant associations. Results: Compared to the other study groups, the percentage of CD69-expressing NK cells was higher in ECs, whereas the percentage of CD38-expressing NK cells was higher in VPs. Percentages of CD69+CD38- NK cells were elevated in ECs compared to VPs (p = 0.003), but were not different to PLWH on ART and PWOH. Differentiation, exhaustion, and metabolic profiles were not different in ECs compared with PLWH on ART and PWOH, however, NK cell function was lower than in PWOH. Conclusion: These findings demonstrate that NK cells from ECs have an activated, mature profile with low levels of immune exhaustion and a reduced metabolic phenotype suggesting functional competence. This insight could inform the development of novel immunotherapeutic strategies for treating HIV-1. Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Journal of Medical Virology, Volume 96, Issue 9, September 2024.

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 111 Issue: 3 Pages: 462-471 …

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 111 Issue: 3 Pages: 589-597 …

by Moses Mukosha, Abigail Hatcher, Mwansa Ketty Lubeya, Innocent Maposa, Benjamin H. Chi, Wilbroad Mutale Background Persistent hypertension is common after preeclampsia and is causally tied to later cardiovascular risks. This study examined whether being HIV-infected and on antiretroviral therapy (ART) is associated with persistent postpartum hypertension among women diagnosed with preeclampsia. Methods We conducted a six-month prospective cohort study at Kanyama and Women and Newborn hospitals from January 01, 2022, to June 30, 2023, among 190 women diagnosed with preeclampsia (59 HIV-positive, 131 HIV-negative). Sociodemographic and clinical characteristics were collected at delivery, six weeks, three months and six months after giving birth. Persistent hypertension was diagnosed if a participant presented with elevated blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg and/or taking medication for hypertension at the study visit. We used a generalized estimating equation to describe the relationship between treated HIV and persistent hypertension six months following delivery. Results We retained 136 participants (71.6%) to six months postpartum, at a median age of 30 years. Overall, persistent hypertension at six weeks, three months, and six months postpartum was common (37.4%, 17.1% and 16.9%, respectively). Six-week postpartum prevalence was higher in the HIV group than HIV-negative group (54.6% vs 28.8%, p…

Proceedings of the National Academy of Sciences, Volume 121, Issue 36, September 2024.