BACKGROUND:People with HIV (PWH) develop chronic obstructive pulmonary disease (COPD) more frequently and at younger ages than the general population, yet the circulating proteomic correlates of COPD in PWH remain poorly characterized. METHODS:We applied a targeted 92-plex organ damage proteomics panel (Olink Organ Damage) to compare serum protein profiles between 38 PWH with established COPD and 49 PWH without COPD, enrolled in a prospective observational cohort. RESULTS:Differential abundance analysis adjusted for age, sex, BMI, and current smoking status identified several proteins (NUCB2, ALDH3A1, CLEC1A, CALCA, BAMBI, PGF) significantly elevated in PWH with COPD after correction for multiple testing, with several additional proteins reaching nominal significance only. Using a repeated nested cross-validated LASSO framework, a proteomic model achieved modest discriminatory performance (area under the curve, AUC 0.67), comparable to a routine laboratory model (AUC 0.74). A clinical model incorporating FEV1 achieved higher discrimination (AUC 0.84), though this comparison is limited by the partial construct overlap with the GOLD-based COPD definition. Notably, the proteomic model showed statistically significant incremental discriminative value over a spirometry-free clinical model (age, sex, BMI, smoking status; AUC 0.47), suggesting the proteomic signature captures COPD-relevant biological information beyond demographics and smoking history. A stacked meta-model combining all modalities did not significantly outperform the FEV1-inclusive clinical model (AUC 0.87). CONCLUSIONS:Our findings provide exploratory evidence for candidate circulating organ damage markers of COPD in PWH and provide a basis for further studies into the mechanisms and immunopathology of this comorbidity, including studies in larger cohorts with HIV-negative comparator groups.
OBJECTIVE:The objective of the study was to establish whether HIV-1 sub-subtype A6 (HIV-1A6) is a risk factor for virological failure in people with HIV (PWH) treated with the high genetic barrier integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) or bictegravir (BIC). METHODS:The virological outcome of first-line DTG or BIC-containing antiretroviral therapy (ART) was assessed in 261 people with HIV-1A6 (PWH-1A6) and 1042 people with HIV-1B (PWH-1B) starting treatment between January 2014 and May 2025 with follow-up for at least one year in the EuResist Integrated Database. RESULTS:Most PWH-1A6 were recent migrants from Ukraine. The event rates per 100 person-years follow-up were higher in PWH-1A6 for low-level viremia (LLV, 2.71 vs. 1.71, P = 0.049) and virological failure with more than 1000 HIV RNA copies/mL (4.12 vs. 2.03, P < 0.001) than in PWH-1B. At the end of follow-up, 226/261 (86.6%) PWH-1A6 and 936/1042 (89.8%) PWH-1B had viral load below 50 copies/ml (P = 0.132). INSTI DRMs were observed in 5/219 (2.3%) available integrase sequences of PWH-1A6, including two cases detected at virological failure with more than 1000 HIV RNA copies/ml and two cases in virologically suppressed PWH-1A6. In total, 12/261 PWH-1A6 discontinued DTG- or BIC-containing ART, including three individuals who were not virologically suppressed at discontinuation. CONCLUSION:In PWH treated with DTG or BIC-containing first-line ART, LLV and virological failure with more than 1000 HIV RNA copies/ml were observed more frequently in PWH-1A6 than in PWH-1B. However, such events rarely resulted in INSTI resistance or discontinuation of INSTI-containing ART.
BACKGROUND:People with HIV (PWH) remain at risk for cognitive impairment, despite effective antiretroviral therapy (ART), a phenomenon linked to chronic immune activation and inflammation. Cytomegalovirus (CMV) has been implicated in HIV-associated neurocognitive impairment, but most studies rely on serologic measures that may not capture biologically relevant viral-host interactions. Few studies have examined cell-associated CMV markers or evaluated sex-specific associations with cognition. METHODS:We conducted a retrospective cross-sectional analysis of 485 PWH on suppressive ART (HIV RNA<200 copies/ml). Cognitive performance was assessed globally and across seven domains. Cell-associated CMV, Epstein-Barr virus (EBV), and HIV cell-associated DNA in peripheral blood mononuclear cells (PBMCs) were quantified by ddPCR, and CMV and EBV immunoglobulin G (IgG) levels were measured by ELISA. Multivariable linear regression models adjusted for demographic and clinical covariates were used to assess associations with cognitive performance, including evaluation of sex interactions, with false discovery rate correction applied. RESULTS:In adjusted models, lower cell-associated CMV DNA, but not CMV IgG, EBV markers, or HIV DNA, was associated with poorer working memory and global cognitive performance. Significant interactions between CMV DNA and sex were observed for global, executive function, processing speed, and memory. In sex-stratified analyses, these associations were present among women but not in men. CONCLUSIONS:Cell-associated CMV DNA demonstrates sex-modified associations with cognitive performance among ART-suppressed PWH, with effects observed primarily in women. These findings, based on cellular rather than serologic CMV measures, underscore the complexity of host-virus interactions and cautions against interpreting cell-associated CMV DNA as a simple proxy for pathogenic viral activity.
OBJECTIVE:Risk of acute/recent hepatitis C virus infection (ARHCV) and bacterial sexually transmitted infections (STIs) among MSM (MSM-HIV) is heterogeneous. We aimed to identify clinical phenotypes and assess their association with incident ARHCV and bacterial STIs. DESIGN:A prospective multicenter cohort study. METHODS:Between 2022 and 2024, MSM-HIV were recruited from 10 centers in Madrid and followed for 12 months with HCV and bacterial STI screening. App-based questionnaires captured behavioral and mental health data. Thirty-eight variables were analyzed using principal component analysis and hierarchical clustering to derive clinical phenotypes. RESULTS:A total of 529 participants were included (median age 41 years). Three phenotypes were identified: CP1 (n = 328, 62.0%), CP2 (n = 133, 25.1%), and CP3 (n = 68, 12.9%), representing different levels of sexual risk, substance use, and prior STI/HCV history. ARHCV incidence was 0.94, 0.72, and 11.76 per 100 person-years in CP1, CP2, and CP3, respectively, and was higher in CP3 than in CP1 (incidence rate ratio [IRR] 12.49, 95% confidence interval [CI] 3.00-73.08) and CP2 (16.25, 2.18-720.93). Bacterial STI incidence was 33.29, 60.83, and 61.76 per 100 person-years, respectively, and was higher in CP2 (IRR 1.83, 95% CI 1.36-2.46) and CP3 (IRR 1.86, 95% CI 1.27-2.68) than in CP1. CONCLUSION:Clinical phenotypes stratified ARHCV and bacterial STI incidence among MSM-HIV. ARHCV was concentrated in a small high-exposure subgroup, whereas bacterial STIs were more frequent in intermediate and high-exposure phenotypes. Phenotype-based approaches may help guide risk stratification and prevention in HIV care.
OBJECTIVES:This study explored how participants and decliners perceived the French ANRS-175-RHIVIERA-01 trial, which evaluated HIV control during analytical treatment interruption (ATI) among individuals treated with antiretroviral treatment (ART) since acute HIV infection, virologically suppressed, and carrying the HLA-B35/53Bw4TTC2 genotype. It also explored how participants' experiences evolved over follow-up. METHODS:Between 2023 and 2024, semi-structured interviews were conducted with decliners and participants. Interviews were analyzed using interpretative description and thematic analysis. RESULTS:We interviewed 13 participants (3 women) and 3 decliners (all men). Median age was 51, and median time since diagnosis was 10 years. Participants described the trial as 'good news', hoped for personal benefit, and expressed a sense of moral obligation toward healthcare providers (HCPs). Decliners perceived no personal benefit and considered ATI too risky. Most participants experienced ART interruption positively, although only women described it as a 'relief'. Most appreciated the home-based blood sampling option. Experiences evolved during viral rebound, shaped by HCPs' discourses, viral load levels, and symptoms. Those who resumed ART experienced it as a disappointment, and sometimes as a 'failure'. Participants mobilized three forms of experiential knowledge: physical, clinical, and theoretical. All were satisfied with their decision to participate. CONCLUSION:Our findings show that ATI is not a homogeneous experience but a dynamic process comprising three successive phases: ART interruption, viral rebound, and, for some, ART resumption. Moreover, they highlight the need for careful semantic framing in interactions with eligible individuals, exploration of HCPs' emotional investment, and integration of gender-related considerations in future research.
OBJECTIVE:To compare neurodevelopment through 36 months between breastfed children who are HIV-exposed and uninfected (CHEU) exposed to maternal dolutegravir (DTG)-based antiretroviral therapy (ART) and children born to mothers without HIV (CHU). METHODS:We enrolled a prospective cohort of pregnant women with and without HIV in Migori, Kenya, and followed infants to 36 months. Neurodevelopment was assessed at 24 and 36 months using the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4). Outcomes included cognitive, language, and motor z-scores, domain-specific delay (z-score<-1SD), and any delay. Multivariable linear and Poisson regression compared CHEU and CHU, and mixed-effects models evaluated developmental trajectories. RESULTS:Among 293 children (CHEU = 149; CHU = 144), 49% were female and 9% were preterm. Breastfeeding at 12 months was similar between groups. Most CHEU (89%) were DTG-exposed in-utero. At 24 months, 43% had any delay (42% CHEU; 44% CHU), with similar prevalence at 36 months (37% CHEU; 35% CHU). Risk of fine motor delay was significantly higher among CHEU in unadjusted analyses but not after adjustment. Bayley-4 scores and trajectories did not differ between groups. CONCLUSION:Fine motor delay was more common among CHEU, but lack of difference in adjusted analyses suggests these delays were likely attributable to socio-demographic rather than biologic factors. The high prevalence of delays in both groups underscores the strong influence of environmental and nutritional factors on early child development.
OBJECTIVE:Long-acting cabotegravir (CAB-LA) pre-exposure prophylaxis (PrEP) is highly effective. In Phase 2a trials, males had higher CAB pharmacokinetic (PK) trough concentrations than females after the first injection but lower troughs than females after subsequent injections. We report the first analysis of sex differences in CAB PK in a high HIV-burden setting: Kenya and Uganda. METHODS:The SEARCH Dynamic Choice HIV Prevention study provided CAB-LA 600 mg intramuscularly (IM) as an HIV prevention option. Among randomly-sampled participants with injections ≤28 days after target date, plasma CAB trough concentrations were measured, compared by sex, and analyzed in relation to published targets of protein-adjusted concentrations for 90% inhibition of virus (PAIC90). RESULTS:Among 97 participants, at week 4, median CAB troughs were higher among men (2.1 μg/ml, IQR 1.4-2.5) than women (1.5, 1.0-1.8, P = 0.001). Median CAB levels were lower among men than women at weeks 24 (1.1, 0.4-1.7 vs. 1.8, 1.3-2.9, P < 0.001) and 48 (1.1, 0.6-2.1 vs. 1.8, 1.5-2.4, P = 0.02). At least 80% of participants had CAB levels ≥4× PAIC90 at weeks 4-16. At weeks 24 and 48, CAB levels were ≥4× PAIC90 among 92% of women and 68% of men. No participants receiving CAB-LA acquired HIV. CONCLUSIONS:In the first PK study of CAB-LA PrEP in East Africa, CAB concentrations were lower among men than women after the second and later injections. By weeks 24 and 48, fewer men than women had CAB troughs above published PK targets, though no participants acquired HIV. Findings highlight the importance of examining sex differences and real-world forgiveness in PK with long-acting PrEP scale-up.
OBJECTIVES:High viral load and low CD4+ cell count may be associated with increased risk of mpox acquisition. However, prior studies have not evaluated whether longitudinal trends in HIV lab measures, measured as the slope over time, are associated with mpox acquisition or severe mpox. Therefore, we evaluated whether longitudinal trends in CD4+ cell count (cells/μl), viral load (copies/ml), and copy-years viremia (CYV) (copies × years/ml) were associated with increased risk of mpox acquisition. DESIGN:We conducted a nested case-control study among participants in the DC Cohort, a longitudinal study on people with HIV (PWH) in Washington, DC. METHODS:Cases were defined as participants with mpox and were matched to five controls using risk set-sampling. Both two-stage modeling and joint modeling approaches were used to evaluate whether longitudinal trends in CD4+ cell count, viral load, and CYV were associated with mpox acquisition. RESULTS:We evaluated 53 cases of mpox and 248 matched controls, with 13.7% of cases having severe mpox. An increased slope of CYV was associated with an increased risk of mpox acquisition based on the joint modeling approach, after adjusting for AIDS and known antiretroviral regimen [hazard ratio (95% CI): 1.11 (1.04-1.18)]. CONCLUSION:Clinicians should consider a patient's entire history of viral load, not just viral load measured at one point in time, when evaluating risk of mpox.
BACKGROUND:Semaglutide, widely used for diabetes and obesity, has raised concerns about neuropsychiatric risks, including depression and suicidality. Given the high burden of depression among people with HIV (PWH), we assessed whether semaglutide initiation worsens depressive symptoms. METHODS:We conducted a within-person pre-post study of PWH initiating semaglutide at nine Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) sites between April 2018 and October 2024. Depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) collected during routine care before and after semaglutide initiation. We estimated changes in PHQ-9 scores after semaglutide initiation using linear mixed models, overall and stratified by baseline depression severity (0-4 no/minimal, 5-9 mild, 10-14 moderate, and ≥15 moderately-severe to severe), body mass index (BMI), diabetes, and antidepressant use. RESULTS:Among 354 PWH (mean age 54; 77% male; 38% non-Hispanic White; 78% obesity; 60% diabetes), baseline PHQ-9 scores were 0-4 in 53%, 5-9 in 28%, 10-14 in 10%, and ≥15 in 9%. Semaglutide was not associated with overall changes in depressive symptoms (ΔPHQ-9 -0.1 [95% confidence interval (CI) -0.7, 0.5]). Scores increased slightly in those with no/minimal baseline depression (+1.2 [95% CI 0.5, 1.8]), were stable in mild/moderate depression, and decreased in moderately-severe to severe depression (-4.7 [95% CI -7.3, -2.2]). No worsening was observed across BMI, diabetes, or antidepressant subgroups. CONCLUSION:Semaglutide initiation was not associated with worsening depressive symptoms among PWH in care. While individual responses may vary, these findings add to evidence on semaglutide safety regarding mood in a high-risk population.
BACKGROUND:Women with HIV (WWH) are disproportionately affected by cognitive impairment across multiple domains, with learning and memory consistently among the most vulnerable. Mechanistic investigations into the increased burden of cognitive impairment in people with HIV have highlighted mitochondrial dysfunction as a potential contributor. This study examined associations between two peripheral markers of mitochondrial health, mitochondrial DNA copy number (mtDNAcn) and mitochondrial bioenergetic function, and cognitive function in WWH. We hypothesized that mtDNAcn and mitochondrial function metrics would demonstrate distinct associations with cognitive outcomes, particularly learning and memory. METHODS:Fifty-eight WWH completed 12 neuropsychological tests assessing - verbal learning, verbal memory (recall and recognition), attention, working memory, executive function, fluency, processing speed, and motor function. Peripheral blood mononuclear cells (PBMCs) were isolated, and mitochondrial health was assessed using qPCR (mtDNAcn) and the Seahorse Cell Mito Stress Test (mitochondrial function). Pearson correlations examined associations between mitochondrial health and cognitive domain scores. RESULTS:Participants were on average 54.9 years old (SD = 8.2), 94.8% were Black, 58.6% had a lifetime diagnosis of major depressive disorder, and 63.7% met criteria for cognitive impairment in ≥2 domains. Higher mitochondrial proton leak was significantly associated with worse verbal memory including recall ( r = -0.396, P = 0.002) and recognition ( r = -0284, P = 0.031), as well as poorer working memory ( r = -0.261, P = 0.048). No significant associations were observed between mtDNAcn and cognition. CONCLUSIONS:These findings identify peripheral mitochondrial proton leak as a potential biological correlate of verbal and working memory difficulties in WWH and highlight the importance of assessing multiple dimensions of mitochondrial health when investigating cognitive impairment.
OBJECTIVE:To evaluate virological outcomes of people with HIV (PWH) and adherence challenges to oral antiretroviral therapy (ART) who initiate long-acting injectable ART. DESIGN:Observational cohort study. SETTING:Single-center urban HIV primary care clinic at the University of California San Diego. PARTICIPANTS:All PWH who initiated long-acting injectable (LAI)-ART between November 2021 and September 2023 with documented adherence challenges to oral ART. MAIN OUTCOME MEASURES:The primary outcomes were virologic failure (two consecutive viral loads ≥200 copies/ml, one viral load ≥1000 copies/ml, or one viral load ≥200 copies/ml with evidence of resistance mutation to LAI-ART ≥30 days after initiation of LAI-ART) or discontinuation of LAI-ART for any reason within 96 weeks of initiation. RESULTS:Of the 62 eligible individuals, 48 (77.4%) remained virologically suppressed on LAI-ART and 14 (22.6%) discontinued therapy by 96 weeks. Of these 14 individuals, 3 experienced virologic failure (at 28, 40, and 42 weeks) and 3 were lost to follow-up. There were similar outcomes among the 26 participants with active substance use, of whom 18 (69%) remained suppressed on LAI-ART at 96 weeks. The remaining participants discontinued LAI-ART due to preference, adverse events, insurance issues, or death. CONCLUSION:High rates of viral suppression were achieved and maintained at 96 weeks, supporting the use of LAI-ART among those with adherence challenges to oral ART, including those with significant barriers to care, including substance use disorder and psychiatric comorbidities.
BACKGROUND:Smoking remains a major public health issue in people with HIV (PWH). Given the recent uptake of semaglutide for weight management and/or diabetes treatment in PWH and emerging evidence of antiaddictive properties, we studied changes in tobacco cigarette smoking among PWH initiating semaglutide in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort. METHODS:We conducted a prepost within-person study examining changes in tobacco cigarette intensity (cigarettes/day) among PWH who reported currently smoking tobacco cigarettes at the time of semaglutide initiation between 04/2018-11/2025 across 10 CNICS sites. Smoking intensity was collected via the CNICS clinical assessment of patient reported instruments administered during routine clinical visits. We used linear mixed models adjusted for age, sex, race/ethnicity, and time to estimate the average change in smoking intensity level following initiation of semaglutide. RESULTS:There were 123 PWH who reported current smoking at the time of semaglutide initiation, with an average of 10.5 cigarettes/day. The mean age was 51 years, 24% were female, and 95% were virally suppressed (<200 copies/mL). Most (93%) had a standard indication for semaglutide therapy, including 77% of PWH with a body mass index ≥30 kg/m2 and 61% with diabetes at baseline. We found a reduction of -2.5 (95% confidence interval: -3.7 to -1.3) cigarettes smoked per day among PWH after semaglutide initiation. CONCLUSION:New use of the GLP-1 medication semaglutide in PWH who smoked resulted in a mean decrease of 2.5 cigarettes per day representing a 24% drop in total smoking intensity, and 21% reported not smoking at the end of follow-up.
BACKGROUND:Long-acting drugs were recently introduced for HIV treatment, so there are no medium-term or long-term data in real-world settings. Aims were to assess the cumulative probability of treatment discontinuation and the proportion of people with HIV (PWH) with HIV RNA less than 50 copies/ml at month 24 among participants switching to cabotegravir (CAB) and rilpivirine (RPV). METHODS:SCohoLART is a single-center, prospective, cohort study enrolling PWH on virological suppression who switched to bimonthly long-acting CAB/RPV.Treatment discontinuation occurred at switch to another regimen for any reason including virological failure; virological failure was defined as HIV RNA at least 50 copies/ml at two consecutive measurements or a single HIV RNA at least 1000 copies/ml. Participants' characteristics were reported as median (interquartile range, IQR) or frequency (%). Cumulative probabilities of TD were estimated by Kaplan-Meier curve. RESULTS:We evaluated 549 participants: 501 (91.3%) were men and median age was 49 (40-56). At the time of switching, median years from HIV diagnosis and of ART were 13.8 (8.7-20.4) and 11.3 (7.9-17.3).During a median follow-up of 24.0 (17.0-26.8) months, 86 PWH experienced treatment discontinuations (15.6%), including 6 (1.1%) for virological failure, 37 (6.7%) for injection site reactions (ISRs) and 17 (3.1%) for lifestyle changes incompatible with administrations. The cumulative probabilities of treatment discontinuation were 10.5% at month 12 and 16.4% at month 24.The proportions of participants with HIV RNA less than 50 copies/ml at months 12 and 24 were 99.0 and 98.6%. CONCLUSION:CAB/RPV demonstrated high virological efficacy over 2 years in a real-world setting; ISRs represented the leading cause of discontinuation.
OBJECTIVE:To examine temporal trends in reasons for stopping preexposure prophylaxis (PrEP) among MSM from 2018 to 2024, including how reasons co-occur and vary by demographics. DESIGN:Pooled repeated cross-sectional analysis of seven annual waves of the American Men's Internet Survey (AMIS), a national behavioral survey of US cisgender MSM (N = 54 612). METHODS:Among 3074 noncurrent PrEP users who reported reasons for stopping, we collapsed checklist items into six thematic categories and estimated adjusted prevalence by survey year using multivariable logistic regression with g-computation. Latent class analysis (LCA) identified subgroups with distinct discontinuation profiles. RESULTS:The most common reason was Altered Sexual Activity (55%), followed by Side Effects (31.6%) and Financial/Access (29.4%). After demographic adjustment, Altered Sexual Activity rose from 46.2% in 2018 to 61.2% in 2024 [adjusted odds ratio (aOR) 1.93], and Privacy/Discrimination roughly doubled from 5.6 to 11.3%, the only reason with a significant linear trend (aOR 1.14 per year; P = 0.003). Financial/Access remained stable at approximately 29% across all 7 years. LCA identified three classes: Changed Circumstances (35.1%), Structural Barriers (23.8%), and Clinical/Multi-Barrier (41.1%). Being uninsured was the strongest predictor of financial discontinuation (aOR 4.31). CONCLUSIONS:Over 7 years of PrEP scale-up, circumstance-driven discontinuation grew increasingly dominant while stigma-related discontinuation doubled and cost barriers persisted. Three distinct discontinuation profiles argue for tailored approaches: re-engagement pathways for those whose circumstances change, financial navigation for structural barriers, and comprehensive clinical support for those experiencing multiple challenges.
OBJECTIVES:Kidney dysfunction is increasingly recognized in children with HIV (CWH). We aimed to identify longitudinal patterns of kidney function in a hospital-based cohort. METHODS:We retrospectively analyzed estimated glomerular filtration rate (eGFR) data for up to 12 years after antiretroviral therapy (ART) initiation in CWH (aged ≤18 years) who were under active follow-up. Group-based trajectory modeling (GBTM) was used to identify eGFR trajectories. Model selection was based on Bayesian Information Criterion, log Bayes factor, entropy, significance of polynomial terms, minimum group size (≥5%), and posterior probabilities (≥0.70). Multinomial logistic regression examined associations between trajectory membership and predictors, including age at ART initiation, nutritional status, WHO stage, baseline CD4 percentage, adherence, viral load, and tenofovir use. RESULTS:Among 202 CWH (63.9% boys), age at ART initiation was 4.1 ± 3.1 years. Three trajectories were identified: static (53.5%), early-decline (34.5%), and late-decline (12.0%). The early-decline group showed a steady reduction in eGFR from early follow-up, while the late-decline group demonstrated an initial rise followed by progressive decline. Proteinuria was more frequent in both decline (adverse) trajectories. Older age at ART initiation independently predicted membership in both adverse trajectories, whereas lower baseline CD4 percentage was associated with the late-decline group. Each year delay in ART initiation increased the relative risk of early- and late-decline trajectories by 30% and 50%, respectively, although the relationship was nonlinear. CONCLUSIONS:Distinct eGFR trajectories highlight heterogeneity in kidney function among CWH. Delayed ART initiation and lower baseline CD4 percentage are associated with adverse kidney function trajectories.
OBJECTIVES:Quantify hazardous alcohol prevalence among individuals at risk of acquiring HIV and its association with sexual behaviors, and recent and undiagnosed HIV in 11 Eastern and Southern African countries. DESIGN:Secondary analysis of 16 nationally-representative household surveys (2015-2023). METHODS:We included sexually active individuals aged ≥15 years. Alcohol use patterns were classified using the AUDIT-C (non-drinkers; low-risk drinkers; hazardous non-binge drinkers; hazardous binge drinkers). Outcomes included sexual risk behaviors, recent HIV infection, and undiagnosed HIV infection. Survey-weighted alcohol use prevalence and logistic regression were estimated by gender, adjusting for sociodemographic covariates. We estimated the proportion of recent and undiagnosed infections arising from excess risks associated with alcohol use patterns. RESULTS:Analyses included 251,931 participants. Across countries, 5.8%-21.1% reported hazardous binge drinking, and 3.7%-15.7% reported hazardous non-binge drinking, with large gender differences. Sexual risk behaviors increased with drinking severity among men and women. Alcohol use was associated with higher odds of undiagnosed HIV infection; adjusted odds ratios ranged from 1.32 (1.16-1.50) for low-risk drinkers to 1.52 (1.34-1.72) for hazardous binge drinkers among men, and 1.28 (1.13-1.46) to 1.55 (1.31-1.82) among women. Removing alcohol-associated excess risk reduced undiagnosed HIV by 15.1% (10.9%-19.4%) among men and 5.8% (4.0%-7.9%) among women. Estimates for recent infections followed a similar pattern but with larger uncertainty. CONCLUSIONS:Hazardous alcohol use was associated with HIV risk in Eastern and Southern Africa. Reaching individuals with hazardous alcohol use with effective HIV prevention could reduce risk, and interventions to reduce alcohol use among heavy drinking populations may improve overall health, including HIV-related outcomes.
OBJECTIVES:Carotid atherosclerosis is an established risk factor for cognitive impairment. FDG-PET detects subtle inflammatory changes in the arterial wall that may precede plaque formation and rupture. We investigated whether carotid inflammation is associated with cognitive function and its relative importance as a predictor of concurrent cognitive function compared with other factors. DESIGN/METHODS:: In this cross-sectional study, we recruited individuals ≥40 years with undetectable viral load at moderate-to-high cardiovascular risk. Participants underwent FDG-PET, stress and cognitive assessments. We used pairwise partial correlations to identify significant associations between arterial inflammation and cognition. We applied a machine learning analysis workflow to evaluate the ability of carotid inflammation alone, and in combination with other factors, to predict cognition. RESULTS:Among 47 people, carotid inflammation was independently correlated with global cognition [r = -0.405, 95% confidence interval (CI) -0.618 to -0.100, P = 0.007]. In the machine learning analysis, the probability of carotid inflammation predicting cognitive function within one standard deviation of the true value was 68% (95% CI 52-80). The predictive accuracy improved marginally when individual cardiometabolic factors were added to the model (73%, 95% CI 57-84). When all potential variables were considered, predictive accuracy improved substantially (85%, 95% CI 71-93), with carotid inflammation remaining as the most important cardiometabolic predictor of cognitive function. CONCLUSION:Carotid inflammation on FDG-PET outperformed most other factors in predicting concurrent cognitive function and provided unique predictive information beyond traditional cardiometabolic risk factors. Future longitudinal studies should examine whether carotid inflammation predicts incident cognitive impairment, which would support its use as a clinical risk marker in people with HIV.
To assess whether the coronavirus disease 2019 (COVID-19) pandemic altered the clinical composition of HIV/AIDS–related deaths in Peru, distinguishing HIV/AIDS-only deaths from HIV/AIDS-COVID deaths and examining indicators of advanced HIV disease and opportunistic infections (OIs). Nationwide retrospective observational study using the onset of COVID-19 as an exogenous shock within a natural–experiment framework. Triangulation was performed across interrupted time series, ecological, and individual-level analyses. Individual-level mortality records from Peru's National Death Registry (January 2017–December 2024) were analyzed. HIV/AIDS-related deaths were identified using ICD-10 codes and text terms and classified as HIV/AIDS-only or HIV/AIDS-COVID. Segmented interrupted time series models estimated changes in monthly proportions of clinical indicators among HIV/AIDS-only deaths. Ecological models examined relationships between the monthly share of HIV/AIDS-COVID deaths and patterns in HIV/AIDS-only deaths. Multivariable regressions compared individual-level clinical characteristics during 2020–2024. The onset of COVID-19 coincided with abrupt declines in documentation of severe immunosuppression and OI among HIV/AIDS-only deaths. Months with a higher share of HIV/AIDS-COVID deaths were associated with lower prevalence of advanced HIV indicators among HIV/AIDS-only deaths. Individually, HIV/AIDS-COVID deaths showed slightly higher prevalence of advanced HIV disease but lower prevalence of OIs, whereas HIV/AIDS-only deaths more often reflected complex HIV-related pathology. The COVID-19 pandemic reconfigured the clinical composition of HIV/AIDS-related mortality in Peru, concentrating HIV/AIDS-only deaths among individuals with more advanced disease while generating a distinct profile of HIV/AIDS-COVID co-infection. Strengthening diagnostic capacity, continuity of HIV care, and integrated surveillance is essential to protect people living with HIV during future health-system shocks.
