AIDS最新文献

{"title":"Temporal trends in viral setpoint and peak CD4 + cell count soon after HIV-1 seroconversion.","authors":"Nikos Pantazis, Caroline Sabin, Dominique Costagliola, Sophie Grabar, Christina Carlander, John Gill, Ard van Sighem, Inma Jarrin, Laurence Meyer, Elisa Ruiz-Burga, Shema Tariq, Bruno Spire, Fiona Burns, Giota Touloumi","doi":"10.1097/QAD.0000000000004527","DOIUrl":"10.1097/QAD.0000000000004527","url":null,"abstract":"<p><strong>Objectives: </strong>To examine whether HIV-1 virulence, as measured by prognostic markers soon after seroconversion, has changed over time and across subgroups in the context of widespread ART availability.</p><p><strong>Design: </strong>Observational cohort study of individuals with well estimated HIV-1 seroconversion dates recruited from clinics in eight European countries and Canada (CASCADE Collaboration).</p><p><strong>Methods: </strong>We analyzed data from 21 933 participants who seroconverted 1980-2014, while ART-naïve and AIDS-free. Piecewise linear mixed models with one knot at 1 year after seroconversion for log 10 HIV-1 RNA (setpoint viral load, SPVL) and 4 months for square-root CD4 + cell count (peak CD4) were fitted. Models adjusted for age, sex/probable exposure route, region of origin, diagnosis during acute infection, and assay type.</p><p><strong>Results: </strong>SPVL increased and peak CD4 declined over time until approximately 2000, then stabilized, with a mild reversal after 2005. Estimated (95% CI) average SPVL for those seroconverting on 1/1/1980, 1/1/1995, 1/1/2005, and 31/12/2014 was 3.2 (3.0-3.4), 4.0 (3.9-4.1), 4.3 (4.2-4.4), and 4.2 (4.1-4.3) log10 copies/ml, respectively. Corresponding estimates for peak CD4 were 960 (898-1025), 615 (584-648), 521 (492-551), and 560 (526-594) cells/μl. The increase in SPVL up to 2005 was less pronounced in European/North American MSM (1.0 log 10  copies/ml) than in men and women with heterosexual exposure from the same region or from Africa (1.5 and 1.4 log 10  copies/ml, respectively).</p><p><strong>Conclusions: </strong>SPVL and peak CD4 stabilized by 2000-2005, consistent with HIV-1 adaptation to the population. The subsequent trend reversal, most evident among MSM, warrants ongoing monitoring.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1346-1354"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13566474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex dynamics between internalized HIV stigma, depression, and anxiety with panic among people with HIV.","authors":"Lydia N Drumright, Heidi M Crane, Rob J Fredericksen, Bridget M Whitney, Edward Cachay, Kenneth H Mayer, Katerina Christopoulos, Sonia Napravnik, Richard D Moore, Jeanne C Keruly, Geetanjali Chander, Mallory O Johnson, Michael S Saag, Torsten B Neilands, Timothy Crawford, Oluwaseun Falade, Mari M Kitahata, Laura Bamford, George Yendewa, Joseph A C Delaney, Simon D W Frost","doi":"10.1097/QAD.0000000000004525","DOIUrl":"10.1097/QAD.0000000000004525","url":null,"abstract":"<p><strong>Background: </strong>Previous studies suggest that internalized HIV stigma (IHS) results in HIV viral nonsuppression via directly increasing depression, which then reduces adherence leading to nonsuppression; however, the dynamics between IHS and mental health are likely more complex. We sought to better understand IHS-mental health dynamics using data from a longitudinal clinical cohort of people with HIV (PWH) receiving healthcare across 10 US primary care clinics.</p><p><strong>Methods: </strong>Among 8,506 PWH who had ≥2 timepoints in which IHS, depression, and anxiety were measured, we examined changes over time in both two-state (i.e., impact of IHS on depression or anxiety and vice versa) and four-state combinations of depression-IHS (i.e., no depression or IHS, depression/no IHS, no depression/IHS, both depression/IHS) and anxiety-IHS. Transition probabilities between states and factors influencing transitions were identified using multistate Markov models.</p><p><strong>Results: </strong>The impact of IHS on the transition rates of mental health measures (i.e., depression, anxiety) and vice versa were almost the same, suggesting that each influences the other. Over 50% of PWH remained in the same IHS-depression or IHS-anxiety state. PWH with IHS had almost twice the rate of transitioning from no depression/anxiety to having depression/anxiety compared to PWH without IHS; with similar results for the depression or anxiety with no IHS to reporting IHS transition.</p><p><strong>Conclusions: </strong>We demonstrate that IHS and mental health dynamics are more complex than previously suspected and that the associations are bidirectional, which has implications for both future analyses and optimal management of these conditions among PWH.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1355-1364"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13224847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Community PrEP delivery preferences among pregnant and breastfeeding women using oral PrEP in South Africa and Kenya.","authors":"Nafisa J Wara, Rufaro Mvududu, Mary M Marwa, Laurén Gómez, Nyiko Mashele, Catherine Orrell, John Kinuthia, Grace John-Stewart, Landon Myer, Risa Hoffman, Jillian Pintye, Dvora L Joseph Davey","doi":"10.1097/QAD.0000000000004528","DOIUrl":"10.1097/QAD.0000000000004528","url":null,"abstract":"<p><strong>Objective: </strong>We evaluated preferences for differentiated service delivery of oral preexposure prophylaxis (PrEP) versus clinic pick-up among oral PrEP-experienced pregnant and breastfeeding women (PBFW) in South Africa and Kenya.</p><p><strong>Design and methods: </strong>From September 2021 to February 2022, we surveyed PBFW in oral PrEP studies in South Africa and Kenya. We asked participants about their PrEP delivery preferences and used logistic regression models adjusted for age and country to identify predictors of preferring community over clinic-based PrEP delivery.</p><p><strong>Results: </strong>We surveyed 394 South African and Kenyan PBFW (73% postpartum, median age 28 years). Overall, 59.5% of South African participants ( n  = 113) and 24.5% of Kenyan participants ( n  = 50, P  < 0.01) were interested in community PrEP delivery, most frequently due to convenience ( n  = 80, 49.1%) and lower transportation costs ( n  = 78, 47.9%). Participants preferred clinic PrEP pick-up due to privacy ( n  = 174, 75.3%) and desire to see a healthcare provider ( n  = 83, 35.9%). Preference for community PrEP delivery was positively associated with South African participants [adjusted odds ratio (aOR) = 4.32, 95% confidence interval (CI) = 2.80-6.67], PrEP stigma (aOR = 2.59, 95% CI = 1.58-4.23), completing secondary school or higher (aOR = 1.84, 95% CI = 1.17-2.92), and transportation cost to clinic (aOR = 1.39, 95% CI = 1.10-1.75). Preference of community PrEP delivery was negatively associated with age (aOR = 0.68 per 10-year increase, 95% CI = 0.49-0.95) and having one or more sexual partners versus no sexual partners (aOR = 0.34, 95% CI = 0.12-0.95).</p><p><strong>Conclusions: </strong>Oral PrEP-experienced PBFW in South Africa and Kenya described varied preferences for community PrEP delivery. Associations with community-based PrEP delivery preference identified in this analysis may be useful in the development of context-specific DSD interventions targeting PBFW.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1337-1345"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-exposure prophylaxis surfing: rethinking partner-dependent HIV prevention strategies among MSM.","authors":"Bruno Spire","doi":"10.1097/QAD.0000000000004550","DOIUrl":"10.1097/QAD.0000000000004550","url":null,"abstract":"","PeriodicalId":7502,"journal":{"name":"AIDS","volume":"40 9","pages":"1397-1398"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HIV immunological nonresponders show low SKAP1 concentration and DNA hypermethylation in the SKAP1 promotor region.","authors":"Wilhelm A J W Vos, Suzanne D E Ruijten, Xun Jiang, Nienke van Unen, Willem van Snippenberg, Albert L Groenendijk, Marc J T Blaauw, Louise E van Eekeren, Nadira Vadaq, Hanneke Maas, Malin Östman, Maartje C P Cleophas, Kees Brinkman, Jan van Lunzen, Willem L Blok, Janneke E Stalenhoef, Yang Li, Mihai G Netea, Linos Vandekerckhove, Jéssica C Dos Santos, Vasiliki Matzaraki, Cheng-Jian Xu, Andre J A M van der Ven","doi":"10.1097/QAD.0000000000004529","DOIUrl":"10.1097/QAD.0000000000004529","url":null,"abstract":"<p><strong>Objective: </strong>The aim of this study was to improve understanding of biological pathways underlying inadequate CD4 + T-cell restoration after initiating antiretroviral treatment as these so called Immunological nonresponders are at increased risk for morbidity and mortality while treatment options are lacking.</p><p><strong>Design: </strong>We compared baseline multiomics data from 88 Immunological nonresponders and 1467 immunological responders that participated in the 2000HIV study, separated into a discovery and validation cohort.</p><p><strong>Methods: </strong>We measured expression levels of 2367 plasma proteins, comparing the immunological responders and nonresponders. As this highlighted low Src kinase-associated phosphoprotein 1 (SKAP1) levels in Immunological nonresponders, we measured intracellular SKAP1 levels in CD4 + T-cells, investigated DNA methylation and assessed single-nucleotide polymorphisms (SNPs). We also explored whether HIV or CMV infection may influence SKAP1 expression.</p><p><strong>Results: </strong>SKAP1 plasma levels were significantly lower in Immunological nonresponders in both cohorts. SKAP1 plasma concentrations reflected intracellular levels in CD4 + T-cells. DNA methylation analysis showed significant hypermethylation at the SKAP1 promotor region. Three SNPs close to the SKAP1 gene were associated with poor Immunological response. Preliminary data suggest that HIV or CMV may influence SKAP1 levels.</p><p><strong>Conclusion: </strong>Our data show decreased SKAP1 concentrations in immunological nonresponders, potentially driven by hypermethylation of the SKAP1 promoter. Downregulation of SKAP1, which is known to play a role in T cell proliferation and migration, may therefore contribute to the poor restoration of CD4 + cell count after ART.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1225-1235"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13566367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147759688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early-treated children with perinatal HIV show elevated monocyte activation into late childhood.","authors":"Claire R Davies, Tariq R Webber, Sahera Dirajlal-Fargo, Nicholas T Funderburg, Patrick J D Bouic, Kennedy N Otwombe, Mark F Cotton, Sara H Browne, Steve Innes, Florin A Vaida","doi":"10.1097/QAD.0000000000004505","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004505","url":null,"abstract":"<p><p>Early ART initiation in children with perinatal HIV (CHIV) greatly improves long-term outcomes. However, little is known of the long-term inflammatory profile. Our longitudinal study compared 26 inflammatory markers in early treated CHIV and HIV-unexposed children. CHIV displayed extensive immune marker elevations, clustered around monocyte activation. Despite early-antiretroviral therapy and sustained viral suppression, these children are at increased risk of non-communicable diseases.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":"40 9","pages":"1399-1402"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148617986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Renal outcomes with dolutegravir plus lamivudine versus bictegravir/emtricitabine/tenofovir alafenamide in ART-naive adults with HIV.","authors":"Dian Zhao, Liqin Sun, Ping Cen, Yun He, Fang Zhao, Xiaorui Li, Yinsong Luo, Xi Xiao, Chenye Liu, Yuxin Jiang, Hui Wu, Weijie Gong, Yanjun Li, Jiaye Liu","doi":"10.1097/QAD.0000000000004535","DOIUrl":"10.1097/QAD.0000000000004535","url":null,"abstract":"<p><strong>Objective: </strong>Dolutegravir plus lamivudine (DTG + 3TC) and bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) are guideline-recommended first-line regimens for people with HIV (PWH), but their comparative renal safety remains unclear. We aimed to compare kidney outcomes between these regimens in antiretroviral therapy (ART)-naive PWH, stratified by baseline renal function.</p><p><strong>Methods: </strong>We conducted a multicenter, prospective cohort study in China (2018-2025) enrolling 2655 ART-naive PWH initiating DTG + 3TC ( n = 788) or BIC/FTC/TAF ( n = 1867). Participants were stratified by baseline estimated glomerular filtration rate (eGFR; <90 versus ≥90 ml/min/1.73 m 2 ). Stabilized inverse probability of treatment weighting was applied to evaluate incident chronic kidney disease (CKD) and longitudinal eGFR changes over 24 months.</p><p><strong>Results: </strong>Among participants with baseline creatinine-based eGFR (eGFRcreat) <90 ml/min/1.73 m 2 , DTG + 3TC was associated with greater declines in eGFRcreat compared with BIC/FTC/TAF at 12 and 24 months. In contrast, no significant differences were observed when kidney function was assessed using the cystatin C-based or creatinine-cystatin C-based equation. In the eGFRcreat ≥90 ml/min/1.73 m 2 stratum, trajectories were comparable. CKD incidence was comparable between regimens in both strata (eGFRcreat <90 ml/min/1.73 m 2 : 29.9% versus 16.8%; ≥90 ml/min/1.73 m 2 : 5.1% versus 4.7%; both P > 0.05), and adjusted Cox models showed no significant difference in CKD risk.</p><p><strong>Conclusion: </strong>DTG + 3TC and BIC/FTC/TAF showed comparable renal safety over 24 months among ART-naive PWH. However, when a decline in eGFRcreat is observed during DTG treatment, cystatin C-based assessment may help clarify true kidney function.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":"1261-1270"},"PeriodicalIF":2.9,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13566468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LDL-C target achievement in people living with HIV: impact of combination lipid-lowering therapy. A retrospective cohort analysis.","authors":"Marcella Manicardi, Jovana Milic, Giuseppe Esposito, Marianna Menozzi, Giuseppe Mancini, Gian Luca Cuomo, Lorenzo Benassi, Elisabetta Delmonte, Severino Ambrosio, Cristina Mussini, Giuseppe Boriani, Giovanni Guaraldi","doi":"10.1097/QAD.0000000000004594","DOIUrl":"10.1097/QAD.0000000000004594","url":null,"abstract":"<p><strong>Background: </strong>Real-world low-density lipoprotein cholesterol (LDL-C) target attainment remains low in people with HIV (PWH). Updated ESC/EAS 2025 guidelines underscore the need to reassess treatment patterns in clinical practice.</p><p><strong>Methods: </strong>Retrospective observational longitudinal study including PWH ≥40 years, evaluated twice between 2020 and 2025 at the Modena HIV Metabolic Clinic, with complete laboratory and clinical follow-up data. Objective was to evaluate the real-world use and effectiveness of different lipid-lowering therapy (LLT) regimens in achieving guideline-based LDL-C targets.</p><p><strong>Results: </strong>Among 588 PWH (71.8% male), median age was 60 years (IQR 56-64) and 97.4% had suppressed HIV viral load. According to cardiovascular (CV) risk classification, 29.3% were at moderate risk, 52% at high risk, 12.4% at very high risk and 6.3% at extreme risk. LDL-C target attainment increased from 19.6% at baseline to 28.8% at follow-up. Achievement rates declined with increasing CV risk. In multivariable analysis, combination LLT was the strongest predictor of LDL-C target attainment (odds ratio 5.7, 95% confidence interval 3.7-9.0, P  < 0.0001), whereas statin dose escalation was not. Diabetes was also associated with greater odds of reaching LDL-C goals.</p><p><strong>Conclusions: </strong>LDL-C control remains suboptimal in PWH, particularly among those at higher cardiovascular risk. Combination lipid-lowering therapy markedly increases the likelihood of achieving LDL-C targets, supporting broader adoption of combination strategies in routine HIV care.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148786944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral suppression in models of care for improving engagement of antiretroviral therapy in postpartum women living with HIV.","authors":"Mustafa Shuaib, Jasantha Odayar, Tamsin K Phillips, Thokozile R Malaba, Elaine J Abrams, Landon Myer","doi":"10.1097/QAD.0000000000004603","DOIUrl":"https://doi.org/10.1097/QAD.0000000000004603","url":null,"abstract":"<p><strong>Objective: </strong>To compare viral suppression between two models of care [adherence club and integrated maternal and child healthcare (MCH)] for improving engagement of postpartum women with HIV (WWH) to antiretroviral therapy (ART).</p><p><strong>Design: </strong>Individual participant data network meta-analysis (IPD-NMA) of two randomized controlled trials in Cape Town, South Africa [Postpartum Adherence Clubs for Antiretroviral Therapy (PACART) comparing adherence clubs to standard of care (primary healthcare ART clinics, SOC), and MCH-ART comparing integrated MCH for the duration of breastfeeding to SOC].</p><p><strong>Methods: </strong>One-step IPD-NMA using generalized linear mixed effects models was performed to indirectly compare viral suppression (viral load<50 copies/ml) between adherence clubs and integrated MCH at 6 and 12 months postpartum, linked by SOC as a comparator.</p><p><strong>Results: </strong>Overall, 882 women were included: 471 enrolled in MCH-ART and 411 in PACART. In MCH-ART, 87 and 79% of women in intervention arm had viral suppression at 6 and 12 months postpartum, compared to 70 and 54% in SOC. In PACART, 87 and 74% of women had viral suppression at 6 and 12 months in intervention arm, compared to 79 and 67% in SOC. Adjusting for age, parity, socioeconomic status, tuberculosis (TB) history, HIV diagnosis time, ART duration, and viral load less than 400 copies/ml at enrolment, relative odds of viral suppression in integrated MCH versus adherence clubs were 2 [95% confidence interval (CI): 0.88-4.53] at 6 months and 2.89 (CI: 1.42-5.90) at 12 months.</p><p><strong>Conclusion: </strong>In this setting, an integrated MCH model for delivering ART postpartum achieved higher levels and more sustained effect on viral suppression compared to adherence clubs, a popular differentiated service delivery (DSD) model for ART.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct associations of peripheral mtDNA copy number and bioenergetic function with cognition in women with HIV and psychiatric comorbidities.","authors":"Hannah Stadtler, Leah H Rubin, Gretchen N Neigh","doi":"10.1097/QAD.0000000000004597","DOIUrl":"10.1097/QAD.0000000000004597","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":7502,"journal":{"name":"AIDS","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}