AIDS

BackgroundDespite effective antiretroviral therapy, HIV-1 remains a global health challenge. Most people living with HIV (PWH) are diagnosed in the chronic stage and around half globally are diagnosed late. Within the group with a chronic diagnosis, insight into the effect of time of therapy initiation on reservoir dynamics and immune reconstitution from diagnosis onwards is limited. MethodsIn this prospective cohort study of PWH diagnosed during the chronic stage (from Fiebig VI) were stratified into late (<350 CD4+ T cells/mm3 or an AIDS-defining illness) or non-late diagnosis groups. We analyzed the viral reservoir by IPDA, SQuHIVLa and FISH-Flow, and the immune compartment with the AIM assay and a 45-color spectral flow cytometry panel in the first year after ART initiation. FindingsAlthough proviral DNA decreased in the first year of ART, the inducible reservoir remained stable. PWH with a late diagnosis had a significantly higher inducible reservoir and lower CD4+ T-cell counts than the non-late HIV diagnosis group. A year after ART initiation, the group with a late diagnosis showed a higher abundance of exhausted CD8+ T cells, higher expression of activation/exhaustion markers, and a lower naive CD4+ T-cell abundance than the non-late diagnosis group. Moreover, activation and exhaustion marker expression on T cells correlated significantly with CD4+ T cell count pre-ART. InterpretationOur results show that late diagnosis is associated with a persistently higher inducible viral reservoir and impaired immune recovery. These findings underline the importance of early diagnosis and treatment, and rationalize the use of late diagnosis as a covariate in future studies. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSPrior research has demonstrated that initiation of antiretroviral therapy (ART) during the acute stage of HIV-1 infection limits reservoir seeding, reduces immune activation and preserves immune function. Therefore, studies have focused on reservoir and immune dynamics in this acutely diagnosed group. However, only 8,4% of diagnoses in Europe are made at an acute stage. Despite the fact that the far majority of diagnoses are made at chronic infection, heterogeneity within this group has been overlooked. In clinical settings, late HIV-1 diagnosis, defined as CD4+ T cell count <350 or AIDS-defining illness, has been shown to lead to more opportunistic infections, slower time to viral suppression and increased mortality when compared to a non-late (but still chronic) diagnosis. Yet, the reservoir and immune dynamics in these groups remains poorly characterized. Added value of this studyIn this study, PBMCs from a prospective cohort of people with a chronic HIV diagnosis in the first year after ART initiation were analyzed using integrated approaches - reservoir quantification and in depth immunophenotyping to simultaneously characterize reservoir dynamics and the immune compartment. We show a significant decrease in the intact viral reservoir for all participants within the first year of ART, whereas the inducible reservoir remained stable. A comparison was performed between the group with late and non-late (but still chronic) diagnosis, shedding light on the heterogeneity within the chronic diagnosis group. The late diagnosis group had a significantly higher inducible reservoir and immune exhaustion, both in marker expression as well as exhausted T cell abundance. All but four of these activation and exhaustion markers differentially expressed between the two groups correlate with CD4+ T cell count pre-ART, highlighting the large heterogeneity in this group. Implications of all the available evidenceTogether, these findings provide insight into the reservoir and immune dynamics within the first year after ART initiation. The data can especially inform both reservoir-targeting strategies that intervene at or shortly after ART initiation, as well as strategies that aim to harness the immune system. Moreover, these results reinforce the importance of early diagnosis, even after the acute stage. The differences in the reservoir and immune compartments between the late and non-late diagnosis groups underscore the need for the use of late diagnosis or time to diagnosis as a covariate in future cure studies.

Human immunodeficiency virus (HIV) infection promotes considerable bioenergetic, spatially heterogenous strain to the brain that is incompletely ameliorated through viral suppression afforded by antiretroviral therapy (ART). Disrupted homeostasis of brain lipids after HIV in humans or simian immunodeficiency virus (SIV) infection in rhesus macaques occurs due to elevated energetic demands, neuroinflammation, reactive oxygen species, and barrier leakiness. Brain lipids are particularly vulnerable to HIV-associated dysregulation due to their high abundance, unique composition, and specialized functional roles. Using rhesus macaques exposed to SIV and ART (tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and dolutegravir (DTG), we investigated the spatial distribution and abundance of lipids across brain regions and metabolically relevant peripheral tissues using mass spectrometry imaging. When comparing lipid abundance, individual lipids representing a multitude of species were more varied across tissues than by treatment condition. Further, we discerned either solely SIV infection or ART outweighed one another in altering phospholipids in different tissues Presence of ART had a greater influence on phospholipid homeostasis in the temporal cortex and hippocampus than in the midbrain, possibly due to differences in penetrance and turnover of ART across brain regions. Overall, these data demonstrate ART robustly increased phospholipids across brain regions while SIV infection had a varied impact depending on the brain region. These findings inform the need to further evaluate the neurologic consequences that may result in the brain due to disrupted lipid homeostasis across ART regimens.

The global ambition to end the human immunodeficiency virus (HIV) epidemic requires understanding which system-level policy levers, enacted under the framework of Universal Health Coverage (UHC), are most effective in achieving both transmission reduction and diagnostic coverage. This study addresses an important evidence gap by quantifying the within-country association between measurable UHC policy indicators and the estimated rate of new HIV infections across nine Southeast Asian countries between 2013 and 2022. Employing a Fixed-Effects panel data methodology, the analysis controls for time-invariant national heterogeneity, ensuring reliable estimates of policy impact. We found that marginal changes in total current health expenditure (CHE) as a percentage of gross domestic product (GDP) were not statistically significantly associated with changes in HIV incidence. However, increases in the UHC Infectious Disease Service Coverage Index were statistically significantly associated with concurrent reductions in HIV incidence (p < 0.001), suggesting the efficacy of targeted service implementation as the principal driver of curbing new HIV infections. In addition, the UHC Reproductive, Maternal, Newborn, and Child Health Service Coverage Index exhibited a statistically significant positive association with changes in HIV incidence (p < 0.01), which is interpreted as a vital surveillance artefact resulting from expanded detection and reporting of previously undiagnosed HIV cases. Furthermore, out-of-pocket (OOP) health expenditure as a percentage of CHE showed a counter-intuitive negative association with changes in HIV incidence (p < 0.01), suggesting this metric primarily shows ongoing indirect cost burdens on the established patient cohort, or, alternatively, presents a diagnostic access barrier that results in lower case finding. These findings suggest that policymakers should prioritise investment in targeted infectious disease service efficacy over aggregate fiscal commitment and utilise integrated sexual health platforms for strengthened HIV surveillance and case identification.

Objectives: This systematic review and meta-analysis (2010 - 2025) examines changes in uptake and retention rates among pregnant and postpartum women with HIV in sub-Saharan Africa as countries adopted Option B+ for preventing vertical transmission. Design and data sources: We searched PubMed, Embase, Cochrane Library, Scopus, and African Index Medicus from 10/2021 - 05/2025 for eligible studies that measured HIV care uptake or retention for pregnant/postpartum women under prevention policies before or during Option B+. Study designs were limited to cohort, case-control, cross-sectional, or interventional studies. Exclusions were white papers, commentaries, modeling, cost-effectiveness, and qualitative studies. Data extraction and synthesis: Outcomes were (i) HIV care uptake defined as initiation of ART during pregnancy or prior to initial antenatal care (ANC) visit and (ii) proportion of women retained in HIV care as defined by study authors after ART initiation (or entry to antenatal care). These were synthesized in meta-analyses stratified by policy era (pre-Option B+ vs. Option B+) at different times for different countries. Comparisons between policy eras were made using relative risk with a 95% confidence interval. Pooled retention estimates at 6- and 12-months post ART initiation used crude relative risks (RR) with 95% confidence intervals (CI). Results: Among 4,752 articles, 82 from 17 countries were included; 60 reported HIV care uptake, 31 reported retention outcomes. Pooled HIV uptake rose by 8% (RR=1.08; 95% CI:1.06-1.09) and pooled retention in HIV care rose by 46% (RR=1.46; 95% CI:1.41-1.51) after Option B+ implementation. Pooled estimates of retention in care were 36.9% (95% CI: 13.9%, 59.9%) at 6 months post ART initiation before the implementation of Option B+ and 72.7% (95% CI: 66.3%, 79.1%) after implementation. Conclusion: HIV care uptake and retention improved after Option B+ implementation in 15 countries reporting results, but retention remains suboptimal for meeting UNAIDS 95-95-95 targets.

Objectives: Quantify hazardous alcohol consumption prevalence among individuals at risk of acquiring HIV infection and its association with high-risk sexual behaviors and incident HIV in 11 Eastern and Southern African countries. Design: Secondary analysis of 16 nationally-representative household surveys (2015-2023). Methods: The study included sexually active individuals aged [&ge;]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 high-risk sexual behaviors, recent HIV infection, and undiagnosed HIV infection. Survey-weighted alcohol use prevalence and logistic regression were estimated by gender, adjusting for sociodemographic covariates. Model outputs were used to estimate change in incident infections when removing 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. Compared with non-drinkers, 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. Simulated removal of 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 HIV infection followed a similar pattern but with larger uncertainty. Conclusions: Hazardous alcohol use was associated with sexual risk and HIV infection in Eastern and Southern Africa. Reaching individuals who use alcohol with effective HIV prevention may reduce HIV acquisition risk across the region.

Clonal hematopoiesis of indeterminate potential (CHIP) is an age-associated condition linked to chronic inflammation and an increased risk of cardiovascular diseases and hematological malignancies. People with HIV (PWH) exhibit a higher prevalence of CHIP than the general population, but the mechanisms underlying this association remain unclear. In particular, it is unknown whether the excess burden of CHIP reflects earlier emergence of mutant clones, altered clonal expansion dynamics, or differences in selective pressures acting on hematopoietic stem cells. We reconstructed longitudinal trajectories of CHIP variant allele frequency (VAF) in 52 PWH using serial peripheral blood samples spanning up to 25 years from the Swiss HIV Cohort Study. We used spline-based modelling to estimate clone size and growth dynamics, and dynamic time warping to identify common trajectory patterns. Associations between clonal dynamics and longitudinal immune parameters were assessed using linear mixed-effects models. Trajectories in PWH were compared with publicly available longitudinal CHIP data from the SardiNIA population cohort. We identified heterogeneous clonal dynamics consistent with known gene-specific fitness patterns. Larger clone size was associated with lower CD4 T-cell count and lower CD4/CD8 ratio. Compared with the general population cohort, PWH showed higher VAF across the observed age range and steeper early trajectory increases, while long-term expansion rates were broadly similar. Greater variability in clonal dynamics among PWH suggests a stronger contribution of host environmental factors to clonal fitness. These findings support a model in which HIV-associated immune dysregulation alters the hematopoietic fitness landscape, contributing to earlier detectable clonal expansion and increased burden of CHIP in PWH.

BackgroundART effectively suppresses HIV replication and restores CD4+ T cells; however, long-lived HIV latent reservoirs enable viral persistence. Tuberculosis (TB) co-infection further impacts HIV latency and enhances viral replication. Given the high prevalence of latent TB infection (LTBI) in TB-endemic settings, understanding its impact on HIV biology is critical. Our study aims to investigate the influence of TB co-infection on HIV reservoir dynamics, viral diversity, and drug resistance mutations in ART-naive individuals. MethodologySamples from 90 ART-naive HIV-1C individuals, stratified based on IGRA and TB diagnosis, were used in this study. Plasma and PBMCs were isolated for viral RNA and DNA extraction respectively. Total proviral DNA was quantified using gag PCR. Full-length env and pol genes were amplified, purified and sequenced using ONT and Illumina platforms. Pol sequences were subjected to Drug Resistance Mutation (DRM) analysis via Stanford HIVdb with a minimum threshold mutation frequency of [&ge;]10%. Full length env sequences were used for phylogenetic analysis by aligning with Indian Subtype C reference sequence and phylogenetic tree was generated using ggplot2. ResultProviral load analysis showed no significant differences across HIV+LTBI-, HIV+LTBI+, and HIV+TB+ groups, although a trend toward higher levels was observed in HIV+TB+ individuals. Correlation analysis revealed distinct immune associations, with HIV+LTBI+ individuals showing positive correlations with activation and PD-1 expression. Longitudinal analysis of proviral loads demonstrated a modest decline in proviral load post-ART but remained persistent for up to 18-20 months following initiation of ART accompanied by low level ongoing viral replication. DRM analysis revealed a 33% prevalence in ART-naive individuals, with higher occurrence in HIV+LTBI+ group. Of the identified DRMs, 38% (5/13) and 71% (5/7) in sequences obtained from PBMC and plasma respectively were attributed to polymorphic mutations associated with Integrase strand transfer inhibitors (INSTIs). DRMs within plasma and PBMC derived viruses showed high concordance. Phylogenetic analysis of env sequences indicated overlapping viral populations between the 3 groups, with greater diversity in PBMCs compared to plasma. ConclusionThe study highlights that HIV reservoir dynamics, drug resistance, and viral diversity are significantly influenced by TB co-infection. While proviral loads were comparable, LTBI-associated immune activation and granuloma niches may have driven viral diversification and DRM emergence. High concordance between compartments and presence of transmitted resistance underscore the need for baseline screening, multi-compartment analysis, and sustained surveillance.

BackgroundAdolescents and young adults with perinatally acquired HIV (APHIV) face complex psychosocial and structural challenges that may undermine resilience, a modifiable psychosocial determinant of treatment engagement, and health outcomes. Evidence on peer-led interventions targeting resilience among APHIV in South Asia remains limited. We evaluated resilience and its correlates among participants in the ImPossible Fellowship, a peer-led mentorship intervention in India. MethodsWe conducted a cross-sectional evaluation of 216 APHIV following completion of the 24-month ImPossible Fellowship in southern India in 2024. Surveys administered by trained youth investigators assessed sociodemographic, educational, and clinical characteristics. Resilience was measured using the Child and Youth Resilience Measure-Revised (CYRM-R), a validated multidimensional tool capturing personal and relational resilience dimensions. Low resilience was defined as CYRM-R threshold score [&le;]33rd percentile. Multivariate logistic regression identified independent correlates of low resilience, and sensitivity analyses explored alternative CYRM-R thresholds. ResultsParticipants had a mean age of 18.7 years (range 9-24); 50% had no surviving parents, and 43% lived in child care institutions. Median resilience scores were high (74, Interquartile range [IQR] 69-78), and 91% achieved viral suppression. In multivariate analyses, three factors were independently associated with low resilience: loss of both parents (adjusted odds ratio [aOR] 4.35, 95% CI 2.09-9.06), school discontinuation (aOR 2.43, 95% CI 1.10-5.34), and self-reported communication barriers at HIV clinics (aOR 5.83, 95% CI 2.69-12.64). These associations were consistent across sensitivity analyses at alternative resilience thresholds. At the most stringent threshold of low resilience (CYRM-R score [&le;]15th percentile), unsuppressed viral load also emerged as a significant correlate, suggesting that treatment failure may be concentrated among those with the most severely compromised resilience. ConclusionsAPHIV participating in a peer-led mentorship program demonstrated high overall resilience and viral suppression, but also revealed addressable vulnerabilities mapping to specific programmatic priorities. Peer-led models offer a promising foundational platform; however, complementary structural and psychosocial enhancements targeting these modifiable determinants are essential to optimize outcomes for those facing the greatest cumulative adversity.

Medical male circumcision (MMC) is an established HIV prevention intervention, yet concerns persist that circumcised men may adopt higher-risk sexual behaviours following the procedure. Evidence from observational studies has been inconsistent, partly because many analyses do not adequately distinguish behaviours that occur before circumcision from those that occur afterward. This study assessed the association between MMC and subsequent sexual behaviours while demonstrating how population-based cross-sectional survey data can be adapted to address this temporal challenge. We analysed nationally representative data from the 2024 Zambia Demographic and Health Survey (ZDHS), including men aged 15 - 59 years who reported their circumcision status. Men who had undergone medical circumcision were compared with uncircumcised men using a matched pseudo-cohort framework that reconstructed temporal ordering based on age at circumcision. Propensity score overlap weighting was applied to improve comparability between circumcised and uncircumcised men, and odds ratios were estimated using logistic regression models incorporating overlap weights and accounting for the complex survey design. Sexual behaviour outcomes occurring after circumcision included condom non-use at last sexual intercourse, multiple sexual partners in the past 12 months, self-reported sexually transmitted infection (STI) symptoms, and composite measures of sexual risk behaviour. The analysis included 9,609 men, of whom 33.3% were medically circumcised. MMC was associated with lower odds of condom non-use at last sexual intercourse (adjusted odds ratio [aOR] = 0.75, 95% confidence interval [CI]: 0.67 - 0.85) and lower odds of reporting any sexual risk behaviour (aOR = 0.83, 95% CI: 0.72 - 0.95). No meaningful associations were observed between MMC and reporting multiple sexual partners, self-reported STI symptoms, or higher levels of composite sexual risk behaviour. In this population-based study, MMC was not associated with sexual risk compensation under routine programme conditions within the overlap population defined by the weighting scheme, supporting the behavioural safety of MMC and illustrating the value of explicitly addressing temporality when analysing behavioural outcomes using cross-sectional survey data.

BackgroundIn the course of testing mAb-based therapies to eradicate the persistent reservoir of HIV infection, we investigated the efficacy and mode of killing of HIV-infected cells by two categories of cytotoxic immunoconjugates (CICs) targeted by the same mAb, an immunotoxin (IT) and antibody-drug conjugate (ADC). MethodsWe performed metabolic and transcriptional analyses of treatment effects on the persistently-infected cell line H9/NL4-3. Cells were treated with CICs consisting of the anti-gp41 mAb 7B2 conjugated to either deglycosylated ricin A chain (dgA) or to the highly cytotoxic anthracycline derivative PNU-159682. At intervals up to 24 hr, intracellular metabolites were quantified by 1H nuclear magnetic resonance spectroscopy, and the transcriptome analyzed by RNA-Seq. ResultsSix hr post treatment, 7B2-dgA elicited both metabolic and transcriptional alterations, whereas 7B2-PNU treated cells did not differ from untreated cells. 7B2-dgA treated cells exhibited elevated intracellular levels of many amino acids, and activation of gene pathways for apoptosis, intracellular signaling, and immune activation. By 24 hr, both 7B2-dgA and 7B2-PNU treated cells differed markedly from untreated. Many of the changes observed following 7B2-PNU treatment at 24 hr were similar to those observed at 6hr following 7B2-dgA, likely indicating processes involved in cell death, but a number of alterations were unique to either IT or ADC treated cells. ConclusionsAn IT and ADC showed both similarities and differences in their cytotoxic effects. These results raise the question of whether the mode of cell killing could be a determinant of clinical efficacy. Although these studies were aimed at targeting the persistent reservoir of HIV infection, they have relevance for the design of CICs to treat cancer and other conditions. SUMMARYThe use of cytotoxic immunoconjugates, wherein an antibody is attached to a cellular poison, is effective in the treatment of cancer and other conditions. We seek to extend these results to treating HIV and other chronic viral infections. We analyzed the molecular mechanisms of cell killing when the same antibody was attached to different toxic structures. We report that each immunoconjugate induced both common and distinct patterns of killing. Such differences may have clinical relevance.

Background: Retention to care and viral load suppression are essential components for effective HIV management, particularly among adolescents and young adults aged 15-24 years, who remain vulnerable to treatment challenges. This study aimed to assess factors associated with poor retention in care and viral load suppression among young people receiving antiretroviral therapy (ART) at Mpilo Centre of Excellence (MCoE) in Bulawayo, Zimbabwe, with the objective to guide youth-friendly interventions and improve health outcomes. Methods: A mixed methods cross-sectional study was conducted involving 110 HIV-positive youths aged 15-24 years on ART, recruited through systematic sampling and surveyed between November and December 2024. Data was collected using structured questionnaires, focus group discussions, in-depth interviews, and key informant interviews. Quantitative data were analyzed using descriptive statistics and logistic regression models to identify factors linked to viral load suppression, while qualitative data underwent thematic analysis. Results: Viral load suppression was achieved by 68.19% of participants, who met the viral suppression criterion of <50 copies/ml. Analysis identified several significant predictors via multivariable logistic regression. Younger adolescents (15-19 years) had lower odds of achieving suppression compared to older youths (20-24 years) (Adjusted Odds Ratio [AOR]: 0.81; 95% Confidence Interval [CI]: 0.67-0.97; p=0.041), while female participants demonstrated higher suppression rates than males (AOR: 0.43; 95% CI: 0.21-0.96; p=0.032). Absence of adherence challenges to ART emerged as a strong predictor of suppression (AOR: 0.12; 95% CI: 0.03-0.72; p=0.018), and perceived lack of clinical staff support was associated with a threefold higher risk of unsuppressed viral load (AOR: 3.01; 95% CI: 1.34-7.69; p=0.046). Lower treatment self-efficacy negatively impacted suppression odds (AOR: 2.65; 95% CI: 1.11-7.83; p=0.046), and lack of friend support for clinic visits reduced the likelihood of suppression (AOR: 0.31; 95% CI: 0.09-0.89; p=0.001). Qualitative findings confirmed that persistent barriers--including stigma, limited family support, economic hardship, school and work commitments--compromised both retention and adherence among adolescents and young adults. Conclusion: Younger age, male sex, ART adherence challenges, lack of clinical staff support, and lower treatment self-efficacy were significantly associated with poor viral suppression among 15-24-year-olds at Mpilo Centre of Excellence. These findings underscore the need for tailored adolescent- and youth-friendly services, enhanced adherence support, and improved treatment literacy to strengthen retention in care and viral suppression. Addressing these factors is critical for advancing progress towards UNAIDS 95-95-95 targets and reducing HIV transmission among Zimbabwean youth.

Despite of the highly potent antiretroviral therapies, HIV-1 establishes persistent infection and causes chronic inflammation in AIDS patients. Beyond CD4+ T cells, HIV-1 infects myeloid cells, including circulating monocytes and tissue-resident macrophages, and integrates with host genomes to form stable viral reservoirs. To achieve a functional HIV cure, latency-promoting agents (LPAs) have been developed for the "block-and-lock" strategy to reinforce deep HIV-1 latency and permanently silence proviruses. However, most LPAs have been tested mainly in CD4+ T cells, and their efficacy in myeloid cells remains unclear. In this study, we reported that levosimendan (LSM), a drug approved for clinic use to treat heart failures, is able to inhibit HIV lytic infection and reactivation in myeloid cells. LSM blocked viral lytic reactivation in HIV-1 latently infected monocytic cells (TH89GFP, U1) and microglial cells (HC69). LSM also inhibited HIV infection in human induced pluripotent stem cell (iPSC) derived microglia (iMG), primary human resident liver macrophages (Kupffer cells) as well as human monocyte-derived macrophages (MDMs). Furthermore, we demonstrated that overexpression of a predicted drug target of LSM, the conserved serine/threonine kinase RIOK1 (RIO kinase 1), overcomes LSMs anti-HIV effect. Overall, our studies concluded that LSM is a promising LPA to inhibit HIV-1 infection in myeloid cells in the RIOK1-dependent manner.

Long-acting cabotegravir and rilpivirine combination (LA-CAB/RPV) is approved for HIV treatment whilst long-acting cabotegravir alone (LA-CAB) is approved for HIV prevention, both in adults. However, individuals who become pregnant might prefer to discontinue it due to lack of definitive data on safety. The aim of this study was to characterise the tail-phase maternal and fetal pharmacokinetics of LA-CAB/RPV following discontinuation at steady-state early in pregnancy. A virtual population of non-pregnant women (n = 100 per scenario) initiated intramuscular injections of LA-CAB/RPV at the approved dosage and continued maintenance dose (400/600 mg once monthly or 600/900 mg once every two months) until steady state. We simulated discontinuation at steady state after only one injection during pregnancy. Tail-phase pharmacokinetics of CAB and RPV from LA injections were characterised during gestation and until 6 months postpartum. Pharmacokinetic tails of LA-CAB/RPV were driven by the residual drug in the muscle depot which stabilised at steady state and reduced steadily upon dosing discontinuation. Upon discontinuation of the monthly dosing, predicted median (IQR) maternal plasma concentrations for LA-CAB were 415 (386-448) ng/mL at delivery and 125 (115-139) ng/mL 6 months postpartum. For LA RPV, these were 11.6 (11.0-12.6) ng/mL and 7.84 (7.30-8.49) ng/mL at delivery and 6 months postpartum, respectively. Pharmacokinetic tails of LA-CAB/RPV extend to several months postpartum, with levels falling below established minimum effective concentration in most women after gestation week 33. Potential strategies to minimise potential risks associated with LA-CAB/RPV discontinuation in this population are needed.

BackgroundDespite scale-up of antiretroviral therapy (ART), children living with HIV (CLHIV) and children who are HIV-exposed-but-uninfected (CHEU) are at an increased risk of poor growth outcomes compared to children HIV-unexposed-and-uninfected (CHUU). Few studies quantify the magnitude of growth deficits extending into school age in sub-Saharan Africa (SSA). This study examined the impact of perinatal HIV exposure and infection on the growth trajectory of school-aged children in Nigeria. MethodsWithin a prospective cohort, 569 children aged 3-11 years were recruited from pediatric clinics in Nigeria and matched by age and sex based on their exposure or infection status. School-aged children were observed across three time-points at 6-month intervals, during which anthropometric measures, CD4 count, and maternal factors were collected. Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and body-mass-index-for-age (BAZ) were calculated using WHO standards. Longitudinal linear regression analyses using generalized estimating equations (GEE), adjusted for maternal and child covariates, were conducted to compare growth outcomes across groups. ResultsGrowth Z-scores declined until approximately age 8, after which they gradually increased. Across all visits, CLHIV consistently and independently demonstrated lower Z-scores (WAZ ({beta} = -1.04, p <0.001); HAZ ({beta} = -0.67, p <0.001)), followed by CHEU with intermediate but significant impairments (WAZ ({beta} = -0.35, p <0.01); HAZ ({beta} = -0.38, p <0.01)) compared to CHUU. ConclusionStunting remains unacceptably high in CLHIV and CHEU in SSA. The findings suggest a need for immediate paradigm shifts to address persistent growth deficits despite ART and beyond infancy.

BackgroundSustained retention in care supports continuous access to antiretroviral therapy, routine clinical monitoring, and long-term viral suppression. ObjectiveTo compare the effectiveness of interventions for improving retention in care among people living with HIV (PLHIV). DesignSystematic review and network meta-analysis Data sourcesPubMed, Embase, CINAHL, PsycINFO, Web of Science, and the Cochrane Library from 1995 to December 2024. Eligibility criteriaRandomised controlled trials (RCTs) evaluating interventions to improve retention in care, viral load suppression, or quality of life (QoL) among PLHIV, compared with standard of care (SoC) or other interventions. Data extraction and synthesisPairs of reviewers independently screened studies, extracted data, and assessed risk of bias using ROBUST-RCT. We conducted a fixed-effect frequentist network meta-analysis and rated interventions categories relative to SoC based on effect estimates effects and the certainty of evidence.. Dichotomous outcomes were summarized as odds ratios (ORs) with 95% confidence intervals (CIs), and continuous outcomes as mean differences (MDs) with 95% CI. ResultsEighty-four trials enrolling 107 137 PLHIV evaluated 13 intervention categories. For retention in care, five interventions supported by moderate or high certainty evidence proved superior to SoC: multi-month dispensing (OR 2.02, 95% CI 1.32 to 3.09), task shifting (OR 1.94, 95% CI 1.42 to 2.66), differentiated service delivery (OR 1.47, 95% CI 1.22 to 1.76), behavioural counselling (OR 1.36, 95% CI 1.21 to 1.54), and supportive interventions (OR 1.31, 95% CI 1.11 to 1.55). For viral load suppression, two interventions supported by moderate or high certainty evidence proved superior to SoC: task shifting (OR 2.07, 95% CI 1.25 to 3.43) and behavioural counselling (OR 1.34, 95% CI 1.11 to 1.67). Across outcomes, no intervention demonstrated convincing superiority over other active interventions. ConclusionsAmong 13 intervention categories, only a subset provided moderate or high-certainty evidence of superiority to the standard of care, and no superiority to other interventions. Persistent evidence gaps for key populations, diverse settings, and long-term outcomes support the need for context-sensitive and patient-centred interventions. RegistrationPROSPERO CRD42024589177 Strengths and limitations of this study[tpltrtarr] This systematic review followed Cochrane methods and was reported in accordance with PRISMA-NMA guidelines. [tpltrtarr]The network meta-analysis integrated direct and indirect evidence to compare multiple intervention categories within a single framework. [tpltrtarr]Risk of bias and certainty of evidence were assessed using ROBUST-RCT and the GRADE approach for network meta-analysis, respectively. [tpltrtarr]Some networks were sparse, and limited representation of key populations and long-term follow-up constrained the strength and generalisability of inferences.

Background: Pre-exposure prophylaxis (PrEP) is an effective HIV prevention tool, yet uptake and adherence remain low in Kenya despite integration into national HIV prevention plans since 2017. Intimate partner violence (IPV) is a prevalent HIV-related syndemic that presents barriers to PrEP engagement. While IPV's impact on women's PrEP use has been documented, less is known about IPV prevalence among men and its association with PrEP eligibility. This study aimed to determine IPV prevalence and explore correlates among PrEP-eligible men and women in coastal Kenya. Methods: This secondary analysis used data from the "Tambua Mapema Plus" trial conducted at six healthcare facilities in coastal Kenya among HIV-negative participants who were sexually active in the last 6 weeks and PrEP-eligible based on Kenya's Rapid Assessment Screening Tool. IPV was assessed through screening questions covering physical, verbal, and sexual violence experiences. Participants with ongoing IPV were excluded for safety. Among 1,500 intervention participants, 638 (402 women, 236 men) met PrEP eligibility criteria. Modified Poisson regression with robust standard errors was used to identify factors associated with IPV. Results: Overall, 24.1% reported lifetime IPV exposure, with 5.6% reporting past-month IPV. Women experienced higher rates of verbal (14.9% vs 11.0%), physical (15.2% vs 9.7%), and sexual IPV (11.2% vs 6.4%). Participants who had children (adjusted risk ratio [ARR]=2.09, 95%CI 1.32?3.32) or engaged in sex work (ARR=1.81, 95%CI 1.13?2.80) had increased IPV risk. In multivariable analysis, women with children had higher IPV risk (ARR=2.30, 95%CI 1.29?4.24), while men engaging in sex work had elevated risk (ARR=2.37, 95%CI 1.15?4.68). Discussion: IPV prevalence was substantial. Sex work emerged as a risk factor for both sexes, while having children increased risk among women. High IPV prevalence among PrEP-eligible individuals underscores the need for integrated IPV risk assessment in PrEP programs to improve HIV prevention effectiveness in Kenya.

Background: Cervical cancer remains a major public health challenge among women living with HIV (WLWH) in sub-Saharan Africa, where screening coverage remains suboptimal despite opportunities for integration within HIV care programs. Visual inspection with acetic acid (VIA) has been widely used as a low-cost screening approach in resource-limited settings. Methods: This cross-sectional analysis utilized prospectively collected data from Project CN001 at the Coptic Hope Center for Infectious Diseases in Nairobi, Kenya, a CASCADE Clinical Trials Network site. WLWH aged 25-49 years receiving routine HIV care and undergoing VIA screening between March 11, 2025, and January 16, 2026, were included. Data from the REDCap and Kenya's electronic medical record system (KenyaEMR) captured sociodemographic characteristics, HIV clinical factors, VIA results, and cervical transformation zone (TZ) classification. Results: Among 857 WLWH screened with VIA, the median age was 40 years (interquartile ranges [IQR]: 34-45), and 77.2% reported a prior history of cervical cancer screening. VIA positivity was 7.4% (63/857) and was higher in women with TZ1/TZ2 than in those with TZ3. VIA positivity was also associated with higher HIV viral load, shorter time since HIV diagnosis, no cervical screening history, and younger age at screening. The proportion of women classified as TZ3 increased with age, from 39.5% among women aged 25-29 years to 67.7% among those aged 45-49 years, while the proportion classified as TZ1 decreased with increasing age. Conclusion: Integrated screening at this urban U.S. President's Emergency Plan for AIDS Relief (PEPFAR) and CASCADE-supported HIV clinic demonstrates the feasibility of integrated cervical cancer screening programs for WLWH. Age-related TZ3 predominance and VIA limitations for older women highlight the need for refined screening strategies and continued electronic platform utilization for program monitoring to support cervical cancer elimination targets.

Introduction. Empirical evidence linking specific national structural policies to the provision of key HIV services in low- and middle-income settings remains scarce. This study addresses the research gap by quantifying the within-country relationships between six national structural policy indicators and the presence of the HIV prevention service component targeted at sex workers in Southeast Asia. Methods. We constructed a balanced panel dataset covering eight Southeast Asian countries from 2018 to 2025 from the UNAIDS Global AIDS Monitoring (GAM) framework. We used Fixed-Effects (FE) and Random-Effects (RE) models to analyse the relationships, with the FE model selected as the more statistically appropriate estimator. We enhanced robustness by using clustered standard errors and one-period lagged explanatory variables. Results. The primary finding from the FE model indicated a statistically significant and positive contemporaneous association between the existence of legal or administrative barriers to social protection (barriers_spi,t) and the presence of HIV prevention services for sex workers ({beta} = 0.8531; p < 0.001). However, the robustness check revealed a statistically significant negative association between the two when using the lagged barrier variable (barriers_spi,t-1), suggesting a decline in HIV prevention service availability over time ({beta} = -0.3540; p < 0.05). We did not find any other policy variable's coefficient to be statistically significant in the FE models. Conclusions. While the immediate recognition (contemporaneous effect) of structural barriers to access social protection may occur alongside prioritised HIV prevention service provision, the sustained presence of these impediments acts as a long-term constraint that undermines the effectiveness and sustainability of targeted HIV programmes. National HIV programmes must urgently prioritise the removal of structural barriers to ensure long-term service stability for key populations.

Tuberculosis (TB) remains a leading cause of death globally, with early mortality often driven by severe malnutrition and human immuno-deficiency virus (HIV) co-infection. Traditional survival analyses identify risk factors but remain associative, failing to capture the dynamic physiological collapse preceding death. In a novel interdisciplinary adaptation, we applied the Merton jump-diffusion structural framework from quantitative finance to model survival as a state of biological solvency, in which mortality occurs when a stochastic health trajectory crosses a critical failure threshold. We analysed a retrospective cohort of 15,182 TB patients in Cameroon over two decades. Adjusted body mass index (BMI) was conceptualized as a proxy for health capital and modeled using a stochastic process accounting for individual recovery trends, physiological instability, and acute clinical shocks. The study included predominantly young adult males (median age: 33 years) with a median BMI of 20.7 kg/m2. HIV co-infection was present in 35% of patients. The overall mortality rate during the 240 days follow-up period was 7.0%, with 55.1% of deaths occurring within the first 30 days. The model identified a critical failure threshold at BMI 17.329 kg/m2. HIV co-infection emerged as a key driver of metabolic instability, significantly increasing physiological volatility. Statistical validation confirmed that sudden clinical shocks were necessary to explain observed mortality patterns. The resulting Distance-to-Death (DtD) metric slightly outperformed standard associative extended Cox models in predicting survival, achieving a higher discriminative ability in testing set (Harrells C-index: 0.781 vs. 0.772; p = 0.038). Patients stratified into the highest-risk category showed a mortality rate of 16.7%, compared with 1.6% in the most stable group.This study bridges financial engineering and clinical epidemiology, offering a mechanistic understanding of how physiological reserves and metabolic instability determine survival. To support clinical application, we developed an interactive digital triage tool enabling identification of high-risk patients in resource-limited settings. Author summaryTuberculosis remains a major cause of death worldwide, particularly in people with poor nutrition or co-infection with HIV. In this study, we explored a new way to understand why some patients survive while others do not. We adapted a method originally used in finance to track the "health reserves" of patients over time, using body weight and related measures to estimate how close someone is to a critical health threshold. Our approach captures both gradual health decline and sudden medical complications, such as severe infections or rapid deterioration. By applying this method to a large group of patients in Cameroon, we found that a very low body weight is a strong warning sign for impending death and that HIV infection makes health outcomes less predictable. We also created a simple scoring tool that can help doctors identify patients at greatest risk, so that life-saving interventions and closer monitoring can be prioritized. This work bridges mathematical modeling and clinical care, offering a new way to assess patient vulnerability and improve outcomes in resource-limited settings.

IntroductionOn January 20, 2025, the U.S. government froze foreign assistance including for PEPFAR, though a limited waiver for "life-saving" interventions was subsequently granted. PEPFARs 2025 monitoring results, released April 17, 2026, covered only quarter 4 while an earlier inadvertent release included all four quarters. Combining both data sets, we systematically assess facility-level programmatic performance and reporting trends to quantify service disruptions accounting for reporting discrepancies. MethodsWe categorized facilities by reporting continuity across Q1 2024 and Q4 2025 (e.g. continuous, intermittent, dropped, or new) and assessed changes in service delivery by the category of health facility for key HIV treatment, testing, PMTCT, and prevention programming. We additionally analyze changes in employed human resources for health (HRH) reported by PEPFAR. ResultsPEPFAR data included 31,746 facilities and community service sites. 71.3% were classified as continuous reporters, 16.9% intermittent reporters, 2.5% community services, 3.9% dropped in 2025, and 3.1% new in 2025. Total number of people accessing HIV treatment declined modestly by -0.3%, but differed by facility category. Continuous facilities saw a 0.5% increase in people on treatment, while intermittent facilities saw a -1.7% decrease. HIV testing declined -17%. HIV diagnoses declined -13% in continuous facilities, -35% in community services, and -29% in intermittent facilities. PMTCT infant testing and diagnoses declined by -6% and -12% in continuous facilities, respectively, and -60% and -31% in intermittent facilities, respectively. PrEP initiations declined -33%. Total direct service delivery HCWs reduced -62,541 (-24%) ConclusionThese findings reveal substantial disruptions across PEPFAR service areas, with the steepest declines among intermittent and community-based delivery sites, alongside a 24% reduction in direct service delivery healthcare workers. As potentially the final data set PEPFAR will ever release, these findings represent a troubling inflection point. The dismantling of public data systems and accountability structures undermine progress and enable programmatic gaps to develop and go unnoticed that risk allowing HIV resurgence to occur over the coming years.