Objective: Chronic immune activation and microbial translocation may contribute to hepatic fibrosis in people with HIV. We evaluated whether plasma kynurenine-to-tryptophan (KT) ratio and other biomarkers of microbial translocation predict incident fibrosis in women with HIV. Design: Longitudinal cohort study of 709 women with HIV from the Women's Interagency HIV Study with baseline plasma biomarkers and serial vibration-controlled transient elastography. Participants with baseline fibrosis or viral hepatitis were excluded. Outcomes included incident fibrosis, steatotic liver disease (SLD)-associated fibrosis, non-SLD fibrosis, and advanced fibrosis. Methods: Poisson regression with robust standard errors clustered by participant was used to estimate incidence rate ratios (IRRs) for liver outcomes by log-transformed KT ratio, adjusted for demographic, metabolic, and HIV-related covariates. Models included an offset for follow-up time. Analyses were repeated for sCD163, sCD14, and I-FABP. Results: Over a mean follow-up of 42 months, 18.7% developed incident fibrosis, of whom 74% had SLD; 8.3% developed advanced fibrosis. In adjusted models, each log-unit increase in KT ratio was associated with incident fibrosis (IRR 1.46, 95% CI 1.21–1.76) and advanced fibrosis (IRR 1.59, 95% CI 1.27–1.99). KT ratio was associated with non-SLD fibrosis (IRR 1.59, 95% CI 1.31–1.94), but not SLD-associated fibrosis (IRR 1.16, 95% CI 0.94–1.42). Higher sCD163 was associated with all liver outcomes, whereas sCD14 and I-FABP were not. Conclusions: Higher KT ratio independently predicted incident hepatic fibrosis in women with HIV, particularly non-SLD fibrosis, suggesting a steatosis-independent pathway involving microbial translocation and macrophage activation.
Background: Full tryptophan (T) profiling allows determination of T-metabolites from the serotonin, kynurenine (K) and gut-integrity/indole pathways. We assessed T-metabolites, depressive symptoms, cognitive function and sleep measures in persons with and without HIV. Methods: Persons with HIV on ART and lifestyle-similar persons without HIV completed depressive symptoms questionnaire (PHQ-9), cognitive testing ( T -score), actigraphy sleep measures and early morning fasting blood sampling for metabolomic profiling (LC-MS, UK National Phenome Centre). Statistical analysis used Mann–Whitney U tests and Spearman rank correlation. Results: Of 468 individuals (345 with HIV), 81% were male individuals and median age was 58 (IQR 53–63) years. Several metabolites, including K , K / T ratio, citrulline and 5-hydroxyindole-acetic-acid, differed in those with and without HIV. Median (IQR) PHQ-9 scores were 5 (1–10) and 1 (0–3) in those with and without HIV, respectively. In those with HIV, higher PHQ-9 scores were associated with higher K-pathway markers [quinolinic acid ( P = 0.05), K ( P = 0.02) and K / T ratio ( P = 0.02)] but associations were generally weaker in those without HIV. Cognitive testing T -score [with HIV: 50 (44–54.9); without HIV: 52 (48.3–55.8)] was positively associated with higher gut-integrity/indole-markers in those with HIV [citrulline ( P < 0.0001), indole-3-acetic-acid ( P < 0.0001)], but less so in those without HIV. No associations between any actigraphy sleep measures and T-metabolites were observed. Conclusions: K-pathway metabolites (driven by peripheral inflammatory responses) are associated with depressive symptoms and metabolites of gut health associated with cognitive function in those with HIV; these observations were less evident in those without HIV. Further understanding of these mechanisms could assist the development of future therapeutic interventions.
Objective: To evaluate the relevance of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) combined with exercise testing, performed in asymptomatic people with HIV receiving effective antiretroviral therapy (ART), for detecting baseline silent coronary heart disease (SCHD) and predicting incident cardiac events. Design: Retrospective observational study conducted between November 2015 and July 2024 at Saint-Louis Hospital, Paris. Methods: We screened people with HIV with no history of coronary artery disease for SCHD using MPI combined with exercise testing. Patients with abnormal findings underwent coronary angiography. Baseline SCHD was defined as the presence of significant coronary stenosis confirmed by coronary angiography. Incident cardiac events during follow-up included incident SCHD, myocardial infarction, chest pain associated with significant coronary stenosis, and sudden death. Baseline risk factors associated with SCHD and cardiac events were assessed using univariate and multivariate analyses. Results: A total of 475 people with HIV were analyzed, with a median follow-up of 6 years. The median age was 56 years, 87.8% were male, 58.1% were current or ex-smokers, and 29.9% were on statins. The baseline prevalence of SCHD was 2.1% [95% confidence interval (CI): 1.1–4]. During follow-up, the incidence of cardiac events was 1.2 per 100 person-years (95% CI: 0.8–1.7). Only a combined positive MPI and exercise testing was associated with a significantly increased risk of SCHD and cardiac events [adjusted odds ratio (aOR) 4.0; 95% CI: 1.91–8.35; P < 0.001]. Conclusion: SPECT MPI combined with exercise testing can detect SCHD and may help identify people with HIV at increased cardiovascular risk.
Background: Understanding the factors associated with long-term intact HIV-1 proviral dynamics during suppressive ART is critical for developing HIV-1 cure strategies. In this study, we sought to evaluate the association between sex assigned at birth and HIV-1 reservoir dynamics in people with HIV (PWH) on long-term suppressive ART. Methods: Adult participants (17 men; 18 women) of the MACS/WIHS Combined Cohort Study with ≥10 years of suppressive ART and samples collected at 4–5-year intervals were included. We used the intact proviral DNA assay (IPDA) to measure intact and defective HIV-1 proviruses. Soluble inflammatory markers and, in women only, sex hormones were measured. Correlation was evaluated using Spearman's rank correlation test. Results: Among the 35 PWH, median follow-up was 12 years; 16 demonstrated continuous decreases in intact proviruses, while 19 had non-decrease patterns. Female sex and age at viral suppression were associated with a higher proportion of continuous intact HIV-1 DNA decreases, while age at ART initiation and nadir CD4 + cell count were not. By contrast, decrease in total and defective proviruses were not significantly different between the sexes. Higher estradiol levels in female PWH negatively correlated with interleukin 6 (IL-6, rho = −0.53, P = 0.001), and IL-6 negatively correlated with intact proviruses (rho = −0.38, P = 0.01). In male PWH, D-dimer rather than IL-6 negatively associated with intact proviruses (rho = −0.34, P = 0.02). These soluble markers and hormones were not associated with reservoir decay patterns. Conclusions: Among PWH with decade-long suppressive ART, less than half had sustained decline in intact proviral DNA. Female PWH more often exhibited continuous decline in intact HIV-1 DNA.
Objective: To evaluate adherence to hepatitis B virus (HBV) management recommendations among people with HIV (PWH) and chronic HBV infection. Design: A multicenter cross-sectional study. Methods: We conducted a cross-sectional study in 42 centers in Spain and Germany between June 2024 and March 2025. Chronic HBV infection was defined as at least two positive hepatitis B surface antigen tests obtained more than 6 months apart. Adherence to 2023 European AIDS Clinical Society recommendations regarding anti-HBV treatment, liver enzyme monitoring, HBV-DNA testing, antihepatitis D virus (HDV) screening, and HDV-RNA confirmation was assessed. Hepatocellular carcinoma surveillance was evaluated separately and has been reported elsewhere. Results: A total of 1235 PWH with chronic HBV infection were included. The median age was 56 years, 84% were men, and 36% were born outside Europe. Overall, 88% had HIV-RNA less than 50 copies/ml, and the median CD4 + cell count was 623 cells/μl. Among participants with available HBV-DNA result, 87% had undetectable HBV-DNA. Guideline-recommended anti-HBV treatment was documented in 88% of individuals. During the previous 12 months, liver enzyme monitoring was performed in 94% and HBV-DNA testing in 71%. Overall, 81% had ever undergone anti-HDV testing and, among anti-HDV-positive individuals, 66% had undergone HDV-RNA testing. Conclusion: Although adherence to several components of HBV care was high, gaps remain in the implementation of current recommendations for PWH, particularly in HBV-DNA monitoring and HDV evaluation. Better integration of these measures into routine HIV care may improve long-term prevention of liver-related complications.
