AIDS最新文献

The breadth of the overdose crisis is underestimated because of a lack of quantifying nonfatal overdoses. We estimate the proportion of nonfatal overdoses among all people with HIV (PWH) in British Columbia, Canada, and the prevalence of fatal overdoses among people who had a nonfatal overdose, stratified by sex. A small proportion of PWH who experienced a nonfatal overdose subsequently died of a fatal overdose, signaling opportunities for crucial interventions and treatment to prevent overdose death.

Objective: The ability of HIV-1 Nef to counteract the host restriction factor SERINC5 and enhance virion infectivity has been well established. However, the impact of long-term within-host Nef evolution on this antagonistic capability remains unclear.

Design: Analysis of longitudinal activity of Nef in antagonizing SERINC5.

Methods: We investigated the downregulation activity of Nef against SERINC5 at different stages of infection by analyzing the cognate transmitted/founder, set point, and/or chronic Nef isolates from a cohort of 19 people with either subtype B or C HIV-1.

Results: The Nef isolates from different stages exhibited varying abilities to antagonize SERINC5. Long-term evolution resulted in mutations accumulated in Nef and a decline of Nef-mediated SERINC5 downregulation function in subtype B, but not in subtype C viruses, leading to a rapid reduction in viral load from peak viremia. Furthermore, we identified four polymorphisms of both subtype B and C Nef that are associated with variations in the SERINC5 antagonistic function and viral infectivity. HIV-1 NL4-3 variants encoding Nef E63G, A83G, R105K, or D108E mutants exhibited reduced replication capacity through a SERINC5-dependent mechanism. However, among different subjects, only a small part of naturally occurring mutations at these sites were selected by host T-cell responses, suggesting a limited impact of host T-cell responses on influencing Nef's ability to antagonize SERINC5.

Conclusion: These results highlight the potential contribution of functional variation in Nef to differences in HIV-1 pathogenesis and provide significant implications for understanding the evolutionary interaction between Nef and SERINC5 in vivo .

Objectives: The aim was to investigate whether switching from efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/F/TDF) to bictegravir/emtricitabine/tenofovir alafenamide (BIC/F/TAF) may improve neuropsychiatric symptoms and neurocognition.

Design: Pilot, single-arm, prospective study of persons with HIV (PWH) on the efficacy and safety of switching from EFV/F/TDF to BIC/F/TAF.

Methods: Participants underwent neuropsychological assessment (NPA) at switch (T0) and after 48 weeks (T1). NPA was carried out through a standardized battery of 12 tests. Neurocognitive impairment (NCI) was defined by a score of at least 1 standard deviation (SD) below the normal mean on at least two tests or ≥2 SD below on one test. Individual z scores were determined, NPZ-12 was calculated as the average of 12 test z scores and change of NPZ-12 was the outcome. HIV-associated neurocognitive disorder (HAND) was classified by Frascati's criteria. Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI-II), and Pittsburgh Sleep Quality Index (PSQI) were administered. Paired-Wilcoxon and McNemar tests were used for comparisons, and logistic regression for associations with NCI changes.

Results: Out of 126 participants, BAI, BDI-II, and PSQI questionnaires revealed an improvement at T1. NPA revealed NCI in 40.5% of persons at T0 and 42.1% at T1 ( P  = 0.746). Specifically, at T0, among participants with NCI, 35% improved; among those without, 26% worsened at T1; NPZ-12 score worsened at T1. 5.6% of ANI was observed at T0 and 7.9% at T1. No factor associated with these changes was found.

Conclusion: Our results suggest switching from EFV/F/TDF to B/F/TAF significantly improves psychiatric symptoms and sleep quality. Neurocognitive performance remained stable, although a decline in NPZ-12 and in specific domains was observed.

Objective: Elevated blood pressure (BP), even at prehypertensive levels, increases cardiovascular disease risk among people with HIV (PWH); yet international guidelines in low-income countries recommend treatment initiation at BP at least 140/90 mmHg. We determined the efficacy, feasibility, and acceptability of treating prehypertension in PWH in Haiti.

Design: An unblinded randomized clinical trial (enrolled April 2021-March 2022) with 12-month follow-up.

Setting: GHESKIO Centres, Port-au-Prince, Haiti.

Participants: Two hundred fifty adults with HIV with prehypertension (SBP 120-138 or DBP 80-89) not on medication, aged 18-65 years, virally suppressed, and without pregnancy, diabetes, or kidney disease.

Intervention: Participants were randomized to treatment (amlodipine 5 mg) or control (no amlodipine unless two BP ≥140/90 mmHg).

Main outcome measure: Primary outcome was mean change in SBP between intervention versus control groups from enrollment to 12 months.

Results: Among 250 adults, median age was 49 years, 40.8% were women. Baseline median BP was 129/78 mmHg intervention versus 128/77 mmHg control. After 12 months, the difference in mean change between study groups for SBP was -5.9 mmHg [95% confidence interval (95% CI) -8.8 to -3.0] and for DBP was -5.5 mmHg (95% CI -7.9 to -3.2). At 12 months, 5.6% intervention and 23.0% control participants developed incident hypertension (hazard ratio 0.18; 95% CI 0.07-0.47). There were no differences in viral load suppression at 12 months or drug-related serious adverse events. Intervention acceptability was high among providers and participants in qualitative interviews.

Conclusion: In PWH in a resource-poor setting, prehypertension treatment was feasible, acceptable, and effective in reducing mean SBP and incident hypertension.

Registration: Clinicaltrials.gov NCT04692467.

Objective: Falls are a significant public health concern, particularly among older adults and people with HIV (PWH). This study examines the association between alcohol consumption and falls in PWH.

Methods: The PROSPER-HIV study recruited PWH from four US sites. Participants were categorized based on Alcohol Use Disorders Identification Test Consumption (AUDIT-C) scores: none, nonhazardous, and hazardous drinking. Data collection included demographics, medical history [i.e. comorbidities, treated hypertension, estimated glomerular filtration rate (eGFR)], alcohol consumption using AUDIT-C, daily alcohol recall in grams, and self-reported falls over the previous year. Physical performance was measured using the Short Performance Physical Battery (SPPB). Statistical analyses included Pearson's correlation and Poisson regression models to estimate fall prevalence ratios, adjusting for confounders (SPPB, comorbidities, treated hypertension, and eGFR).

Results: The study included 315 PWH, aged 52 ± 12 years, with 78% male participants. Thirty-three percentage were classified as nondrinking, 50% nonhazardous, and 17% hazardous drinking. Poisson regression showed a significantly higher risk of falls [prevalence ratio: 2.12, 95% confidence interval (CI) 1.11-4.03] and recurrent falls (prevalence ratio 3.54, 95% CI 1.21-10.3) among hazardous drinking compared with nonhazardous drinking, even after adjusting for confounders. The prevalence ratios for falls per daily intake in grams was not statistically significant.

Conclusion: There is a significant association between hazardous alcohol consumption and increased fall risk in PWH using AUDIT-C but not when accessing recall of alcohol consumption in grams.

Objective: The aim of this study was to identify the prevalence of emergent integrase drug resistance mutations (INSTI-DRMs) in international referrals to a perinatal virtual clinic (PVC).

Design: A retrospective cohort study.

Setting: Monthly multidisciplinary PVC reviewing complex case management for children and adolescents with perinatally acquired HIV (CAWHIV).

Participants: One hundred fourteen cases referred for virological failure between October 2018 and January 2024.

Main outcome measures: Data collected included age, sex, weight, country of residence, antiretroviral therapy (ART) history, HIV viral load, CD4 + cell count, and comorbidities. Resistance mutations were interpreted using the Stanford HIV Drug Resistance database with emergent major INSTI-DRMs described.

Results: Of 114 referrals, 103 (90%) had resistance sequences available. Prior INSTI exposure was documented in 61/103 (59%) with 19/61 (31%) having INSTI-DRMs. For these 19, median (IQR) age was 11 years (6-14), weight 25 kg (17-50), CD4 + cell count 485 cells/μl (153-805), and viral load 84 000 copies/ml (2380-137 000). Twelve of 19 (65%) were from low/middle-income countries (LMIC), 6/19 (32%) had current AIDS diagnoses with 14/19 (74%) referred from 2022 onwards. There were a median three prior regimens with 13/19 (68%) having at least 3 class resistance. Two developed INSTI-DRMs on first-line dolutegravir (DTG)-based ART, 17 on second+ line therapy. PVC recommendations were for tenofovir+ lamivudine/emtricitabine (six split adult tablets) with boosted darunavir [19; six twice daily (b.i.d.)], with b.i.d. DTG (6), plus fostemsavir (1) and ibalizumab (1).

Conclusion: Although uncommon, INSTI resistance is emerging, mainly in highly treatment experienced CAWHIV from LMIC, highlighting the global need for access to boosted protease inhibitors and novel classes, including formulations for children less than 35 kg.

Objective: People with HIV (PWH) face a heightened risk of cardiovascular diseases, partly because of increased high blood pressure risk. This study assessed high blood pressure burden (i.e. incidence and prevalence) among PWH in Kenya over time.

Design: Longitudinal, open cohort study.

Methods: We estimated the incidence and prevalence of high blood pressure in a large sample of Kenyans with HIV from the Coptic Hope Center using electronic medical records from 2004 to 2023. We defined incident high blood pressure as first visit after baseline at which each patient had a SBP at least 140 mmHg and/or a DBP at least 90 mmHg.

Results: Our sample included 38 709 PWH seeking care at Coptic Hope Center clinics in Kenya (2004-2023). Nearly 40% of patients had high blood pressure at first visit. Among the 60% of patients initially normotensive, almost 40% developed high blood pressure within 20 years. The yearly prevalence of high blood pressure ranged from 8 to 58%. Average SBP was higher among patients who had their first visit from 2019 to 2023 compared with those visiting in the early 2000s and 2010s.

Conclusion: Our findings reveal a high and rising burden of high blood pressure among PWH in a large, faith-based health system in Kenya. This underscores the need for stronger integration of care for individuals with concurrent HIV, high blood pressure, and other noncommunicable diseases (NCDs). Current systems are insufficient for achieving blood pressure control among PWH. Further research and funding for efforts to address HIV and NCD care in Kenya are warranted.