AIDS最新文献

Objectives: To assess whether bipolar disorders are associated with the risk of HIV infection and whether the risk of bipolar disorders is increased among people with HIV (PWH) and their siblings.

Design: Nationwide, population-based, combined matched nested case-control and cohort study of PWH of Danish origin (1995-2021), a comparison cohort from the background population, matched on date of birth and sex, and sibling cohorts.

Methods: Conditional logistic regression and Cox regression was used to calculate adjusted odds ratios (aORs) for HIV infection and hazard ratios (HRs) among PWH for bipolar disorder and receipt of lithium.

Results: We included 5322 PWH and 53,220 comparison cohort members. In the case-control study, bipolar disorder was associated with an increased risk of HIV infection (aOR: 1.9, 95% confidence interval (CI): 1.2-3.0), especially when injection drug use was the route of infection (aOR: 7.6, 95% CI: 2.0-28.9). In the cohort study, we observed an increased risk of bipolar disorders among PWH, especially in the first 2 years of observation (HR: 4.2, 95% CI: 2.4-7.4), whereas the risk of receipt of lithium was lower and the CI crossed 1. The 20-year risk of bipolar disorders for PWH was approximately 1%. Siblings of PWH also had an increased risk of bipolar disorder, but not to the same degree as PWH and not of receipt of lithium.

Conclusions: Bipolar disorders are associated with the risk of HIV infection, and PWH have increased risk of bipolar disorder and receipt of lithium beyond what familial factors could explain.

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.

Objectives: The aim was to investigate whether switching from EFV/F/TDF to B/F/TAF may improve neuropsychiatrc 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 B/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 ≥1 standard deviation (SD) below the normal mean on at least 2 tests or ≥2 SD below on 1 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.

Conclusions: 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.

Background: Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared to the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH.

Methods: The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010-2018. Frailty was measured with a validated PRO phenotype, scored 0-4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score.

Results: Among 273 PWH, most were male (91%), average age at baseline was 45, 42% were non-Hispanic White while 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score (95%CI:0.12-0.39). Higher sTNFR1 (0.35 [0.13-0.56]), sCD14 (0.21 [0.11-0.31]), and suPAR (0.24 [0.11-0.36]) levels were also associated with higher frailty scores over follow-up.

Conclusions: Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.

Objective: We aimed to synthesize clinical and economic outcomes of rapid start versus non-rapid antiretroviral therapy (ART) in people with HIV (PWH) in real-world settings.

Methods: A search was conducted in PubMed, Embase, Web of Science, and ProQuest from January 2017 to January 2023, supplementing a previous search by Ford et.al, 2018. Observational studies investigating clinical or economic outcomes of rapid start ART versus non-rapid ART in PWH were included. Clinical outcomes were mortality, loss-to-follow-up (LTFU), and viral suppression. Economic outcomes were Incremental cost-effectiveness ratio (ICER) values and per patient per month (PPPM) costs. Meta-analyses using random-effects models were performed for clinical outcomes, while qualitative syntheses were conducted for economic outcomes. The quality of clinical and economic studies was assessed.

Results: Sixty-two studies were included. The pooled adjusted risk ratio (aRR) for mortality demonstrated a significant reduction in risk of mortality among participants who received rapid start ART compared to non-rapid ART (0.80, 95%CI, 0.65-0.98). For LTFU at 6 and 12 months, the pooled aRR showed increased LTFU for rapid start ART (1.33, 95%CI, 1.15-1.55 and 1.18, 95%CI, 0.74-1.89 respectively). All cost-effectiveness studies reported cost-saving or cost-effective findings. The PPPM costs of rapid start ART across the first 36 months of treatment were consistently lower than non-rapid ART.

Conclusions: Rapid ART is associated with reduced mortality and is cost-effective compared to non-rapid ART in real-world settings. Clinicians and policymakers should consider these findings to facilitate rapid start of ART in PWH. Further research on LTFU in PWH is needed.

Objectives: Worldwide, adult men experience an excess burden of tuberculosis (TB) disease compared to women, but few studies have examined sex differences in TB among people with HIV. In this study, we aimed to investigate sex differences in TB infection and disease among people with HIV in Rio de Janeiro, Brazil.

Design: Analysis of data from a randomized controlled trial and retrospective cohort study.

Methods: We analyzed data from two studies conducted between 2005 and 2017. The THRio Study (2005-2012) evaluated increasing tuberculin skin testing (TST) and TB preventive therapy (TPT) and UnivART (2010-2017) was a virtual cohort study of people with HIV and TB with data from four national electronic registries.

Results: Among 4,606 people with HIV in THRio, 2,992 (65.0%) had a TST placed and read, of whom 312/1,865 (17%) males and 203/1,127 (18%) females (p = 0.37) had prevalent TB infection. TB disease incidence was higher among males compared to females overall (IRR 1.33, 95% CI 1.04-1.69), among males compared to females who did not receive TPT (IRR 1.30, 95% CI 1.01-1.67), and among males compared to females on ART (IRR 1.64, 95% CI 1.17-2.29). Among 54,957 people with HIV in UnivART, TB disease incidence rates were higher among males than females overall (IRR 1.28, 95% CI 1.18-1.39), among males compared to females on ART (IRR 1.58, 95% CI 1.40-1.77), and among males compared to females not on ART (IRR 1.11, 95% CI 0.99-1.25).

Conclusions: In this medium TB and HIV burden setting, TB disease incidence was higher among males than females with HIV, despite similar prevalence of TB infection.

Objective: The study aimed to assess the impact of smoking exposure on major clinical events (MCE) in a real-life setting of people living with HIV (PWH).

Design: Observational longitudinal multicentre cohort study from Italy.

Methods: Consecutive 983 PWH were enrolled in "STOP Smoking in HIV people" (STOPSHIV) projects and followed from July 2014 until September 2023. The observed MCE defined as cardiovascular (CV) events, neoplastic diseases or death for any reason was assessed according smoking status and related variables (number of cigarettes smoked daily, pack-years, Fagerström test) in participants. The association between exposure variables and the event was evaluated using the Cox proportional hazard model (hazard ratios, HR, and 95% CI).

Results: Over 6997.6 person-years of follow-up (PYFU), we found a total of 49 CV events, 61 neoplastic events, and 47 deaths. The overall incidence rate of MCE was 17.6 /1000 PYFU (95% confidence interval 14.7-21.0). All-cause death rate was 6.7 (95% CI 5.0-8.9)/1000 PYFU. In a multivariate analysis, older age (HR 1.07, CI 1.05-1.09), high Fagerström Test for Nicotine Dependence (HR 1.09, CI 1.03-1.15), a low nadir CD4 <200 cells/mm3 (HR 1.63, CI 1.10-1.41), history of previous neoplasm (HR 2.41; CI 1.34-4.43) and intravenous drug use as risk factor for HIV infection (HR 2.36; CI 1.52-3.68) were independent predictors of any MCE.

Conclusions: Non-AIDS clinical conditions are the most observed clinical events in PWH from Italy. Smoking exposure significantly increases the risk of MCE in PWH and a high Fagerström Test for Nicotine Dependence is a predictor of MCE.

Objective: Bictegravir is increasingly prescribed as a co-formulated tablet with tenofovir alafenamide and emtricitabine to pregnant persons with HIV (PWH) despite limited pregnancy and birth outcome data. We sought to provide birth outcome data following exposure to bictegravir during pregnancy.

Design: We conducted a descriptive analysis of infants born to pregnant PWH 18-45 years of age enrolled in at least one Pediatric HIV/AIDS Cohort Study (PHACS)-affiliated study who received bictegravir for ≥7 days during pregnancy and completed follow-up through delivery.

Methods: The outcomes of interest were gestational age at birth, preterm birth (<37 weeks' gestation), gestational-age adjusted birth weight (BWZ) and length (BLZ) z-scores, small for gestational age (SGA, birthweight <10th percentile), congenital anomalies, neonatal deaths in the first 28 days of life, and infant HIV status.

Results: A total of 177 infants born to 170 unique PWH were exposed to bictegravir for ≥7 days during gestation; 55% were exposed to bictegravir from the time of conception. Median gestational age at birth was 38.1 weeks. The prevalence of preterm birth was 15.8% and SGA was 9.3%. Mean BWZ and BLZ were -0.48 and 0.03. No neonatal deaths or perinatal HIV transmissions were reported. Among 126 infants exposed to first-trimester bictegravir, 7 (5.6%) had major congenital anomalies with no specific pattern suggestive of a syndrome.

Conclusions: These findings provide preliminary data without significant safety concerns for fetal bictegravir exposure in this United States cohort. Comparative data and continued surveillance of outcomes among infants exposed to bictegravir during gestation are warranted.

Background: People living with HIV (PLHIV) are at increased risk of tuberculosis (TB). New TB vaccines may help reduce this burden. New TB vaccine candidates are safe and immunogenic in PLHIV.There is currently limited data on vaccine efficacy in this population.

Methods: Using mathematical modelling we explored the potential impact of a novel TB vaccine on TB burden in PLHIV in South Africa between 2030-2050. We compared the impact of a vaccine delivered irrespective of HIV status to vaccination of either PLHIV or people without HIV. We explored the impact of reduced vaccine efficacy and duration of protection in PLHIV relative to people without HIV on our model predictions.

Results: Vaccination irrespective of HIV status, with a vaccine with equal efficacy and duration in PLHIV, could avert up to 1.01 (95% range: 0.96-1.22) million TB cases in PLHIV. Restricting vaccination to PLHIV or people without HIV would achieve 65% (60-70) and 48% (46-53) of the total impact respectively. These results are strongly dependent on the assumed efficacy and duration of protection in PLHIV. Further information on these characteristics is important to identify the most efficient use of new vaccines to reduce TB burden in PLHIV.

Conclusions: Our results suggest that new vaccines could play an important role in reducing the TB burden in PLHIV. Vaccines targeted at people without HIV individuals could provide significant indirect benefit to PLHIV, but vaccines which are safe and effective in PLHIV will be critical to maximizing the impact in this population.

Objectives: Virally-suppressed people with HIV (VS-PWH) show heterogeneity in patterns of cognitive dysfunction. To better understand the relationship between the neuroimmune response and cognition, we used positron emission tomography (PET) to image the translocator protein 18 kDa (TSPO). The study examined HIV-serostatus differences in TSPO as well as associations between regional TSPO and select cognitive processes defined using the Research Domain Criteria (RDoC) framework.

Design: Cross-sectional investigation in VS-PWH (n = 25) versus HIV-uninfected individuals (n = 18) of cognitive control and declarative memory, as well as [11C]DPA-713 PET measures of TSPO within cognitive control and declarative memory regions of interest.

Methods: Group differences in [11C]DPA-713 binding (VT) in cognitive control or declarative memory regions were examined using linear mixed models. Tests of associations between factor-derived cognitive system measures and PET measures were performed, controlling for TSPO genotype.

Results: There were no group differences in any of the four factor-derived cognitive system measures. VS-PWH had higher log [11C]DPA-713 VT across cognitive control regions(unstandardized beta coefficient reflecting mean difference [B] = 0.23, SE = 0.11, 95% confidence interval [CI] 0.01, 0.45, P = 0.04) and declarative memory regions (B = 0.24, SE = 0.11, 95%CI 0.02, 0.45, P = 0.03). Higher log [11C]DPA-713 VT in cognitive control regions related to poorer cognitive control in each group, and to worse self-reported cognitive performance in VS-PWH. Log [11C]DPA-713 VT in each declarative memory region did not associate with measured declarative memory.

Conclusions: A localized neuroimmune response marked by high TSPO in brain regions that subserve cognitive control may contribute to poorer cognitive control in VS-PWH.