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Objective: Perinatal exposure to human immunodeficiency virus (HIV) may disrupt typical neurodevelopment, even without infection. Hemispheric lateralization is a key hallmark of this progress, but it remains poorly characterized in this context. This study investigated gray matter (GM) asymmetry in perinatally HIV-exposed adolescents, both infected and uninfected.

Design: Observational cross-sectional study comparing GM volume and asymmetry across three matched adolescent groups.

Methods: Adolescents aged 11-17 years were recruited: adolescents living with HIV (ALHIV, n = 35), HIV-exposed uninfected (HEU, n = 70), and typically developing controls (TD, n = 30). All participants underwent high-resolution 3D T1-weighted MRI. GM volume and asymmetry index (AI) were quantified using voxel-wise analyses, with validation based on homotopic parcellation. Group differences were tested using one-way ANOVA with correction for multiple comparisons.

Results: Significant group effects in GM volume were observed across sensorimotor, visual, frontal, limbic, and cerebellar regions. Both ALHIV and HEU differed from TD across widespread regions, whereas differences between ALHIV and HEU were more spatially restricted (precentral gyrus, calcarine sulcus and superior frontal gyrus). For GM asymmetry, ANOVA revealed differences in the amygdala, insula, orbitofrontal cortex, and thalamus. Both ALHIV and HEU showed notable differences from TD, while differences between ALHIV and HEU were confined to specific thalamic subregions. Regions of interest (ROI)-wise and meta-analytic validation supported these voxel-wise findings.

Conclusions: Perinatal HIV exposure is associated with atypical GM asymmetry and structural organization in adolescence. Both ALHIV and HEU exhibit deviations from TD peers, with infection status contributing additional localized alterations.

Objective: Patient-reported outcomes (PROs) provide important information to improve healthcare and facilitate research but can be difficult to implement in busy care settings.

Design: We integrated PRO collection into HIV care (2008-2024) with results summarized for providers to improve clinical care.

Methods: PWH presenting for HIV care at nine clinics across the US in the CFAR Network of Integrated Clinical Systems (CNICS) were asked to complete a touch-screen-based PRO assessment at routine clinic visits using a web-based application.

Results: 21,725 PWH completed the CNICS clinical PRO assessment 132,240 times (mean 6.1 assessments per PWH). Mean age at initial assessment was 43.8 years, 24.9% screened in for depression, 35.5% reported heavy episodic (binge) drinking, 38.9% smoking, 10.9% methamphetamine use, 11.7% recent intimate partner violence, and 8.4% reported unstable housing in the prior 30 days.

Discussion: We implemented a PRO assessment into HIV care at nine geographically dispersed clinics. PRO responses in domains known to drive adverse outcomes such as substance use were identified as were situational concerns such as unstable housing. This study demonstrated that use of a well-designed PRO platform can address many of the barriers of paper and interview-based collection and be sustainable over time even as clinic flow and content priorities evolve. It demonstrated that PROs done for clinical care are useful to address clinically relevant research questions and institutional needs. Finally, this study demonstrated the feasibility of wide-spread implementation of a clinical PRO assessment into busy HIV clinical care settings with >130,000 assessments completed to date.

Objective: To assess changes of cardiovascular risk scores and metabolic scores after switching to DOR/3TC/TDF (DOR group), DTG/3TC (DTG group) or BIC/FTC/TAF (BIC group).

Methods: We analyzed data from 1069 virologically-suppressed people with HIV (PWH), collecting clinical history and laboratory parameters at baseline (date of switch) and 48 weeks of follow-up. In eligible PWH we calculated Body Mass Index (BMI), SCORE-2 for cardiovascular risk assessment and the Metabolic Score for Insulin Resistance (METS-IR) at both timepoints and performed linear mixed model for repeated measures to measure changes in parameters, while using linear regression analyses to search for predictors of change.

Results: After 48 weeks, we observed significant changes in median SCORE-2 in all groups: there were increases of +0.12 in the DTG group (p = 0.021) and +0.30 in the BIC group (<0.001), while we observed a decrease of -0.35 in the DOR group (p < 0.001). In our regression analyses, taking DOR/3TC/TDF was a predictor of reduction of SCORE-2 compared with both DTG (p < 0.001) and BIC (p < 0.001).Regarding BMI, after 48 weeks we observed a median increase of +0.2 in BIC (p < 0.001), no changes in the DTG group and a median decrease of -0.04 in the DOR group (p < 0.001).Regarding METS-IR, after 48 weeks we observed a significant decrease in the DOR group (-0.9, p = 0.024), while there were no significant changes with DTG and an increase of +0.3 with BIC (p = 0.013).

Conclusion: We found that switching to DOR/3TC/TDF was associated with more favorable changes in SCORE-2 and METS-IR compared to DTG/3TC and BIC/FTC/TAF.

Objective: With a rapidly aging population living with HIV that may face a double-hit of neuroHIV and Alzheimer's disease, the objective of this meta-analysis was to evaluate the impact of ε4 on cognitive performance in adults with HIV.

Design: The primary literature search was conducted with PubMed and other databases on studies published between 1997 and 2025. Searches were conducted from inception until June 2025.

Methods: Out of 289 initial studies, 17 were identified for inclusion meeting pre-defined criteria. Data extraction was performed by two independent observers and followed established guidelines (PRISMA).

Results: Pooled data included a total of 2610 adults with HIV, including 765 ε4 carriers (age 45.3 ± 8.1 years, 62.1% male) and 1845 non-carriers (age 44.7 ± 9.2, 67.5% male). There was no significant difference between ε4 carriers and non-carriers in diagnosis of neurocognitive impairment (OR = 1.10, 95% CI 0.8 to 1.5 p = .563), nor in performance of any of the examined cognitive domains (Hedges gs<0.2, ps > 0.17). Meta-regression analysis suggested that less education was associated with increased risk of neurocognitive impairment in carriers (p = .0143).

Conclusions: After controlling for the potential bias from "overrepresented" cohorts that appeared in multiple publications, this meta-analysis found no significant effects of ε4 on neurocognitive performance or impairment in adults with HIV, despite a weak and non-significant trend of low performance in memory and executive function in ε4 carriers. Factors such as a relatively young age may contribute to the null findings. Future studies with relatively older cohorts and more sensitive/interdisciplinary approaches are needed.

Objective: To describe the distribution of HIV-1 variants in population-based national surveys conducted in sub-Saharan African countries between 2015 and 2022.

Design: Multicountry analysis.

Methods: Sixteen population-based national surveys, conducted between 2015 and 2022, were analyzed. Survey participants were eligible if HIV genotyping was successful. In most countries, people with HIV (PWH) with a recent infection, children with HIV younger than 18 months, and a country-specific selection of PWH with a nonrecent infection were included. In Nigeria and South Africa, PWH were eligible when viral load >200 or >1000 RNA copies/ml, respectively. HIV-1 variants were identified using the REGA HIV-1 & 2 Automated Subtyping Tool version 3.0. The estimated distributions of HIV-1 variants for each survey were calculated as the percentage distribution.

Results: The sample size varied between 42 and 1434 PWH per country survey. Country distributions showed great variation, with a majority of CRF02_AG in Cameroon, Côte d'Ivoire and Nigeria; a majority of subtype A in Kenya, Rwanda, and Uganda; near equal proportions of subtype C (39%) and subtype A (37%) in Tanzania, and dominance of subtype C (>90%) in Ethiopia, Eswatini, Lesotho, Malawi, Namibia, South Africa, Zambia, and Zimbabwe. Recombinant viruses were mostly found in countries in West-Africa.

Conclusions: The distribution of HIV-1 variants by country and region in sub-Saharan Africa showed important variation. HIV-1 diversity may need to be accounted for during the development of HIV diagnostic and viral load tests, vaccines, other prevention interventions, and treatment.

Objective: To assess the impact of AGT103-T, an autologous CD4+ T-cell and gene therapy, on HIV proviral DNA reservoir.

Design: Intact proviral DNA is quantified using the intact proviral DNA assay (IPDA). Here, IPDA was modified and analytically qualified for use in people living with HIV (PLWH) treated with lentiviral-based therapies and applied to samples from six participants who received AGT103-T.

Methods: Standard IPDA targets overlap with sequences present in lentiviral vectors, including the AGT103-T therapeutic vector, preventing accurate quantification. We developed a modified IPDA that avoids vector interference while preserving detection of intact HIV proviruses by targeting HIV Gag and Nef regions. The assay was qualified for specificity, linearity, and reproducibility using plasmid standards and human DNA. Enriched CD4+ T cells from peripheral blood collected pre-treatment, post-treatment, and during analytical treatment interruption in a Phase 1 trial (NCT04561258; NCT05540964) were analyzed.

Results: Intact proviral DNA declined in all six participants following AGT103-T treatment and reached below the assay's lower limit of detection by the end of follow-up. In contrast, defective proviral DNA showed variable changes without a consistent decline.

Conclusions: AGT103-T treatment was associated with a reduction in intact HIV proviral DNA within circulating CD4+ T cells. These findings extend prior reports describing positive immune and virologic outcomes in AGT103-T-treated participants during analytical treatment interruption. The modified intact proviral DNA assay enables accurate measurement of the intact HIV reservoir in the context of lentiviral gene therapy and supports continued clinical evaluation of AGT103-T.

Objectives: To examine the association between exposure to antiretroviral therapy (ART) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in a Danish cohort of people living with human immunodeficiency virus (PWH).

Design: Cross-sectional observational study.

Methods: MASLD was defined as a transient elastography-derived Continuous Attenuation Parameter ≥275 dB/m and ≥1 cardiometabolic risk factor. We analyzed associations between MASLD and exposure to ARTs using multivariable logistic regression, adjusted for age, sex, BMI, HIV diagnosis duration, diabetes, and comorbidity burden. ART use was categorized as none, past, or current. Non-linearity of cumulative exposure was assessed by comparing linear versus quadratic terms via a likelihood ratio test to select the final model.

Results: The prevalence of MASLD was 29.5% in 397 participants. Current bictegravir use was associated with higher odds of MASLD (aOR = 2.41; 95%CI: 1.15-5.04), while current use of nevirapine was associated with lower odds of MASLD (aOR = 0.26; 95%CI: 0.08-0.85). Similarly, cumulative exposure to bictegravir, tenofovir alafenamide (TAF), and ritonavir or cobicistat boosted atazanavir was associated with MASLD. The relationship was inversely U-shaped for bictegravir and TAF with increasing predicted probability of MASLD up to 2.1 years of cumulative bictegravir exposure, for TAF up to 2.7 years of cumulative exposure. Cumulative exposure to boosted atazanavir was associated with higher odds of MASLD (aOR = 1.09; 95%CI: 1.01-1.18).

Conclusion: Our findings suggest that commonly used antiretrovirals may contribute to the development of MASLD. Prospective studies examining the possible causal effects of these therapies on MASLD development and progression are warranted.

Objective: To assess the effectiveness of once- and twice-daily ritonavir-boosted darunavir (DRV/r)-containing regimens for treating HIV in pregnancy to inform the 2025 World Health Organization antiretroviral treatment guidelines update.

Design: Analysis of pooled data from two observational study networks with sites in Romania, Switzerland and the United Kingdom.

Methods: Pregnancies resulting in a live birth or stillbirth in women receiving 800/100 mg DRV/r once-daily or 600/100 mg twice-daily during pregnancy were included. The primary outcome was viral suppression (<50 copies/mL) near delivery (from 28 days prior to 7 days after delivery).

Results: Among 162 women on once-daily DRV/r, 95% were virally suppressed near delivery, with no difference between those on DRV/r from conception (95%, 113/119) and those who started on or switched to DRV/r during pregnancy (95%, 41/43). Among 27 women on twice-daily DRV/r, 78% were virally suppressed near delivery. Most women remained on the same DRV/r regimen until delivery, and there were no vertical transmissions. Darunavir drug concentrations for the limited number of pregnancies with data available fell within the expected ranges.

Conclusions: This analysis provides some reassurance that once-daily DRV/r can be used successfully in pregnancy. However, given the possibility of reduced drug levels in pregnancy with once-daily dosing, viral load monitoring during pregnancy remains essential. Surveillance of pregnancies in women receiving once-daily DRV/r is needed to further support the use of this dosing during pregnancy.

Objectives: We aimed to estimate the burden of neonatal mortality attributable to preterm births associated with maternal HIV infection in sub-Saharan Africa in 1990-2020.

Design: Modelling study.

Methods: Estimates of the excess risk of preterm birth among pregnant women living with HIV (WLHIV) in sub-Saharan Africa in 1990-2020 were obtained from a systematic review and meta-analysis. Data on preterm birth, neonatal mortality, and deaths <1 year directly caused by HIV/AIDS were obtained from the Global Burden of Disease Study 2021. Information on antiretroviral treatment received by WLHIV in sub-Saharan Africa in 1990-2020 were obtained from UNAIDS. These data were used to estimate neonatal mortality due to HIV-attributable preterm birth in countries in sub-Saharan Africa in 1990-2020.

Results: In 1990-2020, there were an estimated 85,288 (95% confidence interval 53,147-136,921) neonatal deaths due to HIV-attributable preterm births in sub-Saharan Africa. The number of neonatal deaths due to HIV-attributable preterm births in sub-Saharan Africa increased during the 1990 s, before decreasing in the 2000 s, reaching a nadir around 2012, and increasing again within the last decade to levels in 2020 that were similar to their highest levels in the early 2000 s. In 2020, neonatal deaths from HIV-attributable preterm birth exceeded direct HIV/AIDS infant deaths <1 year in sub-Saharan Africa, and by 5-25 fold in countries with a high HIV prevalence.

Conclusions: Neonatal deaths due to HIV-attributable preterm birth are increasing and now exceed direct HIV/AIDS infant deaths <1 year in sub-Saharan Africa, particularly in countries with a high HIV prevalence.