AIDS最新文献

Background: The accuracy of Fatty Liver Index (FLI) and Hepatic Steatosis Index (HSI) to predict liver steatosis in people living with HIV (PLWH) remains poorly studied in low- and middle-income countries (LMICs). We assessed their diagnostic performances in a multiregional cohort.

Methods: This cross-sectional analysis included PLWH aged ≥40 years on antiretroviral therapy for ≥6 months at enrolment (2020-2023) in the Sentinel Research Network (SRN) of IeDEA consortium, across 12 HIV clinics in Asia-Pacific, Americas, and central, East, southern and West Africa regions. Liver steatosis was defined based on Controlled Attenuation Parameter (CAP) ≥248 dB/m using vibration-controlled transient elastography. HSI was evaluated in the overall population, while FLI was assessed and compared to HSI in a subset of participants with available data. Model discrimination was assessed using area under the receiver operating characteristic curve (AUROC) and model calibration with calibration plots. A decision curve analysis was performed to compare their clinical utility.

Results: Among 2,195 PLWH assessed using CAP, 624 (28.4%) presented with liver steatosis. HSI showed acceptable discriminative ability (AUROC = 0.74) but poor calibration, generally overestimating the risk, except in Asia-Pacific region. FLI performed better than HSI (AUROC = 0.80, p  < 0.001), and demonstrated good calibration except in sub-Saharan Africa. Both scores showed high clinical utility, with FLI demonstrating a greater net benefit when compared with HSI.

Conclusion: FLI demonstrated higher accuracy and clinical utility within a subgroup of regions. However, the limited performance of FLI and HSI in sub-Saharan populations highlights the need to adapt existing tools or develop new predictive models tailored to regional contexts.

Objective: Long-acting injectable cabotegravir + rilpivirine (CAB + RPV) streamlines HIV care but may be limited by injection-site reactions (ISRs) and pharmacokinetic (PK) variability. Point-of-care ultrasound (POCUS) can visualize tissue planes in real time, yet its impact on drug exposure and tolerability remains unclear.

Design: This is a prospective crossover study in 51 virologically suppressed adults receiving bimonthly CAB + RPV who underwent one ventrogluteal injection guided by POCUS, followed by routine unguided ventrogluteal injections.

Methods: Trough and one month post-injection plasma concentrations were quantified by LC-MS/MS. ISRs were evaluated with a validated questionnaire. Mixed-effects models compared PK and tolerability outcomes.

Results: We analyzed 143 trough and 46 one month post-injection samples. Intramuscular deposition was confirmed in 75% of ultrasound-guided injections. Median trough CAB concentrations were 525 (340-886) ng/mL with ultrasound guidance versus 637 (399-862) ng/mL without, and RPV troughs were 130 (114-151) versus 135 (118-152) ng/mL (all P > 0.10); one month post-injection concentrations were also similar. Ultrasound guidance reduced the overall ISR burden by 16% (RR 0.84, 95% CI 0.72-0.97; P = 0.018), with fewer reports of induration (8% vs. 19%; P = 0.026) and redness (6% vs. 15%; P = 0.034).

Conclusions: These findings support ultrasound guidance as a practical approach to improve injection accuracy and patient comfort, particularly in individuals at higher risk of poor intramuscular deposition or prior tolerability issues.

Objectives: People living with HIV (PLWH) have an increased risk of cardiovascular disease (CVD), but longitudinal data from middle-income settings remain limited. This study examined the association between HIV, antiretroviral therapy (ART), and pulse wave velocity (PWV), a marker of arterial stiffness and CVD risk.

Design: A longitudinal analysis from the Ndlovu Cohort Study, South Africa.

Methods: The study included 705 participants (325 PLWH, 81% on ART at baseline, 19% initiating ART at baseline, and 380 HIV-negative people. Demographic data, HIV/ART status, and covariates were collected at baseline, while PWV was measured at 12 and 36 months. Mixed-effects models were used to analyse PWV changes over time, adjusting for age, sex, and systolic blood pressure (SBP). Results were reported as beta coefficients (β) with 95% confidence intervals (CI).

Results: At baseline, PLWH were older and predominantly female (67%) compared to HIV-negative people. At 12 months, median PWV was higher in PLWH (7.3 m/s) than in HIV-negative people (7.0 m/s, p=0.001). Over 36 months, PWV increased by 0.30 m/s in PLWH and 0.20 m/s in HIV-negative people (p = 0.002). ART-naïve individuals had the largest PWV increase after starting ART (6.8 m/s at 12 months to 7.4 m/s at 36 months, p = 0.001). HIV (β=0.65, 95% CI: 0.24-1.06, p = 0.002) and time (β=0.31 m/s per year, p < 0.001) were significantly associated with higher PWV.

Conclusions: PWV increased over time, particularly in PLWH, with ART initiation linked to rapid increases. These findings highlight the need for early CVD risk monitoring, especially post-ART initiation, in resource-limited settings.

Objectives: We examined whether effects of an agricultural livelihood intervention on food insecurity and psychosocial outcomes remained robust in pregnant compared to non-pregnant women living with HIV, and whether potentially negative associations between pregnancy and these outcomes were alleviated by the intervention.

Design: Secondary analysis of the Shamba Maisha cluster-randomized controlled trial (N = 396 women; NCT02815579). The intervention included agribusiness training and supplies.

Methods: Food insecure women with HIV in Kenya were followed for 24 months between 2016 and 2019. Food insecurity, empowerment, social support, depression, HIV stigma, and intimate partner violence were collected at all visits. We estimated (1) the effect of the intervention on trends for each outcome via mixed-effects regression, separately for women who did and did not become pregnant during follow-up, and (2) whether trends differed by pregnancy status, separately by arm and adjusted for demographic factors.

Results: In comparison to controls, the intervention was associated with a greater decline in food insecurity among women who became pregnant (3.35 points, 95% CI: -5.63, -1.06) and who did not become pregnant (3.43 points, 95% CI: -4.34, -2.52). Effects on psychosocial outcomes were also comparable in pregnant and non-pregnant women. Having an incident pregnancy was associated with disempowerment among controls (difference in trend -0.22, 95%CI -0.44, -0.00) but not in the intervention arm.

Conclusions: We observed comparable benefits of an agricultural livelihood intervention on food security and psychosocial outcomes regardless of pregnancy status. Agricultural livelihood interventions may hold promise for improving pregnancy outcomes through improved maternal food security.

Background: In sub-Saharan Africa (SSA), people with HIV continue to present with advanced HIV disease (AHD), putting them at high risk of life-threatening opportunistic diseases. We aimed to estimate mortality among this population.

Methods: We conducted a systematic review and meta-analysis of studies reporting one-year mortality among adults living with HIV and presenting to care with CD4 counts ≤200 cells/mm 3 in SSA. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies (comprising >500 participants) published between January 1, 2016, and March 21, 2025. Screening and data extraction were done in duplicate. Pooled mortality proportions across CD4 count and time strata were calculated using a generalised linear mixed model. Risk of bias was assessed using a modified Newcastle-Ottawa scale. The protocol is registered with PROSPERO, CRD42023451498.

Results: Thirty-six studies with 313,362 participants were included. The weighted median age was 35 years, 64% were female, and 98.9% were antiretroviral therapy-naive. One-year mortality was 12% (95% CI 8 - 16) among people with CD4 count ≤200 cells/mm 3 and increased with lower CD4 counts (≤100 cells/mm 3 , 15% (95% CI 11 - 19); ≤50 cells/mm 3 , 20% (95% CI 12 - 31)). Most deaths occurred within the first three months after AHD presentation. Heterogeneity was substantial. Risk of bias was high in 18 (50%) of 36 included studies.

Discussion: There is high one-year mortality among people presenting with AHD in SSA. It is a priority to identify AHD with CD4 testing, improve retention in care, and evaluate additional interventions to reduce mortality in this population.

Objective: Chronic inflammation may be associated with cognitive disorders in people with HIV (PWH) on antiretroviral treatment (ART). We examine associations between cognitive function (CF) and plasma biomarkers measured in PWH and demographically-similar people without HIV in the POPPY study.

Design: Prospective longitudinal cohort study.

Methods: At baseline and 2-year follow-up, participants completed a cognitive test battery. Global T-scores were derived by averaging domain T-scores. We used linear regression to explore associations between changes in Global T-scores and log-transformed plasma biomarkers of neuronal injury, systemic inflammation and innate immune activation. We explored whether effects of biomarkers differed by HIV status.

Results: 349 participants were included (73% PWH, median [interquartile range, IQR] age 54 [50-60] years, 85% male, 95% white). Among PWH, 98% were on ART, 93% had HIV-RNA ≤ 50 copies/mL and median [IQR] CD4+ count was 627 [490,792] cells/mm 3 . Mean (standard deviation (SD)) baseline Global T-score was 47.7 (5.9) which increased to 48.9 (5.5) after a median [IQR] follow-up of 26 [24,29] months. Lower average increases in Global T-scores were seen in those with higher MIP-1α concentrations (parameter estimate: -0.27 [95%CI:-0.51,-0.03] /10% increase) and sCD14 (-0.17 [-0.30,-0.03]), though only MIP-1α (-0.46 [-0.58,-0.10]) remained significant after adjustment. There was no evidence that the associations differed by HIV status.

Conclusion: Higher MIP-1α and sCD14 showed small associations with lower average increases in Global T-scores, with no differences by HIV status or inflammatory clusters, highlighting the multifactorial influences on cognitive trajectories in people ageing with and without HIV.

Background objectives: To compare cognitive performance between adolescents with and without perinatally acquired HIV and to evaluate the association between oral health and cognitive performance.

Methods: A cross-sectional analysis was conducted using baseline data from a study of 118 age- and sex-matched adolescents (59 PHIV, 59 HUU) aged 9.5-16.5 years in Benin City, Nigeria. Cognitive function was assessed using two tablet-based tools: NeuroScreen and the NIH Toolbox Cognition Battery. Oral health was evaluated via clinical examination using the Decayed, Missing, and Filled Teeth (DMFT) and oral hygiene questionnaires. ANOVA and ANCOVA were used to examine associations between HIV status, oral health, and cognitive outcomes.

Results: Adolescents with PHIV demonstrated significantly lower cognitive performance compared to their HUU peers, particularly in processing speed, executive function, and language domains. NeuroScreen assessments revealed longer completion times in Trail Making tasks (TM1: 44.8 vs 37.7, adjusted p = 0.039; TM2: 51.4 vs 42.5, adjusted p = 0.018; TM3: 25.6 vs 19.8, adjusted p = 0.027) and lower scores in Visual Discrimination (VD2: 19.3 vs 21.9, adjusted p = 0.002) and Number Speed tests (NSd: 53.1 vs 46.1, adjusted p = 0.008) among adolescents with PHIV. In addition, NIH Toolbox results indicated lower scores across all cognitive domains for adolescents with PHIV. Higher DMFT scores were associated with poorer executive function, and this relationship was observed only among adolescents with PHIV in stratified analyses, across both the NeuroScreen and NIH Toolbox assessments.

Conclusion: Adolescents with PHIV exhibited notable neurocognitive deficits and a tendency toward poorer oral health compared with uninfected peers. Poor oral health correlated with diminished cognitive performance, underscoring the need for integrated care models that address both neurocognitive and oral health in youth living with HIV.

Objective: To assess the prevalence and patterns of treatment-emergent resistance-associated mutations (RAMs) in people with HIV (PWH) with ≥1 prior regimen experiencing virologic failure (VF) with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), dolutegravir/lamivudine (DTG/3TC), or cabotegravir/rilpivirine (CAB + RPV) in an observational setting.

Design: A noninterventional, multicenter, retrospective, observational study was conducted between January 1, 2022, to December 31, 2024 using a national French multicenter database of genotypic resistance assays performed at confirmed VF.

Methods: VF was defined as 2 consecutive HIV-1 plasma viral loads of >50 copies/mL. Genotypic resistance assays were performed using Sanger sequencing. Treatment-emergent RAMs were characterized using the 2024 ANRS algorithm. Clinical history, virologic history, and demographic data were collected from medical records during standard clinical follow-up.

Results: A total of 6523 PWH were followed over 3 years. The prevalence of VF during follow-up was 6% with B/F/TAF, 5% with DTG/3TC, and 5% with CAB + RPV. The prevalence of treatment-emergent RAMs at VF were 3% with B/F/TAF, 15% with DTG/3TC, and 32% with CAB + RPV. Dual treatment-emergent integrase strand transfer inhibitor (InSTI) and nucleoside reverse transcriptase inhibitor (NRTI) RAMs were observed with B/F/TAF and DTG/3TC, while dual treatment-emergent nonnucleoside reverse transcriptase inhibitor (NNRTI) and InSTI RAMs were observed with CAB + RPV.

Conclusions: The overall prevalence of VF was low for all regimens. B/F/TAF was associated with a numerically lower prevalence of RAMs at VF compared with DTG/3TC and CAB + RPV. These observational findings highlight the importance of monitoring resistance patterns to optimize HIV treatment outcomes.

Objective: HIV-pre-exposure prophylaxis (PrEP) implementation can be examined by the PrEP care continuum that defines steps toward effective HIV prevention. We examined the PrEP continuum among gay, bisexual and other men who have sex with men (GBMSM) in the Netherlands and in Amsterdam.

Design: Cross-sectional study combining multiple data sources.

Methods: The following steps of the PrEP care continuum were estimated for 2023: 1) GBMSM not living with HIV, 2) accessed sexual health services, 3) PrEP-eligible, 4) PrEP-intention, 5) current PrEP use, and 6) PrEP continuation. The number of GBMSM progressing through each step were estimated and percentages were calculated using the nominator of the previous step.

Results: An estimated 746,061 (Uncertainty Interval (UI) 634,503-856,079) GBMSM were not living with HIV in the Netherlands. Of those, 44,911 (6%, UI 5-7%) accessed sexual health services, of whom 34,895 (78%, UI 71-86%) were PrEP-eligible. We estimate that 22,002 (63%, UI 49-78%) of those had intention to use PrEP. Of those with PrEP-intention, 12,341 (56%, UI 47-69%) currently used PrEP and 10,097 (82%) of those continued PrEP. Of those who accessed sexual health services, 23% continued PrEP in the Netherlands, and 30% in Amsterdam.

Conclusions: When having accessed sexual health services, retention in the PrEP care continuum was high, except for 'PrEP-intention' and 'current use' on the national level. To optimize PrEP implementation, targeted interventions to close this gap and annual monitoring of the PrEP care continuum using standardized resources are needed.

Objective: Investigate whether antiretroviral metabolites tenofovir-diphosphate (TFVdp) and lamivudine triphosphate (3TCtp) in dried blood spots (DBS) are reliable markers of ART adherence by predicting viral suppression in postpartum women living with HIV in resource-limited settings.

Design: Prospective cohort study.

Methods: Pregnant women diagnosed with HIV who started ART from 10/2018-07/2021 and participated in a video-based intervention trial were included in this substudy. Whole blood samples were collected 12 months after ART initiation to measure viral load, TFVdp, and 3TCtp. Ability of TFVdp and 3TCtp to identify HIV-suppressed women was assessed using area under the curve (AUC) in receiver operating characteristic (ROC) analysis and compared to self-reported adherence data.

Results: We included 588 women, with a mean age of 27 years. TFVdp and 3TCtp concentrations were detected in 82% (482/588) and 77% (455/588) of samples, respectively. Daily TFVdp dosing concentrations (≥1,400 fmol/punch) were observed in 389 women of whom 86% (333/389) were HIV suppressed compared with only 22% (28/128) in those taking fewer than two doses per week; similar results were observed for 3TCtp (TFVdp OR = 21.2, 95% CI: 12.8-35.2; 3TCtp OR = 7.5, 95% CI: 3.7-15.3). ROC analysis revealed identical AUCs of 0.83 (95% CI: 0.78-0.87) for both metabolites, which was significantly higher than the AUC for self-reported adherence data (0.58, 95% CI: 0.53-0.63). Approximately one-third of women had TFVdp levels >2,800 fmol/punch, which was higher than expected for daily dosing.

Conclusions: TFVdp and 3TCtp concentrations measured in DBS samples are reliable markers of ART adherence and outperform self-reported adherence data. High TFVdp levels warrant further investigations.