AIDS最新文献

We deployed the VANTAGE (VAN for Transmissible Agent Genomic Epidemiology) mobile system in Lviv, Ukraine, demonstrating end-to-end sequencing of dried blood spot samples within a clinic van usually serving de-occupied and frontline regions. HIV-1 pol sequences were obtained from 50% of samples, all subtype A6. Median time to 100× coverage was 38 min. Phylogenetic analysis revealed a local transmission cluster including a displaced person and the non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation E138A, supporting real-time HIV genomic surveillance in humanitarian crises.

Introduction: We assessed implementation of tuberculosis (TB) services among children living with HIV (CLHIV) (<15 years) in 16 African countries supported by US President's Emergency Plan for AIDS Relief (PEPFAR) between October 2018 and September 2022 [fiscal year (FY) 2019-FY2022).

Methods: We reviewed PEPFAR TB indicators describing symptom screening, treatment initiation, and TB preventive treatment (TPT) initiation and completion among CLHIV. We describe performance of these measures at semi-annual time points from FY2019 to FY2022 with stratification by age, sex, geographic region, and antiretroviral therapy (ART) status for FY2022.

Results: During FY2019-FY2022, the proportion of CLHIV with a positive TB symptom screen was low, ranging from 2.5 to 4.1%, while TB treatment initiation among those who screened positive fluctuated from 19 to 43%. Similarly, TPT initiation among CLHIV newly initiating ART fluctuated during this time, ranging from 13 to 37%, while TPT completion rose from 55 to 85%. In 2022, 80% of CLHIV were screened for TB and 3.6% had a positive symptom screen. Among those, 15% of CLHIV already on ART and 40% of CLHIV newly initiating ART were started on TB treatment. In 2022, among CLHIV newly initiating ART, 37% started TPT within 6 months, and 84% completed the full course of TPT.

Conclusion: TB screening and screening positivity were suboptimal. CLHIV starting TB treatment following positive symptom screen was higher than expected, especially among those newly initiating ART. Most CLHIV did not start TPT within 6 months of ART initiation. These findings suggest that programs are missing opportunities to diagnose and prevent TB in CLHIV.

Objective: To assess hepatitis B virus (HBV) monitoring, HBV reactivation and hepatitis flares during tenofovir interruptions among people with HIV and HBV.

Design: Cohort study of electronic health records.

Methods: All tenofovir (tenofovir disoproxil fumarate and tenofovir alafenamide) interruptions among people with HIV and positive HBV surface antigen (HBsAg) or positive HBV core antibody (HBcAb) were categorized by reactivation risk [high: HBsAg+; moderate: HBsAg-/HBcAb+/surface antibody (HBsAb) negative; low: HBsAg-/HBcAb+/HBsAb+]. Incidence rates of HBV reactivation and hepatitis flare were assessed with Poisson regression.

Results: Among 5343 individuals with HIV and HBV, there were 6252 tenofovir interruptions (11% high risk, 19% moderate risk, 69% low risk). During the interruptions, HBV DNA/HBsAg testing was infrequent (high: 52%/25%; moderate: 8%/31%, low: 5%/28%), although alanine transaminase (ALT) testing was performed during nearly all interruptions. The HBV reactivation rate was 9.59 per 100 person-years [95% confidence interval (CI): 7.91-11.64] during high-risk, 0.58 (0.36, 0.91) during moderate-risk, and 0.04 (0.02, 0.11) during low-risk interruptions. The HBV reactivation with hepatitis flare incidence rate was much lower, especially in the high-risk group (3.06 per 100 person-years; 95% CI: 2.19-4.29).

Conclusions: In this large US cohort of people with HIV and HBV, tenofovir interruptions were common and HBV monitoring was sub-optimal. HBV reactivation rates were highest among the high-risk group, but much lower among the moderate-risk and low-risk groups. However, some reactivations were likely missed due to low monitoring frequency. Primary and HIV care providers must incorporate HBV monitoring in their standard of care and proceed with caution if considering a tenofovir interruption for people with HIV and HBV.

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.

Background: HIV genetic diversity has increased over time, with recombinant forms becoming more prevalent and complicating subtype classification and surveillance, particularly in low-and-middle income countries (LMICs). Accurate subtyping is critical for surveillance, vaccine design, and cure strategies, but its reliability depends on methodological choices — the genomic region sequenced, laboratory methods employed, and the subtyping tools used. This study evaluates how these methodologies influence reported recombinant form prevalence across regions.

Methods: This systematic review included over 400 peer-reviewed studies published between January 2010 and June 2021 that reported HIV subtype prevalence across diverse geographic regions. Data on subtyping methodologies were also extracted. To explore associations with recombinant form prevalence, three generalized linear mixed models were developed for meta-analysis.

Results: Our findings show that Sanger sequencing of the pol region, analyzed using tools from the Los Alamos National Laboratory, remains the most widely used subtyping methodology. Over time, there has been a steady increase in studies reporting HIV subtype diversity. In the meta-analysis, specific genome regions and subtyping tools were positively associated with recombinant form prevalence. Despite controlling for region, certain areas remained positively or negatively associated with recombinant form prevalence.

Conclusions: This review highlights the methodological challenges of HIV subtyping and recombinant form detection, which are critical for surveillance, vaccine development, and cure strategies. We highlight the urgent need for accessible, reliable subtyping tools and enhanced capacity-building—particularly in LMICs, where high viral diversity overlaps with the greatest burden of disease.

Background: Children and adolescents with HIV previously taking ritonavir-boosted lopinavir (LPV/r)-based antiretroviral therapy (ART) were recently programmatically transitioned to dolutegravir (DTG)-based ART in Lesotho, southern Africa. We investigated associated changes in treatment satisfaction and potential side effects.

Methods: This single-center prospective cohort study enrolled participants <18 years transitioned from LPV/r- to DTG-based ART during the national programmatic DTG rollout in 2022-2023. Virally suppressed participants ≥6 years able to handle a sleep diary and actigraphy were eligible for additional sleep monitoring. Enrollment occurred 2 weeks before (with actigraphy) or at (without actigraphy) transition with follow-up until 4 weeks post-transition. Co-primary endpoints were i) change in treatment satisfaction, using the HIV Treatment Satisfaction Questionnaire change version (HIVTSQc; Teen and Parent versions) at 4 weeks, and ii) difference in mean sleep period length over a two-week period before and after transition (only actigraphy participants). Secondary endpoints assessed treatment satisfaction status, gastrointestinal symptoms, depressive symptoms, and additional sleep measures.

Results: Among 245 participants with transition and 4-week data, 115 (47%) were female and median age was 11.1 (interquartile range 8.9-13.6) years. HIVTSQc outcomes favored DTG, with 88/92 (96%) HIVTSQc-Teen and 149/151 (99%) HIVTSQc-Parent responses indicating being "much more satisfied now" post-transition. Among 69 (28%) actigraphy participants, mean sleep period length was 9.0 hours (standard deviation [SD] 1.0) before and 9.2 hours (SD 1.0) 2-4 weeks post-transition (mean difference 0.2, 95% CI 0.0-0.4). Secondary outcomes did not change meaningfully.

Conclusions: Observed treatment satisfaction and tolerability support the rollout of DTG in pediatric HIV care.

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.

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/mm3 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/mm3 and increased with lower CD4 counts (≤100 cells/mm3, 15% (95% CI 11 - 19); ≤50 cells/mm3, 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.

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.

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.