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Objective: We developed Healthy Families-PrEP to support perinatal women to use HIV prevention strategies.

Design: Single-arm study to evaluate PrEP use among pregnant women exposed to the intervention.

Methods: We offered safer conception counselling, including TDF/FTC as PrEP with adherence support (Healthy Families-PrEP) for women planning for pregnancy in South Africa with a partner with HIV or unknown serostatus. Women completed pregnancy and HIV testing quarterly and were followed for 1 year or until pregnancy end. For those initiating PrEP, electronic pillcap data and plasma were collected. We described PrEP adherence by proportion of days with pillcap openings and proportion of women with detected (≥10ng/ml) plasma tenofovir.

Results: From November 2017 to January 2020, 326 women with median age 24 years [interquartile range (IQR) 22-27] enrolled. Partner HIV-serostatus was unknown by 316 (97%). Over 3204 person-months of follow-up, 56 women became pregnant. Twenty-six women used PrEP during pregnancy and opened pillcaps on a mean of 53.1% [95% confidence interval (CI) 46.9-59.3%] of days. Plasma tenofovir was detected among 25, 15.4, and 12.5% of women providing samples during months 0-3, 4-6, and 7-9. No HIV seroconversions were observed.

Conclusion: We observed low-pregnancy incidence. Counselling may have encouraged delayed pregnancy plans; some women may have exaggerated pregnancy plans to enroll. About half of pregnant women used PrEP and took over half of doses by pillcap. Fewer than 25% had tenofovir detected, likely reflecting pregnancy-related pharmacokinetics and adherence challenges. High interest in pregnancy PrEP use highlights the need to optimize adherence support and prevention choice.

Objective: To discover microRNA (miRNA)-RNA transcript interactions dysregulated in brains from persons with HIV-associated neurocognitive disorder (HAND), we investigated RNA expression using machine learning tools.

Design: Brain-derived host RNA transcript and miRNA expression was examined from persons with or without HAND using bioinformatics platforms.

Methods: By combining next generation sequencing, droplet digital (dd)PCR quantitation of HIV-1 genomes, with bioinformatics and statistical tools, we investigated differential RNA expression in frontal cortex from persons without HIV [HIV(-)], with HIV without brain disease [HIV(+)], with HAND, or HAND with encephalitis (HIVE).

Results: Expression levels for 147 transcripts and 43 miRNAs showed a minimum four-fold difference between clinical groups with a predominance of antiviral (type I interferon) signaling-related, neural cell maintenance-related, and neurodevelopmental disorder-related genes that was validated by gene ontology and molecular pathway inferences. Scale of signal-to-noise ratio (SSNR) and biweight midcorrelation (bicor) analyses identified 14 miRNAs and 45 RNA transcripts, which were highly correlated and differentially expressed ( P  ≤ 0.05). Machine learning applications compared regression models predicated on HIV-1 DNA, or RNA viral quantities that disclosed miR-4683 and miR-154-5p were dominant variables associated with differential expression of host RNAs. These miRNAs were also associated with antiviral-related, cell maintenance-related, and neurodevelopmental disorder-related genes.

Conclusion: Antiviral as well as neurodevelopmental disorder-related pathways in brain were associated with HAND, based on correlated RNA transcripts and miRNAs. Integrated molecular methods with machine learning offer insights into disease mechanisms, underpinning brain-related biotypes among persons with HIV that could direct clinical care.

Objective: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa.

Design: We conducted an open-label, individually randomized clinical trial.

Methods: Using a two-armed approach, PWH who smoke were randomized to receive either intensive antismoking behavioral counselling or intensive antismoking behavioral counseling plus c-NRT (nicotine patches augmented by nicotine gum). Self-reported smoking abstinence was biochemically validated with exhaled breath carbon monoxide (CO) and urine cotinine at 6 months. Recruitment, provision of trial interventions, and follow-up of participants took place in March 2014 through June 2016.

Results: We randomly assigned 280 participants to the behavioral counseling arm and 281 participants to the behavioral counseling + c-NRT arm. Four hundred and thirty-eight (78%) participants were men and 123 (22%) were women. For our primary outcome of biochemically verified abstinence at 6 months, 41 (15%) were quit in the behavioral counseling + c-NRT arm vs. 28 (10%) in the behavioral counseling arm, resulting in a 5% [95% confidence interval (CI) -1 to 10%] absolute difference in relative risk and an adjusted odd ratio of 1.47 (95% CI 0.86-2.52) comparing the behavioral counseling + c-NRT to the behavioral counseling arm.

Conclusion: Although our results did not reach statistical significance, we found augmentation of behavioral counseling with c-NRT to increase smoking abstinence at 6 months, which is consistent with performance in the general population. PWH in low-resource settings may benefit from the addition of c-NRT to existing tobacco cessation interventions.

Background: Transactional sexual relations in the absence of condom use is a well established behaviour that strongly contributes to HIV transmission if the infected person is not virally suppressed. In this study, we determined the trends and factors associated with viral load non-suppression (VLNS) among treatment-experienced FSWs in Kenya.

Methods: This retrospective cohort study used data collected from seven sex workers' outreach clinics between 2015 and 2022. VLNS trends were determined using the Modified Mann-Kendall test, and the effects of covariates on VLNS odds were examined using generalized estimating equations (GEE) with a logit link.

Results: Twelve thousand one hundred and seventeen viral load tests were performed on samples collected from 1947 FSWs. The prevalence of VLNS decreased from 25.5% [95% confidence interval (CI) 17.6-34.6] in 2016 to 4.3% (95% CI 2.5-6.7) in 2021. The odds of VLNS decreased by 9% per year during the study period in the multivariable GEE analysis adjusted for covariates [regimen, age, and sex worker outreach program (SWOP) clinic], [odds ratio (OR) 0.91, 95% CI 0.84-0.98; P  = 0.005]. Age was a significant factor associated with VLNS, with younger women (18-24 years) having 2.2 times higher odds of VLNS (OR 2.15 95% CI 1.10-4.20; P  = 0.025) than those aged over 55 years (reference). Participants on dolutegravir (DTG)-based cART regimen had 64% lower odds of VLNS (OR 0.36, 95% CI 0.25-0.52; P  < 0.001) compared to those on protease inhibitor-based regimen.

Conclusion: There is strong evidence of decreasing population-level viraemia among FSWs during the study period. To maintain the trend, it is necessary to continue supporting SWOP clinics in order to provide HIV treatment services to this key population.

Objective: HIV-1 remains a global challenge, especially in high-prevalence areas like South Africa. This study explores the relationship between inflammation and metabolism in people with HIV, focusing on immune markers and the tryptophan-kynurenine (Trp-Kyn) pathway.

Design: This is a cross-sectional, observational study exploring the associations between peripheral inflammation and metabolism in treatment-naive South African people with HIV.

Methods: We examined immune markers (hsCRP, suPAR, IL-6, NGAL, and sCD163) and Trp-Kyn metabolites (QUIN, Trp, Kyn, Trp/Kyn ratio, and kynurenic acid) in n = 69 treatment-naive South African people with HIV using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and various assays.

Results: We observed significant associations between immune markers and Trp-Kyn metabolites. IL-6 was negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P = 0.005). hsCRP was positively associated with QUIN (P = 0.036). suPAR showed significant negative associations with Trp (P = 0.036), positive associations with the Kyn/Trp ratio (P < 0.001), and QUIN (P = 0.007). sCD163 negatively associated with Trp (P < 0.001) and positively with the Kyn/Trp ratio (P < 0.001). When participants were stratified by inflammation levels (based on CRP), IL-6 (P = 0.002), QUIN (P = 0.009), and Kyn (P = 0.032) were significantly higher in the high inflammation group. Specific associations were observed only in certain groups, such as IL-6 negatively associating with Trp and kynurenic acid in the high inflammation group, and suPAR associating negatively with Trp in the low inflammation group.

Conclusions: These exploratory findings provide further insight into how peripheral inflammation and metabolism are interrelated in South African people with HIV, potentially guiding future therapeutic strategies."

A retrospective case-controlled study compared pregnancy outcomes between people with perinatally acquired HIV (PaHIV), horizontally acquired HIV (HaHIV), and those without HIV. PaHIV were more likely to be viraemic in early pregnancy than HaHIV. When matched for age and ethnicity, babies born to PaHIV were more likely to be premature, small for gestational age, delivered by caesarean section and require enhanced neonatal and social care involvement than infants born to age/ethnically matched HIV-uninfected individuals.

Objectives: Substance use disorders (SUDs) are a significant public health concern across the United States and may pose a risk to achieving sustained viral suppression (SVS) in people with HIV (PWH). This study aims to examine the association between SUDs and SVS among PWH.

Design: Using electronic health records from the South Carolina Department of Health, we conducted a retrospective study of adults with HIV who were diagnosed between January 2006 and December 2019.

Methods: The impact of SUDs on SVS was assessed using generalized linear mixed model. Potential confounders included age, sex, chronic diseases history, etc. Stepwise selection was performed to decide the confounders included in the final model, and the optimal correlation structure was determined by Akaike information criterion.

Results: Of the 9412 eligible participants, 7481 (79.48%) had reached SVS status during their follow-up periods. SUDs related to alcohol [adjusted odds ratio (AOR) = 1.70, 95% confidence interval (CI): 1.46-1.98], cannabis (AOR = 1.62, 95% CI: 1.35-1.95), cocaine (AOR = 1.95, 95% CI: 1.60-2.37), opioid (AOR = 1.91, 95% CI: 1.13-3.23), and tobacco (AOR = 1.80, 95% CI: 1.69-1.92) were negatively associated with SVS. Individuals with chronic conditions such as cardiovascular disease (AOR = 0.31, 95% CI: 0.29-0.33), diabetes (AOR = 0.49, 95% CI: 0.41-0.59), and cancer (AOR = 0.47, 95% CI: 0.38-0.58) showed a higher likelihood of maintaining SVS.

Conclusion: This large cohort study of PWH with extended follow-up highlights the negative impact of SUDs on maintaining SVS. Long-term strategies for reducing substance use could support SVS in PWH.

Background: Limited systematic data exist on HF phenotypes in contemporary HIV care, and no prior multicenter studies have investigated physician-adjudicated phenotypes and etiologies of HF in PWH.

Methods: We adjudicated HF events and sub-phenotypes occurring between January 1, 2010 and December 31, 2021 at two large urban clinical centers within the CFAR Network of Integrated Clinical Systems (CNICS) cohort. Using Cox proportional hazard regression, hazard ratios were calculated to examine associations of HIV-specific and cardiometabolic risk factors with incident HF among PWH. Exploratory analyses investigated presence of physician-adjudicated ischemic and non-ischemic etiologies of HF.

Results: Of 402 individuals with events screened as possible HF, 289 were adjudicated as HF. Of these 289, 77 were prevalent at baseline and 212 were incident. Higher viral load and lower CD4 T cell count were associated with incident HF. In addition, older age, smoking, hypertension, diabetes mellitus, history of myocardial infarction (MI), and renal insufficiency were associated with higher HF risk. Nonischemic HF etiologies were more common than ischemic, and HF with reduced ejection fraction (HFrEF) was more common than preserved ejection fraction (HFpEF). Despite distinct demographic and risk factor compositions between the two sites, HF phenotypes were similar.

Conclusion: HIV viremia, low CD4 T cell count, traditional CVD risk factors, and renal insufficiency were associated with higher risk for HF. The predominant HF subtype was non-ischemic HF. While further studies are needed, our findings suggest HF prevention and management in PWH will require addressing complex interactions between HIV-related and traditional CVD risk factors.