AIDS最新文献

Objective: Fixed dose combination (FDC) dolutegravir (DTG) plus rilpivirine (RPV) is an approved antiretroviral treatment regimen for people with HIV. The steady-state pharmacokinetics of FDC DTG+RPV in hemodialysis has not been previously studied.

Design: We performed a single-center, prospective evaluation of the steady-state pharmacokinetics of FDC DTG +RPV in four adults without HIV either requiring hemodialysis and in four matched participants with normal renal function.

Methods: All participants received FDC DTG (50 mg)+RPV (25 mg) daily for 10-14 days with food before undergoing an intensive 24 h pharmacokinetic evaluation (performed between dialysis days for those requiring HD). Plasma drug and metabolite concentrations were measured using a validated UHPLC/MS/MS. Descriptive pharmacokinetic parameters were calculated.

Results: The hemodialysis and normal renal function participants (each group with two men and two women) were of similar ages (range, 50-60 years) and BMI (range, 18.5-34.5 kg/m 2 ). No participant experienced serious or grade 3-4 adverse events; there were no study discontinuations. The AUC 0 - τ mean (SD) ratios of hemodialysis to normal renal function for DTG and RPV were 1.1 (0.4) and 1.1 (0.9), respectively. The mean (SD) Cmin for DTG and RPV in the hemodialysis group were 1033 (252) and 49 (18) ng/ml, respectively.

Conclusion: Hemodialysis did not lead to clinically appreciable differential exposures to DTG and RPV. Exposures throughout the dosing interval were greater than the reported protein-binding-adjusted IC90 efficacy values for DTG (64 ng/ml) and RPV (12 ng/ml) in all participants. These data suggest no dosing modifications are needed for the FDC DTG+RPV regimen in hemodialysis.

Objective: This study aimed to estimate the latent frailty trajectories and identify corresponding predictors (sociodemographic, HIV-related, comorbidities, and behavioral) among a cohort of people with HIV (PWH).

Design: Longitudinal observational study using latent class growth modeling.

Methods: Nine hundred and seventy-six PWH aged 40 years and older with frailty measured from at least two visits within the ACTG HAILO cohort were included. Frailty components included weakness, physical activity, weight loss, exhaustion, and slowness. Latent class growth models were estimated to capture change in frailty over time; multinomial logistic regression was used to estimate associations between predictors and frailty trajectory class.

Results: At baseline, participants were M  = 51.5 years old ( SD  = 7.5), 81% male ( n  = 783), 48% White non-Hispanic ( n  = 461), and 20% Hispanic ( n  = 195). Latent class growth models identified three frailty trajectories: sustained robustness ( n  = 811; 83%), worsening frailty ( n  = 79; 8%), and frailty improvement ( n  = 86; 9%). Older age, race, sex at birth, select comorbidities (cardiovascular disease, depression, type 2 diabetes), and behavioral characteristics (physical activity, smoking, and alcohol) were associated with fluctuations in frailty trajectories over time ( P  < 0.05).

Conclusion: Modifiable factors such as managing comorbidities and promoting physical activity present ideal opportunities for future interventions to prevent or slow the progression of frailty.

South Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing "Philani Ndiphile" trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age. National progress toward UNAIDS' targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum. Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.

Objective: People living with HIV (PLWH) have increased risk for worse pulmonary function and increased emphysema. HIV has been proposed as a risk factor for respiratory patient-reported outcomes (PROs). We assessed the association of HIV with respiratory symptoms, respiratory health status, and functional exercise capacity.

Design: Systematic review and meta-analysis.

Methods: We searched PubMed, EMBASE, CENTRAL, CDSR, WoS, Scopus, CINAHL, and GIM through November 2023 for studies of people living with and without HIV reporting respiratory PROs. Primary outcomes were activity-limiting dyspnea (defined as Modified Medical Research Council Dyspnea Scale score≥2), respiratory health status by St. George's Respiratory Questionnaire (SGRQ), and exertional capacity by six-minute walking distance (6MWD). We performed random-effects meta-analyses estimating odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs).

Results: We included 89 publications corresponding to 56 studies. HIV was associated with activity-limiting dyspnea (OR 1.67; 95% CI 1.05-2.65), worse respiratory health status (SGRQ MD 2.9 units; 95% CI 0.6-5.2), worse exertional capacity (6MWD MD -58.9 meters; 95% CI -115.3- -2.4), and chronic cough, dyspnea, phlegm, and wheeze (OR 1.38-1.78). Respiratory symptom and adverse respiratory health status risk was greatest in European PLWH. Certainty of evidence was very low, primarily due to studies' observational design and inconsistency.

Conclusions: PLWH have increased risk for worse respiratory PROs. Systematic respiratory PRO assessment should be incorporated into routine clinical care to facilitate active case-finding of chronic lung disease in PLWH. Future studies should longitudinally co-assess objective physiologic measures and respiratory PROs.

Objectives: To explore the prevalence of depressive symptoms and associated factors among reproductive-aged women participating in the Study of Treatment and Reproductive outcomes (STAR) cohort.

Design: Cross-sectional analysis.

Methods: We analyzed baseline data from women with HIV (WWH) and women without HIV (WwoH) but at risk for HIV enrolled in the STAR, a prospective observational cohort of reproductive-aged women in six Southern U.S. states. We used the Center for Epidemiologic Studies Depression (CES-D) scale to measure depressive symptoms. Crude prevalence ratios (PRs) were used to describe depressive symptoms by sociodemographic, substance use, psychological, and reproductive characteristics.

Results: A total of 473 WWH (median age 37, interquartile range [IQR]: 32-42) and 286 WwoH (median age 32, IQR: 26-40) enrolled as of August 2023 in the STAR. Thirty-eight percent of WWH and 34% of WwoH reported a CES-D score ≥ 16 (henceforth "depressive symptoms"; WWH: median score 11, IQR: 5-21 and WwoH: median score 10, IQR: 6-21). Hazardous alcohol use and history of using crack/cocaine were each associated with increased prevalence of depressive symptoms. The prevalence of depressive symptoms rose with each one standard deviation increase in loneliness, perceived stress, and lack of neighborhood safety. In contrast, we found a lower prevalence of depressive symptoms with increasing resilience and social support scores.

Conclusion: Depressive symptoms are common among reproductive-aged women regardless of HIV status. Future analyses will help to confirm these initial findings and begin to identify intervention targets to alleviate depressive symptoms.

Objectives: To measure SARS-CoV-2 antibody seroprevalence within a cohort of adults living with HIV and correlate demographics with response rates to SARS CoV-2 vaccination.

Design: Initial vaccine trials for SARS CoV-2 did not examine efficacy in people with HIV. We undertook the SCAPE-HIV study from April 2021 to November 2022 to focus on vaccine response in this population to guide future vaccine scheduling.

Methods: Participants completed a retrospective questionnaire. Nucleocapsid and spike antibodies to SARS CoV-2 (anti-N and anti-S) were tested. Demographic and HIV factors (CD4, viral load) were correlated with quantitative serological outcomes. Anti-S titres less than 400U/mL were considered low level. Follow-up was performed in a subset post third vaccination.

Results: Six hundred and twelve participants completed the study questionnaire, 520 were included in the final analysis. Most participants received either ChAdOx1-S recombinant vaccine or the BNT162b2 mRNA vaccine for the first 2 doses. Almost all participants (99.2%) in the main group had an anti-S antibody detected above the assay cutoff (>0.8U/mL). Most participants (77.3%) had anti-S titres greater than 400U/mL, with the median titre 1734U/mL. Age over 60 years was significantly associated with lower (<400U/mL) anti-S antibody titre (p < 0.0001).

Conclusions: We demonstrate a high rate of anti-S seropositivity following SARS-CoV-2 vaccination in people with HIV. Age over 60 was the only parameter found to be associated with a lower anti-S antibody titre. Our findings suggest that COVID-19 vaccine scheduling should target older persons living with HIV in line with the general population.

Objective: We assessed the association between early HIV medical care interruption (MCI) and the development of AIDS-defining events (ADEs), serious non-AIDS events (SNAEs), and death among people with HIV (PWH) from the CoRIS cohort.

Design: We included antiretroviral-naive individuals aged at least 18 years at enrollment, recruited between 1 January 2004 and 30 May 2021, and followed-up until 30 November 2023.

Methods: Early MCI was defined as a time interval over 15 months between two consecutive visits, where the first of these visits occurred within the first 15 months of enrollment. We used Poisson regression models to assess the association between early MCI and the outcomes.

Results: Of 14 594 individuals, 1067 (7.3%) experienced an early MCI. Individuals with early MCI showed higher risk of developing ADEs (adjusted incidence rate ratio, aIRR: 2.92; 95% confidence interval (CI) 2.24-3.81) than those who did not. Early MCI was associated with a higher risk of overall mortality (2.15; 95% CI 1.75-2.64), AIDS-related deaths (3.54; 95% CI 2.35-5.44) and deaths due to liver diseases (2.44; 95% CI 1.19-4.98), but was not with mortality due to non-AIDS-defining malignancies (1.20; 95% CI 0.58-2.49). The primary underlying causes of death among individuals with early MCI were AIDS-related deaths (17%), non-AIDS-defining malignancies (11.7%) and liver diseases (10.6%).

Conclusion: Early MCI was associated with an increased rate of ADEs and death, underscoring the need to design and implement public health strategies that bolster retention in care among PWH.

Objective: We sought to determine the prevalence and examine demographic disparities of viral suppression (VS, <200 copies/mL) and awareness of VS status among people with HIV (PWH) on a popular geosocial networking/dating application (GSN-app).

Design: Cross-sectional, observational study.

Methods: U.S. adult PWH were remotely-recruited through a GSN-app to complete a survey from January-September 2024. We assessed the prevalence and correlates of self-reported awareness of VS status and VS using modified Poisson regression with the following variables: demographics, substance use, region, and Ending-the-HIV-Epidemic priority jurisdiction. Laboratory-based viral loads were collected from a sub-sample of the cohort, allowing comparison of laboratory-based VS to self-reported VS.

Results: Among 2,838 geographically diverse participants, 28% were Black, 32% aged 18-34 years, and 36% reported stimulant use. Overall, 94.9% reported knowing their VS status. Younger, Black, and stimulant-using PWH were less likely to know their VS status. When VS status was known, 93.5% reported VS. Younger and stimulant-using PWH were less likely to report VS. Of the sub-sample with laboratory verification (n = 923), 91.6% who self-reported VS demonstrated laboratory-confirmed VS.

Conclusion: This remotely-recruited U.S. national survey showed high self-reported VS among PWH on a popular GSN-app, in high concordance with laboratory-confirmed VS in a sub-sample. Stimulant use was reported by over one-third of participants, with lower reported VS in this group. Inequities in awareness of VS status among younger, Black, and stimulant-using PWH and lower VS among younger and stimulant-using PWH should be ameliorated through targeted care reengagement and adherence interventions, potentially via GSN-apps.

Objective: The Pumwani Sexworker Cohort in Nairobi, Kenya has enrolled >2100 women from 1985 to 2002. A small subset of women enrolled during this period remain HIV uninfected despite high-risk sex work exposures. This study investigated the expression of genes involved in leukocyte movement and migration and their role in HIV resistance.

Methods: Whole blood was collected from 75 HIV uninfected women: 38 HIV resistant women (average of 15.39 negative years) and 37 susceptible new enrollees (average of 1.027 negative years). The mRNA expression of 84 genes was analyzed using a custom RT2 Profiler PCR-array and compared between HIV resistant women and HIV negative susceptible controls. The function and influence of genes with mRNA significantly differentially expressed were analyzed using Ingenuity Pathway Analysis (QIAGEN) and Pathway Studio (Elsevier).

Results: Eighteen genes were significantly up-expressed in HIV resistant women. Among them, 16 genes are involved in the leukocyte movement and migration (p < 0.00001). Among them, 4 genes (CTNNB1, ITGB1, PIK3CA and PTPN11) are involved in transendothelial leukocyte migration signaling (p < 0.00001), 8 genes (CTNNB1, DPP4, ITGB1, PIK3CA, PTPN11, TICAM1, TIMP1, VCAN) are involved in cellular infiltration by leukocytes (p < 0.00001), and 6 genes (CTNNB1, ITGB1, MAP3K4, PIK3CA, PTPN11, TIMP1) are involved in the Leukocyte Extravasation Signaling (p < 0.00001).

Discussion/conclusions: We propose that the HIV resistant women of the PSC may exhibit a unique leukocyte migratory response in dealing with pathogen infection. The potential mechanisms could contribute to the unique leukocyte migratory response: modifications to the PI3K/AKT signaling, extracellular matrix remodeling, integrin structure and function, and activation of T-cell receptors.

An increasing number of people living with HIV (PLHIV) are failing treatment without HIV drug resistance in the drug target region. While sub-optimal adherence is likely the cause of treatment failure in many PLHIV, resistance emerging at non-canonical (HIV drug resistance mutations occurring outside the drug target site) drug target site sites is also plausible. Non-canonical drug resistance mechanisms have been identified for integrase strand transfer inhibitors (INSTIs), protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and NRTIs. Overall, they may act by i) restoring viral fitness caused by mutations in the drug target sites, ii) enhance resistance when occurring with mutations at the drug target sites iii) independently cause resistance even in the absence of drug resistant mutations (DRMs) at the drug target site iv) prime the emergence of resistant variants with DRMs at drug target sites. However, the clinical relevance of non-canonical resistance mechanism beyond in vitro and small in vivo studies is still needed and could include the assessment of such mechanisms in clinical trials and implementation studies. This information would be vital in guiding effective management of PLHIV with viral non-suppression despite good adherence as well as informing public health surveillance strategies.