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Objective: People with HIV on ART are highly vulnerable to non-AIDS-related comorbidities, including HIV-associated neurocognitive disorders, which are linked to persistently activated monocytes/macrophages. Smoking is a major contributor to HIV-related comorbidities. However, nicotine alone has anti-inflammatory effects, mainly through α7-nicotinic receptor (nAChR) activation. Galantamine (GAL) is an FDA-approved pro-cognitive medication that increases endogenous acetylcholine and also directly potentiates the α7-nAChR. We hypothesized that GAL would improve neurocognition in PWH, both by direct pro-cognitive effects and by reducing inflammation. We also explored whether effects differed by smoking status.

Design/methods: Smoking and nonsmoking PWH/ART participated in a double-blind, randomized, placebo-controlled crossover study of 12 weeks of GAL treatment. Primary outcomes were composite neurocognitive test score; monocyte CD16, CD163 and CCR2, and CD8 T-cell CD38/HLA-DR; and plasma sCD16, sCD163 and CCL2. Plasma hsCRP and neurofilament light chain (NFL) were also measured. Exploratory analyses included plasma mediators by Luminex and monocyte transcriptome by RNAseq.

Results: Neurocognition did not differ between GAL and placebo treatment (adjusted standardized difference (95% CI) -0.02 (-0.2, 0.2); p = 0.82), with no difference by smoking status (p = 0.51). Monocyte CCR2 expression was 15.2% (5, 25.1) greater with GAL than placebo (p = 0.006). No differences were seen in monocyte CD16 (p = 0.76) or CD163 (p = 0.8), CD8 T-cell CD38/HLA-DR (p = 0.54), or plasma sCD163 (p = 0.36), sCD14 (p = 0.46), or CCL2 (p = 0.34). NFL and hsCRP were not different, but several pro-inflammatory cytokines increased with GAL. Only modest effects were seen on monocyte gene expression.

Conclusions: Galantamine for 12 weeks did not improve cognition or reduce inflammation in PWH/ART regardless of smoking status.

Introduction: To ensure the safe use of preexposure prophylaxis (PrEP) for HIV prevention, the Centers for Disease Control and Prevention (CDC) recommends laboratory testing with specific tests for all individuals before PrEP initiation.

Methods: We analyzed the Merative™ MarketScan® commercial insurance database to assess the use of laboratory testing for HIV antigen/antibody (Ag/Ab), HIV RNA tests, sexually transmitted infection, Hepatitis B virus infection, and other CDC-recommended testing for persons who initiated PrEP during 2022-2023. We estimated testing rates for each laboratory assay based on its specific recommendation at the time of PrEP initiation, which was defined as the interval extending from 14 days prior to through 14 days following the recorded initiation date.

Results: Among 38,855 persons who initiated PrEP during 2022-2023, only 35.3% had a documented laboratory-based HIV Ag/Ab test during the ± 14-day period. Among 757 injectable PrEP users, only 35.4% were tested for HIV RNA during the ± 14-day period. Testing rates of other recommended laboratory tests were also low. Persons who were prescribed oral PrEP, who reside in the South and in non-metropolitan areas had lower testing rates for all laboratory tests.

Conclusions: CDC-recommended laboratory testing was suboptimal at PrEP initiation. Some PrEP users might have been tested for HIV by using only a point-of-care (POC) test to facilitate rapid PrEP initiation despite a recommendation to confirm with a laboratory-based test. Implementation of clinical decision supports with laboratory order sets tailored to each type of PrEP medication could increase adherence to CDC-recommended laboratory testing at PrEP initiation.

Objective: This study aimed to assess the burden, severity, and pattern of Coronary artery disease (CAD) in people with HIV (PWH), as well as its relationship with metabolic syndrome, inflammation, and endothelial dysfunction.

Design: Cross-sectional study.

Methods: A comparative cross-sectional study was conducted on 72 PWH and 72 matched people without HIV at Aminu Kano Teaching Hospital (AKTH). Data collection included demographics, metabolic parameters, viral load, brachial artery flow-mediated dilation (BAFMD) assessed via ultrasound, and coronary artery calcification (CAC) scores obtained using electrocardiogram (ECG)-gated computed tomography. CAD predictors were analysed using t-tests, linear regression, and Chi-squared/Fisher's exact tests (p ≤ 0.05).

Results: Among 144 participants (72 PWH, 72 controls), PWH had higher CAD prevalence (31.9% vs. 4.2%, p < 0.001) and mean CAC scores (23.2 vs. 2.7, p < 0.001). CAD was significantly associated with longer ART duration (p = 0.04), higher BMI (p = 0.005), and reduced BAFMD (p = 0.020). In controls, hsCRP predicted CAD (p = 0.004).

Conclusion: PWH in northern Nigeria have a higher burden of CAD compared to HIV negative controls, with greater CAC and endothelial dysfunction, independent of viral load status. These findings highlight the need for routine cardiovascular screening and CVD prevention integration into HIV care.

Objectives: Despite longer life expectancies, those aging with HIV experience increased comorbidity and other health challenges relative to the general population. Alterations in the composition of the gut microbiome are associated with increased immune activation and aging, but few studies have explored the association of the gut microbiome with adverse age-related outcomes in people living with HIV. We assessed the relationship between gut microbiome composition and healthy aging in HIV.

Design/methods: The CHANGE HIV study is a Canadian cohort of people aged 65 and older, which aims to investigate correlates of healthy aging in HIV. Rectal swabs were collected at enrolment from a subset of 158 consenting participants, which we analyzed with 16S rRNA gene sequencing to characterize the gut microbiome. Healthy aging was quantified using the Rotterdam Healthy Aging Score (HAS) and categorized as healthy (13-14), intermediate (11-12), and poor (0-10). We collected other markers of healthy aging including cognition, frailty, and demographics.

Results: Gut microbiome diversity did not differ based on HAS category, although some disease-associated bacteria were enriched in participants with lower HAS. Gut microbiome diversity did not differ based on age or frailty status. Lower HAS score group was associated with lower household income, poorer nutrition and cognition, and earlier year of HIV infection.

Conclusion: Gut microbiome composition was not associated with healthy aging as defined by the HAS, although there were weak associations between HAS and disease-associated bacterial genera. Interventions that target social circumstances may provide greater improvements in health among aging persons with HIV.

Objective: Examine the proportion of people with HIV engaging in behaviours associated with hepatitis C virus (HCV) infection after successful direct-acting antiviral (DAA) treatment and establish longitudinal patterns of behavioural risk over time.

Design: Multinational, prospective cohort study (International Collaboration on Hepatitis C Elimination in HIV Cohorts).

Methods: Individuals with HIV successfully treated with DAAs and ≥2 follow-up visits with behavioural data were included. Changes in the proportion of any risk behaviour after treatment, which included sexual and drug use behaviours, were analysed using logistic regression with generalized estimating equations. We identified distinct trajectories of any risk behaviour over time using group-based trajectory models (GBTM).

Results: Of the 1,477 individuals included, 487 (33.0%) were people who inject drugs, 378 (25.6%) were men who have sex with men and 442 (29.9%) were both. During a median 2.7 years (IQR=1.6-3.9) of follow-up, the proportion engaging in any risk behaviour slightly decreased over time (adjusted odds ratio per half year=0.97, 95% confidence interval=0.95-0.99). GBTM revealed four distinct behavioural trajectories: consistently low (n=433, 29.3% of total population), moderate at baseline and increasing (n = 119, 8.1%), high at baseline and decreasing (n = 184, 12.5%) and consistently high (n = 741, 50.2%).

Conclusions: Despite slight decreases in behaviours following successful DAA treatment, half of individuals had a consistently high probability of behaviours that put them at risk of HCV reinfection over time. As reinfections comprise a growing proportion of new incident HCV cases, these findings underscore the importance of ongoing primary prevention measures alongside testing and retreatment to eliminate HCV.

Objective: To compare Antiretroviral Therapy (ART) utilization and adherence before and after expansion of a drug coverage program.

Methods: A retrospective study was conducted using administrative databases in Saskatchewan, Canada. Beneficiaries with at least one diagnostic claim for HIV infection or AIDS between 1999 and 2021 were eligible. An interrupted time series analysis described trends for three indicators of ART utilization before and after drug coverage expansion in 2018: number of active users (defined by at least one ART claim), number of ART claims, and ART spending. A random-effects logistic regression model, controlling for confounders, was used to evaluate the likelihood of achieving at least 95% adherence measured by the proportion of days covered (PDC) before versus after coverage expansion.

Results: A total of 519 individuals received at least one ART claim during the study period and met all other inclusion criteria. Time series models detected statistically significant increases in the number of active ART users and ART claims within four months following coverage implementation. Corresponding increases in ART spending were offset by decreases over prior years. No statistically significant changes were detected in the likelihood of achieving at least 95% PDC between the pre- versus post-coverage periods (adjusted OR 1.26, 95% CI: 0.71 to 2.25, p = 0.423).

Conclusion: ART coverage expansion was associated with a higher number of claims, more active users, and a change in spending pattern; however, we did not detect a difference in the likelihood of achieving optimal adherence. Addressing additional gaps in HIV management remains a priority.

Objective: Inequalities in the antiretroviral therapy (ART) cascade across subpopulations remain an ongoing challenge in the global HIV response. Eswatini achieved the UNAIDS 95-95-95 ART cascade targets by 2020, with differentiated programs to minimize inequalities across subpopulations, including for female sex workers (FSW) and their clients. We sought to estimate the impacts of this achievement, through a retrospective impact evaluation of ART scale-up in Eswatini.

Design: Drawing on population-level and FSW-specific surveys, we developed a compartmental model of heterosexual HIV transmission, and calibrated it to observed HIV prevalence, incidence, and ART cascade scale-up in Eswatini.

Methods: We defined four counterfactual scenarios in which the population overall reached only 80-80-90 by 2020, but where FSW, clients, both, or neither were disproportionately left behind, reaching only 60-40-80. We estimated additional HIV infections by 2020 in counterfactual vs observed scenarios, and identified epidemic conditions which maximized differences.

Results: Compared with observed cascade scale-up in Eswatini, leaving behind neither FSW nor their clients led to median (95% CI) 8.8 (6.3, 10.9)% additional infections by 2020 vs 14.3 (10.8, 18.6)% if both were left behind - a 63 (31, 128)% increase. The impact of leaving behind FSW and/or clients was largely determined by their population sizes and HIV incidence ratio among clients vs men overall.

Conclusions: Inequalities in the ART cascade across subpopulations can undermine the anticipated prevention impacts of cascade scale-up. As Eswatini has shown, addressing inequalities in the ART cascade that intersect with transmission risk can maximize incidence reductions from cascade scale-up.

Background: There is limited evidence concerning the relationship between cardiometabolic characteristics and health-related quality of life (HRQoL), and potential effects of statin therapy among people with HIV (PWH).

Methods: The Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) enrolled PWH aged 40-75 years on antiretroviral therapy (ART) with low-to-moderate ASCVD risk. Coronary computed tomography angiography assessed coronary plaque among a subset of participants in the REPRIEVE Mechanistic Substudy at baseline and 24 months. The Short Form-36-Item Health Survey Version 2 was collected at baseline, and physical (PCS) and mental (MCS) component summary scores were determined. We explored the relationship of PCS and MCS with cardiometabolic characteristics, coronary atherosclerosis, and assessed change in score by treatment group (pitavastatin vs. placebo).

Results: Of 733 participants, median age was 51 years, 84% were male, 34% were Black non-Hispanic, and median years diagnosed with HIV was 15. At baseline, for participants randomized to pitavastatin vs. placebo the median PCS was 54.5 (Q1,Q3: 46.9, 57.7) vs. 54.1 (47.5, 58.0), and the median MCS was 52.9 (44.1, 57.6) vs. 52.8 (44.0, 57.9). In fully adjusted analyses, older age, Black non-Hispanic race/ethnicity, ART regimen class, elevated BMI, and cigarette smoking were associated with lower PCS. No clear trends were apparent with MCS. Between baseline and month 24, declines in PCS and MCS were minimal with no apparent difference by treatment group.

Conclusions: Among this cohort of ART-treated PWH, baseline cardiometabolic risk factors were associated with worse self-reported physical HRQoL, with no apparent effect of statin therapy.

Trial registration: REPRIEVE; NCT02344290; https://clinicaltrials.gov/study/NCT02344290.

Objective: To compare HIV incidence among female sex workers (FSW) and single mothers, and to determine the factors associated with seroconversion among both populations.

Design: Prospective cohort conducted in Lusaka and Ndola, Zambia between 2012 and 2022.

Methods: Study staff recruited FSW from common sex work locales and recruited single mothers from postnatal infant vaccination clinics. Enrolled participants were HIV-negative, aged 18-45, and identified as either a FSW or single mother. We measured HIV incidence and assessed associated factors using Poisson regression with adjusted rate ratios (aRRs) and 95% confidence intervals (CIs).

Results: The study enrolled 2,539 women (1,533 FSW and 1,006 single mothers). HIV incidence was not statistically different for FSW (3.24 per 100 person-years;95%CI:2.63-3.95) and single mothers (2.64 per 100 person-years;95%CI:2.00-3.43). Factors associated with HIV seroconversion were positive syphilis (aRR:2.03;95%CI:1.46-2.83) and trichomonas (aRR:1.48;95%CI:1.06-2.06) diagnoses, inconsistent condom use (aRR:1.60;95%CI:1.06-2.40), and greater than 6months follow-up time in the study (aRR:2.45;95%CI:1.52-3.94).

Conclusions: Single mothers share similar HIV risk to FSW, and both populations require targeted interventions. For single mothers, government postnatal clinics should combine comprehensive sexual education with screening and treatment for syphilis and trichomoniasis. For FSW, we recommend integrated and accessible interventions to prevent HIV and sexually transmitted infections. Future studies should investigate the social determinants of condom use among both FSW and single mothers.

Objective: To characterize all-cause unplanned 30-day readmissions among adults with chronic kidney disease (CKD) of all-stages by HIV status in the US.

Design: Retrospective cohort study using the Nationwide Readmissions Database-an all-payer nationally representative database.

Methods: Index (i.e. initial) admissions and readmissions were defined following the U.S. Centers for Medicare & Medicaid Services (CMS) guidelines. We evaluated trends in the readmission risk among adults by CKD and HIV status during 2016-2022 and compared the overall and subgroup-specific readmission risk by HIV status among adults with CKD in 2022. Crude and age- and sex-adjusted risk ratios (aRR) were calculated using average marginal estimates from mixed-effect logistic regressions. Survey weights were applied.

Results: Among people with CKD, the readmission risk declined from 33.4% in 2016 to 29.1% in 2022 for people with HIV (PWH) and declined from 23.7% in 2016 to 21.9% in 2022 for people without HIV (PWoH). In 2022, there were 43,087 index admissions from PWH and 5,170,351 from PWoH. PWH were more likely to be male, younger, have end-stage CKD, and reside in low-income areas versus PWoH. For both PWH and PWoH, the readmission risk increased with more advanced CKD stages but decreased with older age. In 2022, PWH were more likely to be readmitted than PWoH (aRR = 1.20[95%CI:1.17,1.23]). This disparity was greater among those <40 years (aRR = 1.32[95%CI:1.23,1.42]).

Conclusions: More efforts are needed to mitigate the excessive readmission of people with CKD. PWH, especially young individuals, could represent a critical group for intensified intervention in CKD readmission prevention programs.