JAIDS Journal of Acquired Immune Deficiency Syndromes最新文献

Background: Raltegravir is an HIV integrase strand transfer inhibitor recommended for use in pregnancy. The aim of this study was to assess risk of birth defects and other suboptimal outcomes after prenatal exposure to raltegravir.

Methods: We used pooled, prospectively collected individual patient data from studies in the European Pregnancy and Paediatric Infections Cohort Collaboration. Pregnancies with any prenatal exposure to raltegravir with outcomes in 2008-2020 were included. Birth defects were classified according to World Health Organization's International Classification of Diseases and EUROCAT criteria. Earliest prenatal exposure timing was classified as periconception [exposure at ≤6 completed gestational weeks (GWs)], later first trimester (T1) (exposure in T1 at >6 completed GWs), and second/third trimester (exposure at >12 completed GWs).

Results: A total of 1499 pregnancies across 9 cohorts were included. Where timing was available (n = 1449), earliest raltegravir exposure was in the periconception period for 505 (34.8%), later T1 in 65 (4.5%), and T2/T3 in 879 (60.7%). The overall prevalence of birth defects among live-born infants with prenatal raltegravir exposure was 3.9% (95% confidence interval: 2.9, 5.0) (1443/1466) (International Classification of Diseases), with no increased risk observed for those exposed in the periconception period ( P = 0.290). Among singleton live-born infants, 11.9% (160/1346) were born preterm, 11.3% (148/1307) low birthweight, and 8.6% (111/1291) small for gestational age, with no difference in outcomes observed by timing of raltegravir exposure.

Conclusions: These findings add to the evidence base around safety of raltegravir use in pregnancy, although ongoing safety monitoring is needed to rule out risk of rare outcomes.

Introduction: HIV/AIDS continues to be a significant health issue in sub-Saharan Africa, with stigma likely affecting ART adherence, and subsequently viremia, inflammation, and cardiovascular disease (CVD). We investigated the association between stigma, ART adherence, and CVD risk among people living with HIV (PLWH).

Setting: A longitudinal study was conducted among 325 PLWH from the Ndlovu Cohort Study, South Africa.

Methods: Stigma was assessed using a 12-item questionnaire (range: 0-44; higher scores indicate greater stigma). Pulse wave velocity (PWV, CVD surrogate marker) and viral load (VL) were assessed at 12 and 36 months. VL was considered a surrogate marker of ART adherence: VL > 1000 copies indicating poor/no adherence, VL 50-1000 copies suboptimal, and VL < 50 copies good adherence. The relationship between stigma, VL, and PWV was assessed by linear regression and changes in PWV overtime by mixed linear models.

Results: At baseline, PLWH (n = 325, mean age (SD) = 41.1 (10.2) years, 67% female) had mean PWV of 7.3 min/s. Good, suboptimal, and poor adherence were 78%, 15%, and 7%, respectively. The mean (SD) stigma score was 16.9 (1.4) and was not associated with VL and PWV. Suboptimal and poor adherence were associated with higher PWV [beta = 4.18 (95% confidence interval (CI): 1.79 to 6.57)] at 12 months and between 12 and 36 months [beta = 1.30 (95% CI: 0.06 to 2.55)] in mixed model analyses in PLWH older than 49 years, respectively. PWV increased by 0.21 min/s (95% CI: 0.02 to 0.40; P = 0.03) between 12 and 36 months overall.

Conclusions: In this study, poor ART adherence was associated with higher PWV. The stigma score was low and not associated with ART adherence and PWV.

Background: Daily oral pre-exposure prophylaxis (PrEP) use among gay, bisexual, and other men who have sex with men (GBMSM) remains suboptimal. Assessing behavioral readiness for PrEP use among GBMSM who can benefit and offering PrEP may increase uptake among GBMSM. We measured 4-item readiness for taking PrEP among GBMSM who have not been offered PrEP by a provider.

Methods: GBMSM in Atlanta, Chicago, and Raleigh-Durham reporting recent condomless anal sex were assessed for "readiness" to discuss PrEP with a provider, test for HIV, take a daily pill, attend provider appointments, and a 4-component composite score for PrEP readiness. χ 2 tests and multivariable logistic regression were applied to examine factors associated with readiness to use PrEP.

Results: Study sample (n = 187) was 51% Black/African American, 15% Hispanic/Latino, 30% identified as bisexual or straight or other, and 29% had no health insurance. In total, 55% said they were ready to discuss PrEP with a provider, 88% were ready to get an HIV test, 45% were ready to take a daily pill, 48% were ready to attend appointments, and 37% reported overall PrEP readiness. Having no health insurance was associated with readiness for a daily pill [adjusted odds ratio (AOR) = 2.78, confidence interval (CI) = 1.34-5.78] and 4-item PrEP readiness (AOR = 2.34, CI = 1.13-4.85). Self-identification as gay (vs bisexual/straight) was associated with readiness to discuss PrEP (AOR = 2.14, CI = 1.05-4.36).

Conclusions: Only 37% of GBMSM with recent condomless anal sex were ready for PrEP based on the 4-item readiness. Readiness may differ based on sexual identity, insurance status, and other characteristics. Efforts are needed to increase readiness across behavioral components of PrEP use.

Background: The effectiveness of pre-exposure prophylaxis (PrEP) in preventing HIV depends on consistent use, particularly during periods of increased risk. Depression, which disproportionately affects gay, bisexual, and other men who have sex with men (GBMSM), may hinder sustained PrEP engagement. This study examines how depression impacts consistent PrEP use among GBMSM in the first 18 months after initiating oral PrEP.

Methods: We analyzed electronic health records for adult GBMSM prescribed oral PrEP between January 2015 and February 2022 at three clinics in Boston, MA. Participants were followed for 18 months after initial prescriptions, tracking three outcomes: temporary prescription gaps (interruptions in received prescriptions), dropping out of current PrEP care (cessation of prescriptions) and HIV seroconversion. Associations between baseline depression diagnosis and these outcomes were estimated using subdistribution and cause-specific Cox proportional hazards regression models.

Results: Among 8,077 GBMSM prescribed oral PrEP, 19% had a baseline depression diagnosis. Of these, 41% experienced gaps, 38% dropped out, and 0.4% seroconverted without a prior gap. Depression was modestly associated with higher rates of PrEP disruptions (Prescription gaps: Adjusted hazard ratio [aHR] 1.10 [95% CI: 1.00, 1.20]; Dropping out: aHR 1.16 [95% CI: 1.05, 1.28]) after adjusting for age, race/ethnicity, urbanicity, high-risk sexual behavior, poverty, and bacterial STI diagnoses. However, it did not significantly impact the cumulative incidence of PrEP interruptions.

Conclusions: Although depression's impact on PrEP use was modest, integrating mental health care into PrEP programs remains essential for improving engagement and supporting sustained use among GBMSM.

Background: We assessed annual out-of-pocket (OOP) costs for HIV preexposure prophylaxis (PrEP)-related services among commercially insured individuals in the U.S. before and after the Affordable Care Act (ACA) mandated no cost-sharing in 2021.

Methods: Using data from a large commercial database, we identified persons aged ≥18 years who were prescribed PrEP from 2017-2022. Medical claims for PrEP-related services submitted within one week before each PrEP prescription were extracted using CPT codes. For each service, we calculated the annual proportion of persons incurring OOP costs and associated annual amounts, adjusted to 2022 U.S. dollars. We assessed trends in the proportion of persons with OOP costs for each service from 2019-2022. We also examined the association between OOP cost occurrence and patient demographic characteristics.

Results: Among 141,300 PrEP users, we observed decreasing trends in the proportion incurring OOP costs for PrEP ancillary services over the study period. In 2022, OOP costs were incurred by 65.6% for provider visits, 14.3% for HIV testing, and 32.5% for creatinine testing, with mean OOP costs of $54.18, $26.06, and $6.07, respectively. Rural users were more likely to incur costs than urban users.

Conclusions: Despite ACA mandates, many persons received cost-sharing bills for PrEP services. Standardized billing and coding, along with enhanced monitoring and enforcement, could help protect access to evidence-based preventive care.

Introduction: Evidence is needed to inform differentiated service delivery models for people with HIV (PWH). During the COVID-19 pandemic, South Africa temporarily changed the validity of repeat prescriptions for ART from 6 to 12 months. We evaluated the association between these changes and HIV viral non-suppression in the private health sector.

Methods: We analysed routine claims data from a large private-sector HIV management programme. PWH aged >15 years from 4 months after first ART evidence were included. We conducted an interrupted time-series analysis comparing trends in the proportions of PWH with viral non-suppression (viral load ≥50 copies/mL) during three periods: January 1, 2019 to April 23, 2020 (conventional 6-monthly script renewal); April 24, 2020 to September 25, 2021 (12-monthly renewal); and September 26, 2021 to November 30, 2022 (6-monthly renewal re-instated). We used weighting to maintain the age, sex, ART regimen and medical scheme distributions of our study population over time.

Results: Monthly odds of viral non-suppression initially decreased by 4% per annum (adjusted odds ratio (aOR) 0.96, 95% confidence interval (CI) 0.93-0.99). During 12-monthly renewal, there were steeper declines of 11% per annum (aOR 0.89, 95% CI 0.87-0.91). After 6-monthly renewal was re-introduced, viral non-suppression instead increased by 6% per annum (aOR 1.06 95% CI 1.03-1.09). Changes in slopes were significant (p-values <0.001).

Conclusion: Measures implemented during COVID-19 to ensure continued access to chronic medication provided unique evidence for models involving less frequent clinical visits. Extending prescription renewal periods was not associated with worse virologic outcomes among privately-insured PWH.

Background: Mutations conferring resistance to HIV Integrase Strand Transfer Inhibitors (INSTI) can occur outside integrase, including in env gp41, in vitro, but it remains unclear whether these arise under INSTI selection in vivo.

Methods: Using a large database of clinically-derived HIV sequences linked to antiretroviral treatment histories, we sought to identify mutations in gp41 associated with INSTI exposure by comparing integrase and gp41 amino acid frequencies in INSTI-naïve versus INSTI-treated individuals. Gp41 was investigated because this region is routinely sequenced to assess fusion inhibitor resistance.

Results: We identified 72 individuals with subtype B HIV for whom a genotypic INSTI resistance test performed after ≥3 months of INSTI exposure revealed susceptibility to all INSTIs (HIVdb v8.8; score<15), and for whom plasma INSTI concentrations were detectable by mass spectrometry. Gp41 sequencing was successful for 52 (72%) of these. The median INSTI exposure duration in this group was 20 (Q1-Q3:10-39) months, with raltegravir (>54%), dolutegravir (52%) and elvitegravir (23%) being the most frequently prescribed. Comparison of gp41 amino acid frequencies between this group and a comparison group of 1221 gp41 sequences from INSTI- naïve individuals using Fisher's exact test with Benjamini-Hochberg correction for multiple comparisons identified the gp41 substitution V182I (OR=3.75, p=2.2x10-4, q=0.01) as over-represented among INSTI-treated persons. When comparing gp41 sequences pre- and post-INSTI therapy in this group however, no evidence of INSTI-driven selection was observed at this position.

Conclusion: While off-target INSTI substitutions may arise in vivo, there is currently insufficient evidence to recommend expanding INSTI resistance testing to include Env.

Background: Men who have sex with men (MSM) with HIV are disproportionately affected by human papillomavirus (HPV) and related diseases. We assessed HPV vaccine effectiveness (VE) against anal HPV among MSM with HIV.

Methods: During 2018-2023, residual anal specimens from MSM with HIV, aged 18-45 years, attending sexual health clinics in three U.S. cities were collected and tested for HPV. Demographic and vaccination information were obtained from clinic records or immunization registries. Timing of vaccination relative to HIV acquisition was unknown. Log-binomial regression was used to calculate adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) for associations between vaccination (≥1 dose) and quadrivalent vaccine (4vHPV)-type infection, adjusting for city. Models were stratified by age group (18-26, 27-45 years). VE was calculated as (1-aPR) x 100.

Results: Among 224 persons aged 18-26 years, 54% were vaccinated. Compared with unvaccinated persons, 4vHPV-type prevalence was lower in those vaccinated at age <18 (aPR=0.31, 95% CI:0.14-0.72, VE=69%) and ≥2 years before specimen collection (aPR=0.54, 95% CI:0.31-0.92, VE=46%). Among 700 persons aged 27-45 years, 17% were vaccinated. Compared with unvaccinated persons, 4vHPV-type prevalence was lower in those vaccinated at ages 18-26 (aPR=0.63, 95% CI:0.45-0.89, VE=37%) and ≥2 years before specimen collection (aPR=0.63, 95% CI:0.46-0.86, VE=37%).

Conclusions: While timing of vaccination relative to HIV acquisition was unknown, we found significant VE against prevalent HPV infection in adult MSM with HIV. Within each age group, VE was higher with younger age at vaccination.

Background: Myosteatosis affects muscle strength and mobility function, and further is associated with inflammation, yet there is limited work examining the effects of exercise training in people with HIV (PWH).

Methods: We conducted a randomized trial of 16-weeks aerobic exercise and resistance training (AEX+RT) compared to standard of care control in PWH ≥50 years of age. Muscle area, intramuscular adipose tissue (IMAT), and muscle density (Hounsfield units) of the mid-thigh was determined by computed tomography. Inflammatory markers included IL-6, hsCRP, TNF-α, and IL-18.

Results: Among participants randomized to AEX+RT (N=17) or control (N=16), the mean (SD) age was 60.1(6.7) years, and the majority identified as black (70%) and men (91%). Significant between-group differences were found for muscle area (+7.5% vs. -3.1%, p<0.01), muscle density (+5.2% vs. -0.3%, p<0.01), and leg strength (+51.8% vs. +1.3%, (p<0.001). The decrease in IMAT after AEX+RT did not reach significance (-6.7%, p=0.07). There was no change in body weight or abdominal adiposity. At baseline, muscle density significantly correlated inversely with TNF-α and IL-6. There was a significant correlation between IMAT and inflammatory markers except IL-18. There were no significant between-group differences in changes in inflammatory markers. Percent change in inflammatory measures did not correlate with change in muscle measures.

Conclusion: Combined AEX+RT increased thigh muscle density, size, and strength in older PWH. Baseline association of muscle density and IMAT with inflammation underscores the need for further work in larger, more diverse populations to target underlying mechanisms for improvements in muscle quality in PWH.