Transitions Between Preexposure Prophylaxis Eligibility States and HIV Infection in the Lisbon Cohort of HIV-Negative Men Who Have Sex With Men: A Multistate Model Analysis

We aimed to describe transitions between preexposure prophylaxis (PrEP) eligibility and human immunodeficiency virus (HIV) infection among HIV-negative men who have sex with men (MSM). We used data from 1,885 MSM, who had not used PrEP, enrolled in the Lisbon Cohort of MSM, with at least 2 consecutive measurements of PrEP eligibility from 2014–2020. A time-homogeneous Markov multistate model was applied to describe the transitions between states of PrEP eligibility—eligible and ineligible—and from these to HIV infection (HIV). The intensities of the transitions were closer for ineligible-to-eligible and eligible-to-ineligible transitions (intensity ratio, 1.107, 95% confidence interval (CI): 1.080, 1.176), while the intensity of the eligible-to-HIV transition was higher than that for ineligible-to–HIV transition (intensity ratio, 9.558, 95% CI: 0.738, 65.048). The probabilities of transitions increased with time; for 90 days, the probabilities were similar for the ineligible-to-eligible and eligible-to-ineligible transitions (0.285 (95% CI: 0.252, 0.319) vs. 0.258 (95% CI: 0.228, 0.287)), while the eligible-to-HIV transition was more likely than ineligible-to-HIV (0.004 (95% CI: 0.003, 0.007) vs. 0.001 (95% CI: 0.001, 0.008)) but tended to become closer with time. Being classified as ineligible was a short-term indicator of a lower probability of acquiring HIV. Once an individual moved to eligible, he was at a higher risk of seroconversion, demanding a timely delivery of PrEP.This work was supported by national funds of Fundação para a Ciência e Tecnologia (FCT), under the scope of the project UIDB/04750/2020—Research Unit of Epidemiology–Institute of Public Health of the University of Porto (EPIUnit). P.M. was the recipient of doctoral grant SFRH/BD/112867/2015, co-funded by the FCT and the Programa Operacional Capital Humano/Fundo Social Europeu. C.M. was supported by Portuguese funds through FCT within the Project UID/MAT/00013/2013

Self-reported body fat change in HIV-infected men is a marker of decline in physical health-related quality of life with aging, independent of co-morbidity

Objective: Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown. Design: This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later. Methods: Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixedmodel regression. Results: We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time. Conclusions: Negative self-perceived body fat changes were associated with decline in physical health related quality of life, independent of comorbidities, and may be a marker of an increased risk for physical function decline with aging

Loneliness and Frailty Among Middle-Aged and Aging Sexual Minority Men Living With or Without HIV: A Longitudinal Cross-Lagged Panel Analysis

Background and Objectives Loneliness is associated with frailty among older adults (60+), and there is evidence suggesting that this association may be bidirectional. However, there is limited evidence of this relationship over time among middle-aged and aging sexual minority men. We explored the bidirectional relationship between loneliness and frailty over 2 years among sexual minority men living with or without human immunodeficiency virus (HIV) from the Healthy Aging substudy of the Multicenter AIDS Cohort Study. Research Design and Methods We used data from 1 118 men (561 living with HIV; 557 living without HIV) aged 40 years or older with measurement of frailty or loneliness at Times 1 (September 2016 to March 2017) and 2 (September 2018 to March 2019). Descriptive statistics were generated. We used autoregressive cross-lagged panel analysis to examine the bidirectional association between frailty and loneliness at both time points while adjusting for time-stable and time-dependent covariates at Time 1. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were generated. Results The estimated prevalence of loneliness at both time points was 35.5%. The estimated prevalence of frailty at Times 1 and 2 were 7.8% and 12.1%, respectively. Participants reporting loneliness at Time 1 had greater odds of being frail at Time 2 (aOR = 2.14; 95% CI: 1.23–3.73). Frailty at Time 1 was not associated with loneliness at Time 2 (aOR = 1.00; 95% CI: .44–2.25). The autoregressive effects of frailty (aOR = 23.43; 95% CI: 11.94–46) and loneliness (aOR = 13.94; 95% CI: 9.42–20.61) were large. Discussion and Implications Men who felt lonely had higher odds of being frail 2 years later while the reciprocal association was not shown. This suggests that loneliness preceded frailty and not the other way around. Early and frequent assessments of loneliness may present opportunities for interventions that minimize the risk of frailty among sexual minority men living with and without HIV.This was supported by the National Institute on Minority Health and Health Disparities (grant number R01 MD010680; M.R.F. and M.P.) and the National Institute on Drug Abuse (grant number K01DA047912). The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). MACS/WIHS Combined Cohort Study (MWCCS) (Principal Investigators): Atlanta Clinical Research Site (CRS) (Ighovwerha Ofotokun, Anandi Sheth, and Gina Wingood), U01-HL146241; Baltimore CRS (Todd Brown and Joseph Margolick), U01-HL146201; Bronx CRS (Kathryn Anastos and Anjali Sharma), U01-HL146204; Brooklyn CRS (Deborah Gustafson and Tracey Wilson), U01-HL146202; Data Analysis and Coordination Center (Gypsyamber D’Souza, Stephen Gange, and Elizabeth Golub), U01-HL146193; Chicago–Cook County CRS (Mardge Cohen and Audrey French), U01-HL146245; Chicago-Northwestern CRS (Steven Wolinsky), U01-HL146240; Connie Wofsy Women’s HIV Study, Northern California CRS (Bradley Aouizerat, Phyllis Tien, and Jennifer Price), U01-HL146242; Los Angeles CRS (Roger Detels), U01-HL146333; Metropolitan Washington CRS (Seble Kassaye and Daniel Merenstein), U01-HL146205; Miami CRS (Maria Alcaide, Margaret Fischl, and Deborah Jones), U01-HL146203; Pittsburgh CRS (Jeremy Martinson and Charles Rinaldo), U01-HL146208; UAB-MS CRS (Mirjam-Colette Kempf, Jodie Dionne-Odom, and Deborah Konkle-Parker), U01-HL146192; and UNC CRS (Adaora Adimora), U01-HL146194. The MWCCS is funded primarily by the National Heart, Lung, and Blood Institute, with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute on Aging, National Institute of Dental and Craniofacial Research, National Institute of Allergy and Infectious Diseases, National Institute of Neurological Disorders and Stroke, National Institute of Mental Health, National Institute on Drug Abuse, National Institute of Nursing Research, National Cancer Institute, National Institute on Alcohol Abuse and Alcoholism, National Institute on Deafness and Other Communication Disorders, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute on Minority Health and Health Disparities, and in coordination and alignment with the research priorities of the NIH, Office of AIDS Research. MWCCS data collection is also supported by UL1-TR000004 (University of California, San Francisco Clinical and Translational Science Award), P30-AI-050409 (Atlanta Center for AIDS Research [CFAR]), P30-AI-050410 (UNC CFAR), and P30-AI-027767 (University of Alabama CFAR). This work was also supported by national funds through the FCT–Foundation for Science and Technology, I.P., within the scope of projects UIDB/04750/2020 and LA/P/0064/2020. This study was also supported by a Scientific Employment Stimulus contract to A.H. (CEECIND/01793/2017)

Prevalence and 1-year incidence of frailty among women with and without HIV in the Women's Interagency HIV Study

A previous cross-sectional analysis of 2028 women in the Women’s Interagency HIV Study (WIHS), who were on average 39 years old, found a frailty prevalence of 17% and 10% in women with or at risk for HIV, respectively [1]. To our knowledge, the only two longitudinal studies of frailty among people with HIV were conducted in the Multicenter AIDS Cohort Study (MACS), which includes only men [2,3]. Data on the distribution of frailty components are limited, and have not been reported for HIV-seropositive people in the United State

Speech audiometry findings from HIV+ and HIV− adults in the MACS and WIHS longitudinal cohort studies

The purpose of this study was to compare various speech audiometry measures between HIV+ and HIV− adults and to further evaluate the association between speech audiometry and HIV disease variables in HIV+ adults only. Three hundred ninety-six adults from the Multicenter AIDS Cohort Study (MACS) and Women’s Interagency HIV Study (WIHS) completed speech audiometry testing. There were 262 men, of whom 117 (44.7%) were HIV+, and 134 women, of whom 105 (78.4%) were HIV+. Speech audiometry was conducted as part of the standard clinical audiological evaluation that included otoscopy, tympanometry, and pure-tone air- and bone-conduction thresholds. Specific speech audiometry measures included speech recognition thresholds (SRT) and word recognition scores in quiet presented at 40 dB sensation level (SL) in reference to the SRT. SRT data were categorized in 5-dB steps from 0 to 25 dB hearing level (HL) with one category as ≥30 dB HL while word recognition scores were categorized as <90%, 90–99%, and 100%. A generalized estimating equations model was used to evaluate the association between HIV status and both ordinal outcomes. The SRT distributions across HIV+ and HIV− adults were similar. HIV+ and HIV− adults had a similar percentages of word recognition scores <90%, a lower percentage of HIV− adults had 90–99%, but HIV− adults had a higher percentage of 100%. After adjusting for covariables, HIV+ adults were borderline significantly more likely to have a higher SRT than HIV− adults (odds ratio [OR] = 1.45, p = 0.06). Among HIV+ adults, HIV-related variables (i.e., CD4+ T-cell counts, HIV viral load, and ever history of clinical AIDS) were not significantly associated with either SRT or word recognition score data. There was, however, a ceiling effect for word recognition scores, probably the result of obtaining this measure in quiet with a relatively high presentation level. A more complex listening task, such as speech-in-noise testing, may be a more clinically informative test to evaluate the effects of HIV on speech communication

Predictors and Consequences of Prescription Opioid Use in Women Living With and Without HIV: 20-Year Follow-Up

Objective: To examine predictors and consequences of prescription opioid use among a cohort of women living with HIV (WLWH) and women without HIV from 2000 to 2019. Materials and Methods: The Women's Interagency HIV Study is a multisite, prospective cohort study. Cumulative proportion of visits with prescription opioid use was categorized as follows: minimal (0%-9%), intermediate (10%-39%), and chronic (>40%). Logistic regression examined independent predictors, and proportional hazards regression estimated unadjusted and adjusted hazards of all-cause mortality, comparing intermediate and chronic prescription opioid use with minimal use. Results: Annual prevalence of prescription opioid use significantly increased from 12.6% to 19.3% from 2000 to 2019 (p < 0.0001). Prescription opioid use was minimal in 75%, intermediate in 16%, and chronic in 9% of women. WLWH had 56% higher odds of chronic prescription opioid use compared with women without HIV. Even after adjusting for quality-of-life scores including ratings of pain, women with intermediate and chronic prescription opioid use had greater odds of being sexual minorities (lesbian or bisexual), unemployed, and were more likely to report benzodiazepine and nonprescription substance use compared with those with minimal use. Intermediate and chronic prescription opioid use were each associated with an almost 1.5-fold increased risk of all-cause mortality. Conclusions: Despite federally mandated opioid prescribing guidelines, prescription opioid use and related mortality significantly increased in women experiencing physical and psychosocial vulnerabilities. The higher mortality rate found among prescription opioid users may reflect the many underlying chronic medical and psychosocial conditions for which these opioids were prescribed, as well as complications of opioids themselves. Findings underscore the need for non-opioid and nonpharmacological interventions for chronic pain, particularly in sexual minorities and WLWH. Avoiding concurrent use of opioids with benzodiazepines and nonprescription drugs might reduce mortality

Viremia trajectories of HIV in HIV-positive women in the United States, 1994-2017

IMPORTANCE Viral suppression of HIV is an important treatment goal to decrease morbidity, mortality, and risk of transmission to others. OBJECTIVE To characterize longitudinal HIV viral load outcomes among women enrolled in the Women's Interagency HIV Study (WIHS). DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study of HIV-positive women with semiannual study visits and a minimum of 5 follow-up visits was conducted from 1994 to 2017. The WIHS sites included in this analysis are in Brooklyn and Bronx, New York; Chicago, Illinois; San Francisco, California; andWashington, DC. MAIN OUTCOMES AND MEASURES Women were categorized into groups based on their probability of achieving viral load suppression below 200 copies/mL using logistic trajectory modeling. Multinomial regression analysis was used to identify factors associated with placement in the group with the highest probability of viremia. RESULTS At baseline, the mean (SD) age of the 1989 women was 36.9 (8.0) years, mean CD4+ T-lymphocyte count was 467/mm3, median (interquartile range) HIV RNA was 6200.0 (384.5-41 678.0) copies/mL, and 1305 women (65.6%) were African American. Three trajectory groups were identified with low (568 [28.6%]), intermediate (784 [39.4%]), and high (637 [32.0%]) probability of viremia above 200 copies/mL. The mean (SD) cumulative years of viral suppression were 18.7 (4.0) years, 12.2 (3.1) years, and 5.8 (2.9) years in the respective groups. Factors associated with high probability of viremia included younger age (odds ratio [OR]. 0.99; 95%CI, 0.98-0.99; P = .03), African American race (odds ratio [OR], 2.43; 95%CI, 1.75-3.37), P < .001), Hispanic race/ ethnicity (OR, 1.50; 95%CI, 1.03-2.19; P = .04), increased levels of depressive symptoms (OR, 1.17; 95%CI, 1.01-1.36; P = .03), drug use (OR, 1.23; 95%CI, 1.01-1.51; P = .04), lower CD4+ T-lymphocyte counts (OR, 95%CI, 0.82; 0.80-0.85; P < .001), and unstable housing (OR, 1.25, 95%CI, 1.03-1.50; P = .02). Between 2015 and 2017, 71.2%of women demonstrated sustained viral suppression: 89.6% (310 of 346) of those with lowviremia, 83.4%(346 of 415) with intermediate, and 35.2%(112 of 318) with high probability of viremia. CONCLUSIONS AND RELEVANCE This longitudinal approach suggested that the probability of viremia decreased substantially over time for most participants, including among women with earlier histories of incomplete viral suppression. The findings from this study suggest that continued efforts are needed to address mental health, social, behavioral and structural factors that were identified as associated with high probability of HIV viremia over time

Peripheral artery disease and physical function in women with and without HIV

Objectives: Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women’s Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors. Methods: Analysis included 1839 participants (72% with HIV) with measured ankle – brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status. Results: Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose – response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4 – 9%], 10% for borderline PAD (95% CI: 6 – 13%), 14% for mild PAD (95% CI: 9 – 18%), and 16% for moderate – severe PAD (95% CI: 5 – 25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4 – 14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4þ cell count nor HIV-RNA level was associated with gait speed. Conclusion: In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences

Human Immunodeficiency Virus Is Associated with Elevated FibroScan-Aspartate Aminotransferase (FAST) Score

Background: Whether human immunodeficiency virus (HIV) infection is associated with the development of nonalcoholic steatohepatitis (NASH) remains unclear. The FibroScan-aspartate aminotransferase (FAST) score was developed to identify patients who have histologic NASH with high nonalcoholic fatty liver disease activity score (NAS ≥4) and significant liver fibrosis (≥F2), which has been associated with higher risk of end-stage liver disease. We examined whether HIV infection is associated with elevated FAST score in a large United States (US) cohort. Methods: Vibration-controlled transient elastography was performed in 1309 women without history of chronic viral hepatitis enrolled from 10 US sites: 928 women with HIV (WWH) and 381 women without HIV (WWOH). We used multivariable logistic regression to evaluate associations of HIV, demographic, lifestyle, and metabolic factors with an elevated (>0.35) FAST score. Results: Median age of WWH and WWOH was 51 years and 48 years, respectively. Most (90%) WWH were on antiretroviral therapy and 72% had undetectable HIV RNA. Prevalence of elevated FAST score was higher among WWH compared to WWOH (6.3% vs 1.8%, respectively; P =. 001). On multivariable analysis, HIV infection was associated with 3.7-fold higher odds of elevated FAST score (P =. 002), and greater waist circumference (per 10 cm) was associated with 1.7-fold higher odds (P <. 001). In analysis limited to WWH, undetectable HIV RNA and current protease inhibitor use were independently associated with lower odds of elevated FAST score. Conclusions: Our findings suggest that HIV is an independent risk factor for NASH with significant activity and fibrosis. Studies validating FAST score in persons with HIV are warranted