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Telomere length (TL) is an important indicator of cellular aging. Shorter TL is associated with several age-related diseases including coronary heart disease, heart failure, diabetes, osteoporosis, and cancer. Recently, a DNA methylation-based TL (DNAmTL) estimator has been developed as an alternative method for directly measuring TL. In this study, we examined the association of DNAmTL with cancer prevalence and mortality risk among people with and without HIV in the Veterans Aging Cohort Study Biomarker Cohort (VACS, N = 1917) and Women's Interagency HIV Study Cohort (WIHS, N = 481). We profiled DNAm in whole blood (VACS) or in peripheral blood mononuclear cells (WIHS) using an array-based method. Cancer prevalence was estimated from electronic medical records and cancer registry data. The VACS Index was used as a measure of physiologic frailty. Models were adjusted for self-reported race and ethnicity, batch, smoking status, alcohol consumption, and five cell types (CD4, CD8, NK, B cell, and monocyte). We found that people with HIV had shorter average DNAmTL than those without HIV infection [beta = -0.25, 95% confidence interval (-0.32, -0.18), p = 1.48E-12]. Greater value of VACS Index [beta = -0.002 (-0.003, -0.001), p = 2.82E-05] and higher cancer prevalence [beta = -0.07 (-0.10, -0.03), p = 1.37E-04 without adjusting age] were associated with shortened DNAmTL. In addition, one kilobase decrease in DNAmTL was associated with a 40% increase in mortality risk [hazard ratio: 0.60 (0.44, 0.82), p = 1.42E-03]. In summary, HIV infection, physiologic frailty, and cancer are associated with shortening DNAmTL, contributing to an increased risk of all-cause mortality., (© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Objective: Sexual and physical abuse predict cardiovascular disease (CVD) among women in the general population. Women living with HIV (WLWH) report more abuse and have higher CVD risk compared with other women, yet associations between abuse history and CVD have not been considered among WLWH. This study fills this gap, and describes possible pathways linking abuse to CVD risk among WLWH and women living without HIV (WLWOH)., Methods: Using 25 years of data from the Women's Interagency HIV Study (WIHS; n  = 2734; WLWH n  = 1963; WLWOH n  = 771), we used longitudinal generalized estimating equations (GEE) to test associations between sexual and physical abuse with CVD risk. Framingham (FRS-H) and the American College of Cardiology/American Heart Association-Pooled Cohort Equation (ACC/AHA-PCE) scores were examined. Analyses were stratified by HIV-serostatus., Results: Among WLWH, childhood sexual abuse was associated with higher CVD risk ( βFRS-H  = 1.25, SE = 1.08, P  = 0.005; βACC/AHA-PCE  = 1.14, SE = 1.07, P  = 0.04) compared with no abuse. Adulthood sexual abuse was associated with higher CVD risk for WLWH ( βFRS-H  = 1.39, SE = 1.08, P  < 0.0001) and WLWOH ( βFRS-H  = 1.58, SE = 1.14, P  = 0.0006). Childhood physical abuse was not associated with CVD risk for either group. Adulthood physical abuse was associated with CVD risk for WLWH ( βFRS-H  = 1.44, SE = 1.07; P  < 0.0001, βACC/AHA-PCE  = 1.18, SE = 1.06, P  = 0.002) and WLWOH ( βFRS-H  = 1.68, SE = 1.12, P  < 0.0001; βACC/AHA-PCE  = 1.24, SE = 1.11, P  = 0.03). Several pathway factors were significant, including depression, smoking, and hepatitis C infection., Conclusion: Life course abuse may increase CVD risk among WLWH and women at high risk of acquiring HIV. Some comorbidities help explain the associations. Assessing abuse experiences in clinical encounters may help contextualize cardiovascular risk among this vulnerable population and inform intervention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Epigenome-wide association studies (EWAS) have identified CpG sites associated with HIV infection in blood cells in bulk, which offer limited knowledge of cell-type specific methylation patterns associated with HIV infection. In this study, we aim to identify differentially methylated CpG sites for HIV infection in immune cell types: CD4+ T-cells, CD8+ T-cells, B cells, Natural Killer (NK) cells, and monocytes., Methods: Applying a computational deconvolution method, we performed a cell-type based EWAS for HIV infection in three independent cohorts (Ntotal = 1,382). DNA methylation in blood or in peripheral blood mononuclear cells (PBMCs) was profiled by an array-based method and then deconvoluted by Tensor Composition Analysis (TCA). The TCA-computed CpG methylation in each cell type was first benchmarked by bisulfite DNA methylation capture sequencing in a subset of the samples. Cell-type EWAS of HIV infection was performed in each cohort separately and a meta-EWAS was conducted followed by gene set enrichment analysis., Results: The meta-analysis unveiled a total of 2,021 cell-type unique significant CpG sites for five inferred cell types. Among these inferred cell-type unique CpG sites, the concordance rate in the three cohorts ranged from 96% to 100% in each cell type. Cell-type level meta-EWAS unveiled distinct patterns of HIV-associated differential CpG methylation, where 74% of CpG sites were unique to individual cell types (false discovery rate, FDR <0.05). CD4+ T-cells had the largest number of unique HIV-associated CpG sites (N = 1,624) compared to any other cell type. Genes harboring significant CpG sites are involved in immunity and HIV pathogenesis (e.g. CD4+ T-cells: NLRC5, CX3CR1, B cells: IFI44L, NK cells: IL12R, monocytes: IRF7), and in oncogenesis (e.g. CD4+ T-cells: BCL family, PRDM16, monocytes: PRDM16, PDCD1LG2). HIV-associated CpG sites were enriched among genes involved in HIV pathogenesis and oncogenesis that were enriched among interferon-α and -γ, TNF-α, inflammatory response, and apoptotic pathways., Conclusion: Our findings uncovered computationally inferred cell-type specific modifications in the host epigenome for people with HIV that contribute to the growing body of evidence regarding HIV pathogenesis., Competing Interests: VCM has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences, and ViiV. The remaining authors declare that they have no competing interests., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Parenting has been implicated in a range of youth health outcomes. Positive parenting during adolescence, a critical period of developmental change, may equip youth with the necessary tools for their transition into adulthood and, for youth living with HIV, their transition from pediatric HIV care into adult HIV care. Yet, because few studies have carefully assessed the psychometric properties of parenting instruments applied cross-culturally, the validity of parenting research derived in these contexts remains unclear. This study tested the factor structure of the Children's Report of Parenting Behavior Inventory (CRPBI) in a novel setting (e.g., Rwanda), context (e.g., youth with HIV), and considering multiple informants (caregivers and youth). Youth ( N = 330) were on average 16.78 years of age; 51% self-identified as female. Caregivers ( N = 330) were on average 44.40 years of age; 80% self-identified as female. The factor structures for youth and caregiver CRPBIs appeared to be indicative of two dimensions: (a) acceptance and positive involvement, and (b) hostile detachment and rejection. The CRPBI worked well for youth reports and showed predictive validity. The CRPBI worked less well for caregivers, necessitating the removal of 10 items, seven of which were related to hostile detachment and rejection. The reliability of both CRPBIs was supported. The CRPBI appears to function well for youth, but not as well for caregivers, in this novel context with this unique population of youth with HIV. The findings support careful assessment of instruments developed in high-resource settings and then used in resource-constrained contexts. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Women living with HIV (WLWH) experience high rates of depression but are underrepresented in mental health research. Positive emotions are associated with beneficial health outcomes in WLWH and should be a targeted component of psychological interventions in this population. Positive psychological interventions aim to increase positive emotions through the use of simple exercises, such as keeping a gratitude journal. We conducted a single-arm feasibility/acceptability study of a five-week, self-guided, web-based positive affect skills intervention in a sample of WLWH ( N  = 23) who also participate in a longitudinal observational study, the Women's Interagency HIV Study. The intervention was feasible as measured by home practice and post-intervention assessment completion, and acceptable as measured by exit interview feedback regarding recommendation of the program to friends or others living with HIV. On average, participants completed home practice for about 8 out of 9 skills. The mean response for recommendation of the program to a friend was 9.26/10 (SD = 1.63) and the mean response for recommendation of the program to others living with HIV was 9.68/10 (SD = 0.82). Participant feedback will be used to adapt and enhance the delivery of this intervention. Further studies are needed to assess efficacy and impact on psychological outcomes.

Mental health and substance use epidemics interact to create psychosocial syndemics, accelerating poor health outcomes. Using latent class and latent transition analyses, we identified psychosocial syndemic phenotypes and their longitudinal transition pathways among sexual minority men (SMM) in the Multicenter AIDS Cohort Study (MACS, n = 3,384, mean age 44, 29% non-Hispanic Black, 51% with HIV). Self-reported depressive symptoms and substance use indices (i.e., smoking, hazardous drinking, marijuana, stimulant, and popper use) at the index visit, 3-year and 6-year follow-up were used to model psychosocial syndemics. Four latent classes were identified: "poly-behavioral" (19.4%), "smoking and depression" (21.7%), "illicit drug use" (13.8%), and "no conditions" (45.1%). Across all classes, over 80% of SMM remained in that same class over the follow-ups. SMM who experienced certain psychosocial clusters (e.g., illicit drug use) were less likely to transition to a less complex class. These people could benefit from targeted public health intervention and greater access to treatment resources., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Food insecurity disproportionately affects people with HIV and women in the United States (US). More evidence is needed to understand the interplay between levels of food insecurity and levels of antiretroviral therapy (ART) adherence over time, as well as how food insecurity relates to engagement in HIV care. We used random effects models with longitudinal data from the US Women's Interagency HIV Study to estimate the (1) adjusted associations of current and 6-month lagged food security with ART adherence categories (n = 1646), and (2) adjusted associations of food security with engagement-in-care (n = 1733). Very low food security was associated with a higher relative risk of ART non-adherence at prior and current visits compared with food security, and this association increased across non-adherence categories. Very low food security was associated with lower odds of receiving HIV care and higher odds of a missed visit. Food insecurity among US women with HIV is associated with poorer engagement in care and degree of ART non-adherence over time., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Heavy drinking, smoking, and depression are common among people with HIV. Little is known about the co-occurring, synergistic effect of having two or more of these conditions long-term -a sustained syndemic - on mortality among women with HIV (WWH)., Methods: Data from 3282 WWH of the Women's Interagency HIV Study from 1994 to 2017 were utilized. National Death Index review identified cause of death (n=616). Sustained syndemic phenotypes were based on membership in high-risk groups defined by group-based trajectory models of repeated self-reported alcohol use, smoking, and depressive symptoms and their co-occurrence. Cox proportional hazard models estimated associations of sustained syndemic phenotypes with all-cause, non-AIDS, and non-overdose mortality, adjusting for age, race/ethnicity, education, enrollment wave, illicit drug use, and time-varying HIV viral load and CD4+ T-cell count., Results: WWH were 58% Black and 26% Hispanic, with a mean baseline age of 36.7 years. Syndemic phenotypes included zero (45%, n=1463), heavy drinking only (1%, n=35), smoking only (28%, n=928), depressive symptoms only (9%, n=282), and 2+ trajectories (17%, n=574). Compared to zero trajectories, having 2+ trajectories was associated with 3.93 times greater all-cause mortality risk (95% CI 3.07, 5.04) after controlling for confounders and each high-risk trajectory alone. These findings persisted in sensitivity analyses, removing AIDS- and overdose-related mortalities., Conclusions: Clustering of 2+ conditions of heavy drinking, smoking, and depression affected nearly one in five WWH and was associated with higher mortality than zero or one condition. Our findings underscore the need for coordinated screening and parsimonious treatment strategies for these co-occurring conditions., Competing Interests: Declaration of Competing Interest Dr. Kizer reports stock ownership in Abbott, Bristol Myers Squibb, Johnson & Johnson, Medtronic, Merck, and Pfizer. Dr. Lahiri receives grant funding from Merck and serves on the Advisory Board for Theratechnologies, Inc. Dr. Adimora has received fees for consulting from Merck and Gilead. Merck and Gilead have provided her institution with funding for her research. Dr Palella has been a consultant or on the Speakers’ Bureau for ViiV, Gilead, Janssen and Merck. None of the other authors had any financial or other conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Women with HIV (WHIV) in the United States face many challenges with adherence to antiretroviral therapy (ART), and suboptimal adherence often leads to virologic failure. This study aimed to determine the association between ART adherence trajectories and the risk of virologic failure., Methods: We included WHIV (aged 18 years or older) enrolled in the Women's Interagency HIV Study in the United States from April 2014 to September 2019 who had at least 2 consecutive measurements of HIV RNA and ≥3 measurements of self-reported adherence. Group-based trajectory modeling was used to identify adherence trajectories. Cox proportional hazard ratios were used to measure the association., Main Outcome Measure: Virologic failure was defined as HIV RNA ≥200 copies/mL at 2 consecutive visits., Results: We included 1437 WHIV (median age 49 years). Of all women, 173 (12.0%) experienced virologic failure. Four adherence trajectories were identified, namely "consistently high" (26.3%), "moderate increasing" (9.5%), "moderate decreasing" (30.6%), and "consistently low" (33.5%). Women in the consistently low adherence group consumed alcohol and experienced depression more than other groups. Compared with the "consistently high" trajectory, the risk of virologic failure was higher among women with "consistently low" [adjusted hazard ratio (aHR) 2.8; 95% confidence interval (CI): 1.6 to 4.9; P < 0.001] and "moderate decreasing" adherence trajectories (aHR 1.8; 95% CI: 1.0 to 3.2; P = 0.04), but it was similar to those with "moderate increasing" adherence trajectory (aHR 1.0; 95% CI: 0.4 to 2.5; P = 0.94)., Conclusions: Adherence to ART remains a challenge among WHIV. Multilevel behavioral interventions to address poor adherence, alcohol consumption, and depression are needed., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Persistent inflammation contributes to the development of cardiovascular disease (CVD) as an HIV-associated comorbidity. Innate immune cells such as monocytes are major drivers of inflammation in men and women with HIV. The study objectives are to examine the contribution of circulating non-classical monocytes (NCM, CD14dimCD16+) and intermediate monocytes (IM, CD14+CD16+) to the host response to long-term HIV infection and HIV-associated CVD. Women with and without chronic HIV infection (H) were studied. Subclinical CVD (C) was detected as plaques imaged by B-mode carotid artery ultrasound. The study included H-C-, H+C-, H-C+, and H+C+ participants (23 of each, matched on race/ethnicity, age and smoking status), selected from among enrollees in the Women's Interagency HIV Study. We assessed transcriptomic features associated with HIV or CVD alone or comorbid HIV/CVD comparing to healthy (H-C-) participants in IM and NCM isolated from peripheral blood mononuclear cells. IM gene expression was little affected by HIV alone or CVD alone. In IM, coexisting HIV and CVD produced a measurable gene transcription signature, which was abolished by lipid-lowering treatment. In NCM, versus non-HIV controls, women with HIV had altered gene expression, irrespective of whether or not they had comorbid CVD. The largest set of differentially expressed genes was found in NCM among women with both HIV and CVD. Genes upregulated in association with HIV included several potential targets of drug therapies, including LAG3 (CD223). In conclusion, circulating monocytes from patients with well controlled HIV infection demonstrate an extensive gene expression signature which may be consistent with the ability of these cells to serve as potential viral reservoirs. Gene transcriptional changes in HIV patients were further magnified in the presence of subclinical CVD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy., Methods: We included women with HIV (aged ≥ 18) enrolled in the Women's Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy., Results: Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group., Conclusions: The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence., (© 2023. The Author(s).)

Objective: Hypertension is a critical cause of cardiovascular disease, and women with HIV have a higher prevalence of hypertension than women without HIV. The relationship between hypertension and mortality has not been well characterized in women with treated HIV. Here, we estimate the effect of hypertension on 1-year risk of all-cause mortality among women with HIV on antiretroviral therapy (ART) in the United States., Design: An analysis of multicenter, observational cohort data from the Women's Interagency HIV Study (WIHS) collected between 1995 and 2019., Methods: We included women with HIV who reported ever using ART. We used parametric g-computation to estimate the effect of hypertension (SBP ≥140  mmHg, DBP ≥90 mmHg, or use of hypertensive medication) on all-cause mortality within 1 year of a WIHS visit., Results: Among 2929 unique women, we included 57 034 visits with a median age of 45 (interquartile range: 39, 52) years. Women had hypertension at 34.5% of visits, and 641 deaths occurred within 1 year of a study visit. Comparing women at visits with hypertension to women at visits without hypertension, the standardized 1-year risk ratio for mortality was 1.16 [95% confidence interval (95% CI): 1.01-1.33]. The risk ratios were higher in Hispanic (risk ratio: 1.23, 95% CI: 0.86-1.77) and non-Hispanic black women (risk ratio: 1.19, 95% CI: 1.04-1.37) and lower in non-Hispanic white women (risk ratio: 0.93, 95% CI: 0.58-1.48)., Conclusion: Among women with treated HIV, those with hypertension, compared with those without, had an increased 1-year risk of all-cause mortality., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS)., Methods: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations between participant characteristics and SU treatment., Results: Among 2559 women (1802 women living with HIV [WWH], 757 women without HIV), 14% reported current SU. Among those with current SU (n = 367), 71% reported crack/cocaine followed by 40% reporting opioids, and 42% reported any treatment in the past year. The most common treatments were methadone (64%), Narcotics Anonymous (29%), inpatient programs (28%), and outpatient programs (16%). Among women using opioids (n = 147), 67% reported methadone use in the past year compared to 5% using buprenorphine/naloxone. Multivariable analysis showed lower odds of treatment utilization among WWH with concurrent alcohol or marijuana use. Visiting a psychiatrist/counselor was associated with higher odds of treatment. Among WWH, SU treatment was not associated with HIV-related clinical outcomes., Conclusions: Treatment utilization was high, especially for methadone use. Our results highlight opportunities for accessing SU treatment for WWH, such as the need to prioritize buprenorphine and comprehensive, wraparound services in HIV care settings., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Resilience and optimism may not only have main effects on health outcomes, but may also moderate and buffer negative effects of stressors. We examined whether dispositional resilience and optimism moderate the associations between HIV-related stigma in health care settings and health-related outcomes (trust in HIV health care providers and depression symptoms) among women living with HIV (WLHIV). One thousand four hundred five WLHIV in nine US cities completed validated questionnaires for cross-sectional analyses. Higher self-reported experienced and anticipated stigma and lower resilience and optimism were associated with higher depression symptoms and with lower trust in HIV providers. Importantly, resilience moderated the effects of experienced stigma (but not of anticipated stigma): When resilience was high, the association of experienced stigma with higher depression symptoms and lower trust in HIV providers was weaker compared with when resilience was low. Further, significant moderation effects suggested that when optimism was high, experienced and anticipated stigma was both less strongly associated with depression symptoms and with lower trust in one's HIV care providers compared with when optimism was low. Thus, the effects of experienced stigma on depression symptoms and provider trust were moderated by both resilience and optimism, but the effects of anticipated stigma were moderated only by optimism. Our findings suggest that in addition to their main effects, resilience and optimism may function as buffers against the harmful effects of stigma in health care settings. Therefore, optimism and resilience may be valuable intervention targets to reduce depression symptoms or improve trust in providers among populations that experience or anticipate stigma, such as WLHIV.

Rationale: Human immunodeficiency virus (HIV) infection is associated with chronic lung disease and impaired pulmonary function; however, longitudinal pulmonary function phenotypes in HIV are undefined. Objectives: To identify pulmonary function trajectories, their determinants, and outcomes. Methods: We used data from participants with HIV in the Pittsburgh HIV Lung Cohort with three or more pulmonary function tests between 2007 and 2020. We analyzed post-bronchodilator forced expiratory volume in 1 second (FEV 1 ), forced vital capacity (FVC), and FEV 1 /FVC, and diffusing capacity of the lung for carbon monoxide (Dl CO ) using group-based trajectory modeling to identify subgroups of individuals whose measurements followed a similar pattern over time. We examined the association between participant characteristics and trajectories using multivariable logistic regression. In exploratory adjusted analyses restricted to individuals with available plasma cytokine data, we investigated the association between 18 individual standardized cytokine concentrations and trajectories. We compared mortality, dyspnea prevalence, respiratory health status, and 6-minute-walk distance between phenotypes. Results: A total of 265 participants contributed 1,606 pulmonary function measurements over a median follow-up of 8.1 years. We identified two trajectories each for FEV 1 and FVC: "low baseline, slow decline" and "high baseline, rapid decline." There were three trajectory groups for FEV 1 /FVC: "rapid decline," "moderate decline," and "slow decline." Finally, we identified two trajectories for Dl CO : "baseline low" and "baseline high." The low baseline, slow decline FEV 1 and FVC, rapid decline, and moderate decline FEV 1 /FVC, and baseline low Dl CO phenotypes were associated with increased dyspnea prevalence, worse respiratory health status, and decreased 6-minute-walk distance. The baseline low Dl CO phenotype was also associated with worse mortality. Current smoking and pack-years of smoking were associated with the adverse FEV 1 , FEV 1 /FVC, and Dl CO phenotypes. Detectable viremia was the only HIV marker associated with the adverse Dl CO phenotype. C-reactive protein and endothelin-1 were associated with the adverse FEV 1 and FVC phenotypes, and endothelin-1 trended toward an association with the adverse Dl CO phenotype. Conclusions: We identified novel, distinct longitudinal pulmonary function phenotypes with significant differences in characteristics and outcomes. These findings highlight the importance of lung dysfunction over time in people with HIV and should be validated in additional cohorts.

Objective: To test whether substance use mediates the associations between gender-based violence (GBV) and suboptimal adherence to antiretroviral therapy (ART), and GBV and poor engagement in care, among women living with HIV (WLHIV) in the United States (US)., Design: We analyzed longitudinal data collected among 1717 WLHIV in the Women's Interagency HIV Study (WIHS)., Methods: From 2013 to 2017, WLHIV completed semi-annual assessments on GBV, substance use, and HIV treatment and care. Adjusted multilevel logistic regression models were built to estimate the impact of GBV on; suboptimal (<95%) adherence and at least one missed HIV care appointment without rescheduling in the past 6 months. Mediation analyses were performed to test whether heavy drinking and illicit drug use mediated the associations between GBV and the two HIV outcomes., Results: The mean age was 47 (standard deviation = 9), 5% reported experiencing GBV, 17% reported suboptimal adherence and 15% reported at least one missed appointment in the past 6 months. Women who experienced GBV had a significantly higher odds of suboptimal adherence [adjusted odds ratio (aOR) = 1.99; 95% confidence interval (CI) = 1.40-2.83] and missed appointments (aOR = 1.92, 95% CI = 1.32-2.33). Heavy drinking and illicit drug use mediated 36 and 73% of the association between GBV and suboptimal adherence and 29 and 65% of the association between GBV and missed appointments, respectively., Conclusions: Substance use is an underlying mechanism through which GBV affects outcomes along the HIV care continuum among WLHIV in the US. To optimize HIV treatment and care among women, interventions should address the combined epidemics of substance use, violence, and HIV., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Fracture rates have been reported to be higher among older women living with HIV (WLWH) than HIV- women. Hormone therapy with estrogen can reduce vasomotor symptoms (VMS) associated with menopause and prevent fractures. As data are limited on the benefits of hormone therapy use in WLWH, we examined associations of hormone therapy, use and fractures., Methods: A prospective study of 1765 (1350 WLWH and 415 HIV-) postmenopausal Women's Interagency HIV Study (WIHS) participants was performed, including self-reported hormone therapy, use and fracture data from 2003 to 2017. Proportional hazard models determined predictors of new fractures at any site or at typical fragility fracture sites (hip, spine, wrist)., Results: At the first postmenopausal visit, the median (IQR) age of WLWH was slightly younger than HIV- women [49.8 (46.4-53) vs. 50.7 (47.5-54), P  = 0.0002] and a smaller proportion of WLWH reported presence of VMS (17% vs. 26%, P  < 0.0001). A greater proportion of WLWH than HIV- women reported hormone therapy use (8% vs. 4%, P  = 0.007) at the first postmenopausal visit. In multivariate analyses, white race and smoking were significant predictors of incident fracture at any site but hormone therapy ( P  = 0.69) and HIV status ( P  = 0.53) were not., Conclusion: Our study did not find evidence of benefit or harm with regards to fracture outcomes in postmenopausal WLWH receiving hormone therapy. Further research is needed to determine whether hormone therapy has benefits beyond treatment of VMS, such as prevention of adverse aging-associated outcomes., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women's adherence and long-term HIV outcomes., Objective: This study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment., Methods: The study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance., Results: This study was funded in March 2021. Columbia University's IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023., Conclusions: This study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting., International Registered Report Identifier (irrid): DERR1-10.2196/35646., (©Morgan M Philbin, Tara McCrimmon, Victoria A Shaffer, Deanna Kerrigan, Margaret Pereyra, Mardge H Cohen, Oluwakemi Sosanya, Anandi N Sheth, Adaora A Adimora, Elizabeth F Topper, Aadia Rana, Bani Tamraz, Lakshmi Goparaju, Tracey E Wilson, Maria Alcaide. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 13.09.2022.)

The prevalence of HIV-associated neurocognitive impairment persists despite highly effective antiretroviral therapy (ART). In this study we explore the role of internalized stigma, acceptance of negative societal characterizations, and perceptions about people living with HIV (PLWH) on neurocognitive functioning (executive function, learning, memory, attention/working memory, psychomotor speed, fluency, motor skills) in a national cohort of women living with HIV (WLWH) in the United States. We utilized observational data from a multicenter study of WLWH who are mostly African American living in low-resource settings. Neurocognitive function was measured using an eight-test battery. A multiple linear regression model was constructed to investigate the relationship between internalized stigma and overall neurocognitive functioning (mean of all neurocognitive domain standardized T -scores), adjusting for age, education, race, previous neuropsychological battery scores, illicit drug use, viral load, and years on ART. Our analysis revealed that internalized HIV-related stigma is significantly associated with worse performance on individual domain tests and overall neurocognitive performance ( B  = 0.27 , t  = 2.50, p  = 0.01). This suggests HIV-related internalized stigma may be negatively associated with neurocognitive functioning for WLWH. This finding highlights a specific psychosocial factor associated with poor neurocognitive function that may be targeted to better promote the health of PLWH. Future research on the longitudinal relationship between these variables and the effects of other stigma dimensions on poor neurocognitive function would provide further insights into the pathways explaining the relationship between internalized stigma and neurocognition.

Background: As employment, financial status, and residential location change, people can gain, lose, or switch health insurance coverage, which may affect care access and health. Among Women's Interagency HIV Study participants with HIV and participants at risk for HIV attending semiannual visits at 10 U.S. sites, we examined whether the prevalence of coverage types and rates of coverage changes differed by HIV status and Medicaid expansion in their states of residence., Methods: Geocoded addresses were merged with dates of Medicaid expansion to indicate, at each visit, whether women lived in Medicaid expansion states. Age-adjusted rate ratios (RRs) and rate differences of self-reported insurance changes were estimated by Poisson regression., Results: From 2008 to 2018, 3,341 women (67% Black, 71% with HIV) contributed 43,329 visits at aged less than 65 years (27% under Medicaid expansion). Women with and women without HIV differed in their proportions of visits at which no coverage (14% vs. 19%; p < .001) and Medicaid enrollment (61% vs. 51%; p < .001) were reported. Women in Medicaid expansion states reported no coverage and Medicaid enrollment at 4% and 69% of visits, respectively, compared with 20% and 53% of visits for those in nonexpansion states. Women with HIV had a lower rate of losing coverage than those without HIV (RR, 0.81; 95% confidence interval [CI], 0.70 to 0.95). Compared with nonexpansion, Medicaid expansion was associated with lower coverage loss (RR, 0.62; 95% CI, 0.53 to 0.72) and greater coverage gain (RR, 2.32; 95% CI, 2.02 to 2.67), with no differences by HIV status., Conclusions: Both women with HIV and women at high risk for HIV in Medicaid expansion states had lower coverage loss and greater coverage gain; therefore, Medicaid expansion throughout the United States should be expected to stabilize insurance for women and improve downstream health outcomes., (Copyright © 2022 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

Neuropsychiatric complications are common among women with HIV (WWH). The pathophysiological mechanisms underlying these complications are not fully known but likely driven in part by immune modulation. We examined associations between T-cell activation states which are required to mount an effective immune response (activation, co-stimulation/normal function, exhaustion, senescence) and neuropsychiatric complications in WWH. 369 WWH (78% HIV RNA undetectable/<20cp/mL) enrolled in the Women's Interagency HIV Study completed neuropsychological testing and measures of depression (Center for Epidemiological Studies Depression Scale-CES-D), self-reported stress levels (Perceived Stress Scale-10), and post-traumatic stress (PTSD Checklist-Civilian Scale). Multiparametric flow cytometry evaluated T-cell activation state. Partial least squares regressions were used to examine T-cell phenotypes and neuropsychiatric outcome associations after confounder adjustment. In the total sample and among virally suppressed (VS)-WWH, CD4 + T-cell exhaustion was associated with poorer learning and attention/working memory ( P 's < 0.05). In the total sample, CD4 + T-cell activation was associated with better attention/working memory and CD8 + T-cell co-stimulation and senescence was associated with poorer executive function ( P 's < 0.05). For mental health outcomes, in the total sample, CD4 + T-cell activation was associated with more perceived stress and CD4 + T-cell exhaustion was associated with less depressive symptoms ( P 's < 0.05). Among VS-WWH, CD4 + senescence was associated with less perceive stress and CD8 + T-cell co-stimulation and senescence was associated with higher depression ( P's  < 0.05). Together, results suggest the contribution of peripheral CD4 + and CD8 + T-cell activation status to neuropsychiatric complications in WWH., Competing Interests: LHR is a consultant for Digital Artefacts, Inc. All coauthors have nothing to disclose., (© 2022 The Authors. Published by Elsevier Inc.)

Objectives: This study of people with HIV (PWH) and those without HIV conducted during the COVID-19 pandemic in the United States in 2020 examines the impact of posttraumatic stress disorder (PTSD) on COVID-19 burden, defined as pandemic-related disruptions., Methods: Data consisted of survey responses on PTSD among participants (N = 2434) enrolled in the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV (WIHS) cohorts. Unadjusted and adjusted regression models were used to examine the association of PTSD with COVID-19 burden (overall and domain-specific burdens). Quasi-Poisson regression models were used to assess associations with the COVID-19 burden score and 2 domain-specific burdens: (1) changes in resources and (2) interruptions in health care. Analyses was adjusted for age, race/ethnicity, HIV serostatus, current smoking status, number of comorbidities, education, and study regions., Results: Study participants were a median age of 58 (interquartile range, 52-65) years. In both bivariate and multivariable models, PTSD severity was associated with greater overall COVID-19 burden. PTSD severity was associated with the number of resource changes and number of interruptions in medical care. These findings were also consistent across cohorts (MACS/WIHS) and across HIV serostatus, suggesting a greater risk for COVID-19 burden with greater PTSD severity, which remained significant after controlling for covariates., Conclusions: This study builds on emerging literature demonstrating the impact of mental health on the burden and disruption associated with the COVID-19 pandemic, providing context specific to PWH. The ongoing pandemic requires structural and social interventions to decrease disruption to resources and health resource needs among these vulnerable populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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. Clinical Trial Registration Number: NCT00000797.

Background: This mixed methods study identified positive psychological factors and life themes expressed in autobiographical narratives of predominantly Black women living with HIV (WLWH) and investigated these in relation to depressive symptoms, antiretroviral therapy (ART) adherence (≥ 95% of time), and undetectable HIV viral load (VL) (< 80 copies/ml)., Method: Ninety-eight WLWH from the Women's Interagency HIV Study Chicago site (M age = 45.3; 91% Black) narrated three autobiographical life turning points, reliably coded for positive factors and life themes. ART adherence, VL and depressive symptoms, assessed with Center for Epidemiologic Studies Depression Scale total score (TOT) including its four factors (negative affect (NA), positive affect (PA), somatic symptoms (SS), and interpersonal problems (IP)), were collected over two time points: concurrently with narratives and 6 months later. Composite scores across the two time points were used in all analyses., Results: Ten positive psychological factors (gratitude, insight, compassion, meaning-making, acceptance, mindfulness, generativity, optimism, self-reliance, and benevolent God beliefs) and three positive life themes (health improvements, positive relationships, and accomplishments) were identified in narratives. Higher accomplishments, overall positive factors, insight, mindfulness, self-reliance, optimism, meaning-making, and acceptance related to lower depressive symptoms (TOT, NA, SS, or IP). Positive factors and life themes did not significantly relate to PA. Higher compassion related to higher ART adherence. Higher accomplishments related to undetectable VL independent of ART adherence., Conclusion: Findings that positive psychological factors and life accomplishments may relate to better health, especially to lower depression, potentially contribute to developing positive psychology interventions for Black WLWH., (© 2021. International Society of Behavioral Medicine.)

Introduction: Lifestyle improvements are key modifiable risk factors for Type 2 diabetes mellitus (DM) however specific influences of biologically active dietary metabolites remain unclear. Our objective was to compare non-targeted plasma metabolomic profiles of women with versus without confirmed incident DM. We focused on three lipid classes (fatty acyls, prenol lipids, polyketides)., Materials and Methods: Fifty DM cases and 100 individually matched control participants (80% with human immunodeficiency virus [HIV]) were enrolled in a case-control study nested within the Women's Interagency HIV Study. Stored blood samples (1-2 years prior to DM diagnosis among cases; at the corresponding timepoint among matched controls) were assayed in triplicate for metabolomics. Time-of-flight liquid chromatography mass spectrometry with dual electrospray ionization modes was utilized. We considered 743 metabolomic features in a two-stage feature selection approach with conditional logistic regression models that accounted for matching strata., Results: Seven features differed by DM case status (all false discovery rate-adjusted q<0.05). Three flavonoids (two flavanones, one isoflavone) were respectively associated with lower odds of DM (all q<0.05), and sorbic acid was associated with greater odds of DM (all q<0.05)., Conclusion: Flavonoids were associated with lower odds of incident DM while sorbic acid was associated with greater odds of incident DM., Competing Interests: The authors have declared that no competing interests exist.

Background: Adolescents living with HIV have elevated mental distress and suboptimal antiretroviral therapy (ART) adherence., Setting: Two urban clinics in Kigali, Rwanda., Methods: A 2-arm individual randomized controlled trial compared Trauma-Informed Cognitive Behavioral Therapy enhanced to address HIV (TI-CBTe) with usual care (time-matched, long-standing, unstructured support groups) with 356 12- to 21-year-old (M = 16.78) Rwandans living with HIV. TI-CBTe included 6 group-based 2-hour sessions led by trained and supervised 21- to 25-year-old Rwandans living with HIV. Participants reported their ART adherence, depression/anxiety, and Post-Traumatic Stress Disorder symptoms at baseline, 6, 12, and 18 months., Results: ART adherence was relatively high at baseline, and youth reported elevated rates of depression/anxiety and trauma symptoms. There were no differential treatment effects on adherence, but depression/anxiety improved over time. Youth with lower depression/anxiety at baseline seemed to benefit more from TI-CBTe than usual care, whereas women with high baseline distress seemed to benefit more from usual care. Youth were less likely to score in high Post-Traumatic Stress Disorder symptom categories at the follow-up, with no differential treatment effects., Conclusions: TI-CBTe did not outperform usual care on ART adherence, possibly reflecting relatively high adherence at baseline, simplified medication regimens over time, a strong comparison condition, or because youth assigned to TI-CBTe returned to their support groups after the intervention. TI-CBTe was more effective for youth with lower depression/anxiety symptoms, whereas youth with high distress benefitted more from the support groups. TI-CBTe was feasible and acceptable, and young adults living with HIV were able to deliver a mental health intervention with fidelity. The powerful nature of the comparison group, ongoing support groups, points to the potential value of locally crafted interventions in low-resource settings., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Assessing the effect of alcohol consumption on biological age is essential for understanding alcohol use-related comorbidities and mortality. Previously developed epigenetic clocks are mainly based on DNA methylation in heterogeneous cell types, which provide limited knowledge on the impacts of alcohol consumption at the individual cellular level. Evidence shows that monocytes play an important role in both alcohol-induced pathophysiology and the aging process. In this study, we developed a novel monocyte-based DNA methylation clock (MonoDNAmAge) to assess the impact of alcohol consumption on monocyte age., Methods: A machine learning method was applied to select a set of chronological age-associated DNA methylation CpG sites from 1202 monocyte methylomes. Pearson correlation was tested between MonoDNAmAge and chronological age in three independent cohorts (N total  = 2242). Using the MonoDNAmAge clock and four established clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge), we then evaluated the effect of alcohol consumption on epigenetic aging in the three cohorts [i.e., Yale Stress Center Community Study (YSCCS), Veteran Aging Cohort Study (VACS), Women's Interagency HIV Study (WIHS)] using linear and quadratic models., Results: The MonoDNAmAge, comprised of 186 CpG sites, was moderately to strongly correlated with chronological age in the three cohorts (r = 0.90, p = 3.12E-181 in YSCCS; r = 0.54, p = 1.75E-96 in VACS; r = 0.66, p = 1.50E-60 in WIHS). More importantly, we found a nonlinear association between MonoDNAmAge and alcohol consumption (p model  = 4.55E-08, p x 2  = 7.80E-08 in YSCCS; p model  = 1.85E-02, p x 2  = 3.46E-02 in VACS). Heavy alcohol consumption increased EAA MonoDNAmAge up to 1.60 years while light alcohol consumption decreased EAA MonoDNAmAge up to 2.66 years. These results were corroborated by the four established epigenetic clocks (i.e., HorvathDNAmAge, HannumDNAmAge, PhenoDNAmAge, GrimDNAmAge)., Conclusions: The results suggest a nonlinear relationship between alcohol consumption and its effects on epigenetic age. Considering adverse effects of alcohol consumption on health, nonlinear effects of alcohol use should be interpreted with caution. The findings, for the first time, highlight the complex effects of alcohol consumption on biological aging., (© 2022 by the Research Society on Alcoholism.)

In this mixed-methods study, we examine the relationship between provider communication and patient health literacy on HIV continuum of care outcomes among women living with HIV in the United States. We thematically coded qualitative data from focus groups and interviews (N = 92) and conducted mediation analyses with quantitative survey data (N = 1455) collected from Women's Interagency HIV Study participants. Four qualitative themes related to provider communication emerged: importance of respect and non-verbal cues; providers' expressions of condescension and judgement; patient health literacy; and unclear, insufficient provider communication resulting in diminished trust. Quantitative mediation analyses suggest that higher health literacy is associated with higher perceived patient-provider interaction quality, which in turn is associated with higher levels of trust in HIV providers, improved antiretroviral medication adherence, and reduced missed clinical visits. Findings indicate that enhancing provider communication and bolstering patient health literacy could have a positive impact on the HIV continuum of care., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long-acting injectable (LAI) modalities have been developed for ART and PrEP. Women face unique barriers to LAI use yet little research has examined women's perceptions of potential LAI HIV therapy candidates. We conducted 89 in-depth interviews at six Women's Interagency HIV Study (WIHS) sites with women living with HIV (n = 59) and HIV-negative women (n = 30) from 2017 to 2018. Interviews were recorded, transcribed, and analyzed using thematic content analysis. Participants identified specific sub-populations who could most benefit from LAI over daily pills: (1) young people; (2) women with childcare responsibilities; (3) people with adherence-related psychological distress; (4) individuals with multiple sex partners; and (5) people facing structural insecurities such as homelessness. Women are underserved by current HIV care options and their perspectives are imperative to ensure a successful scale-up of LAI PrEP and LAI ART that prioritizes equitable access and benefit for all individuals., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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 CD4+ 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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: At the start of the COVID-19 pandemic, HIV experts suggested that an increase in mental health diagnoses and substance use among people living with HIV (PLHIV) may be an unintended consequence of COVID-19 mitigation efforts (e.g., limiting social contact). We evaluated short-term trajectories in binge drinking, marijuana, and recreational drug use in a prospective cohort of PLHIV., Methods: Data (N = 2121 PLHIV) consist of survey responses on substance use behaviors from two pre-COVID-19 (October 2018-September 2019) and one COVID-19-era (April 2020-September 2020) timepoints within the MACS/WIHS Combined Cohort Study (MWCCS). We conducted group-based trajectory models, triangulated with generalized linear mixed models, to assess changes in binge drinking, daily marijuana use, and recreational drug use at the start of the pandemic. Controlling for age and race/ethnicity, we tested whether trajectories differed by sex and early-pandemic depressive symptoms, loneliness, and social support., Results: Group-based trajectory models yielded two trajectory groups for binge drinking (none vs. any), marijuana (none/infrequent vs. daily), and recreational drug use (none vs. any). Binge drinking and recreational drug use decreased at the beginning of the pandemic. Generalized linear mixed model supported these trends. Consistent with prior research, male sex and having depressive symptoms early pandemic were positively associated with each substance use outcomes. Social support was inversely associated with recreational drug use., Conclusions: Contrary to hypotheses, problematic substance use behaviors decreased from pre-pandemic to the post-pandemic follow-up in our sample of PLHIV. Ongoing surveillance is needed to assess whether this pattern persists as the pandemic continues., (Copyright © 2022. Published by Elsevier B.V.)

Background: Gender-based violence (GBV) is associated with poorer engagement in HIV care and treatment. However, there is a dearth of research on the psychological (eg, mental health) and structural (eg, food insecurity) factors that mediate and moderate this association. GBV could lead to poor mental health, which in turn affects adherence, whereas food insecurity could worsen the effect of GBV on engagement in care. This study uses data from the Women's Interagency HIV Study to address these gaps., Methods: Women completed 6 assessments from 2013 to 2016 on GBV, mental health, food insecurity, adherence to antiretroviral therapy, and missed HIV care appointments in the past 6 months. Multilevel logistic regression models estimated associations between GBV and engagement in care and whether associations were mediated by depression, generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) and moderated by food insecurity., Results: GBV was associated with higher odds of suboptimal adherence (adjusted odds ratio: 1.88; 95% confidence interval: 1.24 to 2.87) and missed appointments (adjusted odds ratio: 1.76; 95% confidence interval: 1.16 to 2.67). The association between GBV and adherence was mediated by depressive symptoms, GAD, and PTSD, accounting for 29.7%, 15.0%, and 16.5%, respectively, of the total association. The association between GBV and missed appointments was mediated by depression and GAD, but not PTSD, with corresponding figures of 25.2% and 19.7%. Associations did not differ by food insecurity., Conclusions: GBV is associated with suboptimal engagement in care, which may be explained by mental health. Interventions should address women's mental health needs, regardless of food insecurity, when improving engagement in HIV care., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Social support is associated with improved HIV care and quality of life. We utilized latent class analysis to identify three classes of baseline emotional and tangible perceived social support, termed "Strong", "Wavering" and "Weak". "Weak" vs. "Strong" perceived social support was associated over time with an 8% decreased risk of optimal antiretroviral therapy (ART) adherence for emotional and 6% decreased risk for tangible perceived social support. Importantly, "Wavering" vs "Strong" social support also showed a decreased risk of ART adherence of 6% for emotional and 3% for tangible support. "Strong" vs. "Weak" perceived support had a similar association with undetectable viral load, but the association for "Strong" vs. "Wavering" support was not statistically significant. Intensity of social support is associated with HIV care outcomes, and strong social support may be needed for some individuals. It is important to quantify the level or intensity of social support that is needed to optimize HIV outcomes., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: The aim of this study was to define a smoking cessation 'cascade' among USA women with and without HIV and examine differences by sociodemographic characteristics., Design: An observational cohort study using data from smokers participating in the Women's Interagency HIV Study between 2014 and 2019., Methods: We followed 1165 women smokers with and without HIV from their first study visit in 2014 or 2015 until an attempt to quit smoking within approximately 3 years of follow-up, initial cessation (i.e. no restarting smoking within approximately 6 months of a quit attempt), and sustained cessation (i.e. no restarting smoking within approximately 12 months of a quit attempt). Using the Aalen-Johansen estimator, we estimated the cumulative probability of achieving each step, accounting for the competing risk of death., Results: Forty-five percent of smokers attempted to quit, 27% achieved initial cessation, and 14% achieved sustained cessation with no differences by HIV status. Women with some post-high school education were more likely to achieve each step than those with less education. Outcomes did not differ by race. Thirty-six percent [95% confidence interval (95% CI): 31-42] of uninsured women attempted to quit compared with 47% (95% CI: 44-50) with Medicaid and 49% (95% CI: 41-59) with private insurance., Conclusion: To decrease smoking among USA women with and without HIV, targeted, multistage interventions, and increased insurance coverage are needed to address shortfalls along this cascade., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Violence and HIV/AIDS syndemic highly prevalent among women impairs HIV prevention efforts. Prolonged exposure to violence results in physical trauma and psychological distress. Building on previous findings regarding genital immune dysregulation following sexual abuse exposure, we investigate here whether systemic changes occur as well., Methods: Using the Women's Interagency HIV Study repository, 77 women were stratified by HIV serostatus and categorized into four subgroups: (1) no sexual abuse history and lower depression score (Control); (2) no sexual abuse history but higher depression score (Depression); (3) high sexual abuse exposure and lower depression score (Abuse); (4) high sexual abuse exposure and higher depression score (Abuse + Depression). Inflammation-associated immune biomarkers (TNF-α, IL-6, IL-1α, IL-1β, TGF-β, MIP-3α, IP-10, MCP-1, and Cathepsin-B) and anti-inflammatory/anti-HIV biomarkers (Secretory leukocyte protease inhibitor, Elafin, human beta-defensin-2 (HBD-2), alpha-defensins 1-3, Thrombospondin, Serpin-A1, and Cystatin-C) were measured in plasma using enzyme-linked immunosorbent assay. Within each HIV serostatus, differences in biomarker levels between subgroups were evaluated with Kruskal-Wallis and Dunn's test with Bonferroni correction. Spearman correlations between biomarkers were assessed for each subgroup., Results: Compared to the Control and Depression groups, Abuse + Depression was associated with significantly higher levels of chemokines MIP-3α and IP-10 (p < 0.01) and lower levels of inflammatory cytokine IL-1β (p < 0.01) in the HIV-uninfected population. Human beta-defensin-2 was lowest in the Abuse + Depression group (p < 0.05 versus Depression). By contrast, among HIV-infected, Abuse and Abuse + Depression were associated with lower levels of MIP-3α (p < 0.05 versus Control) and IP-10 (p < 0.05, Abuse versus Control). Inflammatory cytokine IL-6 was higher in both Abuse groups (p < 0.05 versus Control), while Elafin was lowest in the Abuse + Depression group (p < 0.01 versus Depression)., Conclusion: We report compromised plasma immune responses that parallel previous findings in the genital mucosa, based on sexual abuse and HIV status. Systemic biomarkers may indicate trauma exposure and impact risk of HIV acquisition/transmission.

Objectives: This study describes prevention behavior and psychosocial health among people living with HIV (PLHIV) and HIV-negative people during the early wave of the coronavirus disease 2019 (COVID-19) pandemic in the United States. We assessed differences by HIV status and associations between social disruption and psychosocial health., Design: A cross-sectional telephone/videoconference administered survey of 3411 PLHIV and HIV-negative participants in the Multicenter AIDS Cohort Study/WIHS Combined Cohort Study (MWCCS)., Methods: An instrument combining new and validated measures was developed to assess COVID-19 prevention efforts, social disruptions (loss of employment, childcare, health insurance, and financial supports), experiences of abuse, and psychosocial health. Interviews were performed between April and June 2020. Associations between social disruptions and psychosocial health were explored using multivariable logistic regression, adjusting for sociodemographics and HIV status., Results: Almost all (97.4%) participants reported COVID-19 prevention behavior; 40.1% participants reported social disruptions, and 34.3% reported health care appointment disruption. Men living with HIV were more likely than HIV-negative men to experience social disruptions (40.6% vs. 32.9%; P < 0.01), whereas HIV-negative women were more likely than women with HIV to experience social disruptions (51.1% vs. 39.8%, P < 0.001). Participants who experienced ≥2 social disruptions had significantly higher odds of depression symptoms [aOR = 1.32; 95% confidence interval (CI): 1.12 to 1.56], anxiety (aOR = 1.63; 95% CI: 1.17 to 2.27), and social support dissatisfaction (aOR = 1.81; 95% CI: 1.26 to 2.60)., Conclusions: This study builds on emerging literature demonstrating the psychosocial health impact related to the COVID-19 pandemic by providing context specific to PLHIV. The ongoing pandemic requires structural and social interventions to decrease social disruption and address psychosocial health needs among the most vulnerable populations., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Research has shown inconsistent patterns of patients' HIV serostatus disclosure to their dentists. Common barriers to disclosure have included confidentiality concerns, fear of treatment refusal, and discrimination. This study evaluated the prevalence of HIV serostatus disclosure to the dentist, whether the frequency of dental care utilization is associated with disclosure, and reasons for nondisclosure among women living with HIV., Methods: We administered a cross-sectional oral health survey to 1,526 women living with HIV in the Women's Interagency HIV Study including questions regarding HIV serostatus disclosure to dentists. Logistic regression models were used to analyze the association between dental care utilization (at least annually versus less than annually) and HIV serostatus disclosure to dentists., Results: Overall, 83 percent of women reported that they disclosed their HIV serostatus to their dentist. The most common reasons for nondisclosure were: a) the dentist did not ask, b) believing that the dentist did not need to know, and c) not having a consistent dentist. In the multivariable logistic regression model, at least annual dental care utilization, compared to less than annual, led to a 59 percent reduction in the odds of HIV nondisclosure to the dentist., Discussion: Study findings highlight that dentists who see their patients infrequently should consider methods for overcoming barriers to HIV nondisclosure and the possibility that their patient's HIV serostatus is undisclosed. Educating women living with HIV about how disclosure to dentists is a critical component of their dental assessment and treatment, and how preventive dental treatment can improve overall health outcomes, is important., (© 2020 American Association of Public Health Dentistry.)

Stigma in health care settings can have negative consequences on women living with HIV, such as increasing the likelihood of missed visits and reducing trust in their clinical providers. Informed by prior stigma research and considering knowledge gaps related to the effect of patient-provider race concordance, we conducted this study to assess if patient-provider race concordance moderates the expected association between HIV-related stigma in health care settings and patients' trust in their providers. Moderation analyses were conducted using Women's Interagency HIV Study data ( N  = 931). We found significant main effects for patient-provider race concordance. Higher experienced stigma was associated with lower trust in providers in all patient-provider race combinations [White-White: B  = -0.89, standard error (SE) = 0.14, p  = 0.000, 95% confidence interval, CI (-1.161 to -0.624); Black patient-White provider: B  = -0.19, SE = 0.06, p  = 0.003, 95% CI (-0.309 to -0.062); and Black-Black: B  = -0.30, SE = 0.14, p  = 0.037, 95% CI (-0.575 to -0.017)]. Higher anticipated stigma was also associated with lower trust in providers [White-White: B  = -0.42, SE = 0.07, p  = 0.000, 95% CI (-0.552 to -0.289); Black patient-White provider: B  = -0.17, SE = 0.03, p  = 0.000, 95% CI (-0.232 to -0.106); and Black-Black: B  = -0.18, SE = 0.06, p  = 0.002, 95% CI (-0.293 to -0.066)]. Significant interaction effects indicated that the negative associations between experienced and anticipated HIV-related stigma and trust in providers were stronger for the White-White combination compared with the others. Thus, we found that significant relationships between HIV-related experienced and anticipated stigma in health care settings and trust in providers exist and that these associations vary across different patient-provider race combinations. Given that reduced trust in providers is associated with antiretroviral medication nonadherence and higher rates of missed clinical visits, interventions to address HIV-related stigma in health care settings may improve continuum of care outcomes.

Background: Prior studies suggest neighborhood poverty and deprivation are associated with adverse health outcomes including death, but evidence is limited among persons with HIV, particularly women. We estimated changes in mortality risk from improvement in three measures of area-level socioeconomic context among participants of the Women's Interagency HIV Study., Methods: Starting in October 2013, we linked geocoded residential census block groups to the 2015 Area Deprivation Index (ADI) and two 2012-2016 American Community Survey poverty variables, categorized into national tertiles. We used parametric g-computation to estimate, through March 2018, impacts on mortality of improving each income or poverty measure by one and two tertiles maximum versus no improvement., Results: Of 1596 women with HIV (median age 49), 91 (5.7%) were lost to follow-up and 83 (5.2%) died. Most women (62%) lived in a block group in the tertile with the highest proportions of individuals with income:poverty <1; 13% lived in areas in the tertile with the lowest proportions. Mortality risk differences comparing a one-tertile improvement (for those in the two highest poverty tertiles) in income:poverty <1 versus no improvement increased over time; the risk difference was -2.2% (95% confidence interval [CI] = -3.7, -0.64) at 4 years. Estimates from family income below poverty level (-1.0%; 95% CI = -2.7, 0.62) and ADI (-1.5%; 95% CI = -2.8, -0.21) exposures were similar., Conclusions: Consistent results from three distinct measures of area-level socioeconomic environment support the hypothesis that interventions to ameliorate neighborhood poverty or deprivation reduce mortality risk for US women with HIV. See video abstract at, http://links.lww.com/EDE/B863., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Novel urine biomarkers have enabled the characterization of kidney tubular dysfunction and injury among persons living with HIV, a population at an increased risk of kidney disease. Even though several urine biomarkers predict progressive kidney function decline, antiretroviral toxicity, and mortality in the setting of HIV infection, the relationships among the risk factors for chronic kidney disease (CKD) and urine biomarkers are unclear., Methods: We assessed traditional and infection-related CKD risk factors and measured 14 urine biomarkers at baseline and at follow-up among women living with HIV in the Women's Interagency Health Study (WIHS). We then used simultaneously adjusted multivariable linear regression models to evaluate the associations of CKD risk factors with longitudinal changes in biomarker levels., Results: Of the 647 women living with HIV in this analysis, the majority (67%) were Black, the median age was 45 years and median follow-up time was 2.5 years. Each traditional and infection-related CKD risk factor was associated with a unique set of changes in urine biomarkers. For example, baseline hemoglobin a1c was associated with worse tubular injury (higher interleukin [IL]-18), proximal tubular reabsorptive dysfunction (higher α1-microglobulin), tubular reserve (lower uromodulin) and immune response to injury (higher chitinase-3-like protein-1 [YKL-40]). Furthermore, increasing hemoglobin a1c at follow-up was associated with further worsening of tubular injury (higher kidney injury molecule-1 [KIM-1] and IL-18), as well as higher YKL-40. HCV co-infection was associated with worsening proximal tubular reabsorptive dysfunction (higher β2-microglobulin [β2m]), and higher YKL-40, whereas HIV viremia was associated with worsening markers of tubular and glomerular injury (higher KIM-1 and albuminuria, respectively)., Conclusions: CKD risk factors are associated with unique patterns of biomarker changes among women living with HIV, suggesting that serial measurements of multiple biomarkers may help in detecting and monitoring kidney disease in this setting., (© 2021. The Author(s).)

In 2019, the National Institutes of Health combined the Multicenter AIDS Cohort Study (MACS) and the Women's Interagency HIV Study (WIHS) into the MACS/WIHS Combined Cohort Study (MWCCS). In this paper, participants who made a study visit during October 2018-September 2019 (targeted for MWCCS enrollment) are described by human immunodeficiency virus (HIV) serostatus and compared with people living with HIV (PLWH) in the United States. Participants include 2,115 women and 1,901 men with a median age of 56 years (interquartile range, 48-63); 62% are PLWH. Study sites encompass the South (18%), the Mid-Atlantic/Northeast (45%), the West Coast (22%), and the Midwest (15%). Participant race/ethnicity approximates that of PLWH throughout the United States. Longitudinal data and specimens collected for 35 years (men) and 25 years (women) were combined. Differences in data collection and coding were reviewed, and key risk factor and comorbidity data were harmonized. For example, recent use of alcohol (62%) and tobacco (28%) are common, as are dyslipidemia (64%), hypertension (56%), obesity (42%), mildly or severely impaired daily activities (31%), depressive symptoms (28%), and diabetes (22%). The MWCCS repository includes serum, plasma, peripheral blood mononuclear cells, cell pellets, urine, cervicovaginal lavage samples, oral samples, B-cell lines, stool, and semen specimens. Demographic differences between the MACS and WIHS can confound analyses by sex. The merged MWCCS is both an ongoing observational cohort study and a valuable resource for harmonized longitudinal data and specimens for HIV-related research., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2021. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Our objective was to examine the association between healthcare payer type and missed HIV care visits among 1,366 US women living with HIV (WLWH) enrolled in the prospective Women's Interagency HIV Study (WIHS). We collected secondary patient-level data (October 1, 2017-September 30, 2018) from WLWH at nine WIHS sites. We used bivariate and multivariable binary logistic regression to examine the relationship between healthcare payer type (cross-classification of patients' ADAP and health insurance enrollment) and missed visits-based retention in care, defined as no-show appointments for which patients did not reschedule. Our sample included all WLWH who self-reported having received HIV care at least once during the two consecutive biannual WIHS visits a year prior to October 1, 2017-September 30, 2018. In the bivariate model, compared to uninsured WLWH without ADAP, WLWH with private insurance + ADAP were more likely to be retained in care, as were WLWH with Medicaid only and private insurance only. In the adjusted model, WLWH with private insurance only were more likely to be retained in care compared to uninsured WLWH without ADAP. Private health insurance and ADAP are associated with increased odds of retention in care among WLWH.

Background: People with HIV are disproportionately coinfected with hepatitis C virus (HCV) and experience accelerated liver-related mortality. Direct-acting antivirals (DAAs) yield high sustained virologic response (SVR) rates, but uptake is suboptimal. This study characterizes the DAA-era HCV treatment cascade and barriers among US men and women with or at risk for HIV., Methods: We constructed HCV treatment cascades using the Women's Interagency HIV Study (women, 6 visits, 2015-2018, n = 2447) and Multicenter AIDS Cohort Study (men, 1 visit, 2015-2018, n = 2221). Cascades included treatment-eligible individuals (ie, HCV RNA-positive or reported DAAs). Surveys captured self-reported clinical (eg, CD4), patient (eg, missed visits), system (eg, appointment access), and financial/insurance barriers., Results: Of 323/92 (women/men) treatment eligible, most had HIV (77%/70%); 69%/63% were black. HIV-positive women were more likely to attain cascade outcomes than HIV-negative women (39% vs 23% initiated, 21% vs 12% SVR); similar discrepancies were noted for men. Black men and substance users were treated less often. Women initiating treatment (vs not) reported fewer patient barriers (14%/33%). Among men not treated, clinical barriers were prevalent (53%)., Conclusions: HIV care may facilitate HCV treatment linkage and barrier navigation. HIV-negative individuals, black men, and substance users may need additional support., Clinical Trials Registration: NCT00000797 (Women's Interagency HIV Study); NCT00046280 (Multicenter AIDS Cohort Study)., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: Frailty is frequently observed among people with HIV, and food insecurity is associated with frailty in the general population. Evidence is scarce on the associations between food insecurity and frailty among women with HIV who may be particularly vulnerable to the impacts of food insecurity. The goal of this study was to assess associations between food insecurity and frailty among women with and without HIV., Methods: There were 1265 participants from the Women's Interagency HIV Study who participated in frailty assessments in 2017. Frailty was measured using the Fried Frailty Phenotype, and women were subsequently categorized as robust, pre-frail or frail. Food insecurity was assessed using the U.S. Household Food Security Survey Module, with women categorized as having high, marginal, low or very low food security. Multinomial logistic regression models were conducted to examine cross-sectional associations between food insecurity and frailty while adjusting for socio-demographic, behavioural and HIV status covariates., Results and Discussion: Approximately one-third (31.9%) of the women had marginal, low or very low food security, and the proportions of women who met the criteria for frailty or pre-frailty were 55.6% and 12.4% respectively. In the adjusted model, the relative risk ratio (RRR) of frailty for women with very low food security versus women with high food security was 3.37 (95% CI [1.38 to 8.24], p < 0.01); the corresponding RRR of pre-frailty was 3.63 (95% CI [1.76 to 7.51], p < 0.001). Higher annual household income was associated with lower RRRs of frailty or pre-frailty (p < 0.01). Similarly, older age was associated with more frequent frailty (RRR=1.06, 95% CI [1.03 to 1.09], p < 0.001). HIV serostatus was not significantly associated with either pre-frailty (RRR=0.97, 95% CI [0.71 to 1.31]) or frailty (RRR=0.75, 95% CI [0.48 to 1.16])., Conclusions: Very low food security was associated with more frequent frailty and pre-frailty among women with and without for HIV. HIV serostatus was not associated with frailty., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: To estimate the incidence, prevalence, frequency, and duration of incarceration and to identify risk factors for incarceration among women at risk for human immunodeficiency virus (HIV) in the United States. Methods: During semiannual study visits in a multicenter cohort study, 970 HIV sero-negative participants at risk for HIV were asked about their own incarceration (10/2007-09/2017) and incarceration of sexual partners (10/2013-09/2017). We used descriptive statistics and multivariable log-binomial regression to identify baseline predictors of incident incarceration. Results: Median follow-up time across the 970 participants was 5.5 years (IQR 3.5-9.5). Nearly half ( n  = 453, 46.7%) of participants were incarcerated during or before the study, and the incarceration rate was 5.5 per 100 person-years. In multivariable models, incident incarceration was associated with prior incarceration (RR 5.20, 95% CI: 3.23-8.41) and noninjection drug use (RR 1.57, 95% CI: 1.10-2.25). Conclusions: Incarceration is common for women at risk for HIV. Prevention interventions that address the complex interplay of drug use, sex exchange, and housing instability for women who have experienced incarceration have the potential to reach an important group of U.S. women at risk of HIV infection.

Rationale & Objective: Single measurements of urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in HIV infection, but the prognostic value of repeat measurements over time is unknown., Study Design: Cohort study., Setting & Participants: 647 women living with HIV infection enrolled in the Women's Interagency Health Study., Exposures: 14 urinary biomarkers of kidney tubule health measured at 2 visits over a 3-year period., Outcome: Incident CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m 2 at two 6-month visits and an average eGFR decline ≥ 3% per year., Analytical Approach: We used multivariable generalized estimating equations adjusting for CKD risk factors to evaluate baseline, time-updated, and change-over-time biomarker associations with incident CKD. We compared CKD discrimination between models with and without a parsimoniously selected set of biomarkers., Results: During a median 7 years of follow-up, 9.7% (63/647) developed CKD. In multivariable-adjusted analyses, 3 of 14 baseline biomarkers associated with incident CKD. In contrast, 10 of 14 time-updated biomarkers and 9 of 14 biomarkers modeled as change over time associated with incident CKD. Urinary epidermal growth factor (EGF), α 1 -microglobulin (A1M), and albumin were selected using penalized regression methods. In the time-updated model, lower urinary EGF (risk ratio [RR] per 2-fold higher time-updated biomarker levels, 0.69; 95% CI, 0.58-0.81), higher urinary A1M (RR, 1.47; 95% CI, 1.25-1.73), and higher urinary albumin excretion (RR, 1.21; 95% CI, 1.03-1.42) were jointly associated with increased risk for CKD. Compared with a base model (C statistic, 0.75), CKD discrimination improved after adding urinary EGF, A1M, and albumin values across baseline (C = 0.81), time-updated (C = 0.83), and change-over-time (C = 0.83) models ( P  < 0.01 for all)., Limitations: Observational design, incident CKD definition limited to eGFR., Conclusions: Repeat urinary biomarker measurements for kidney tubule health have stronger associations with incident CKD compared with baseline measurements and moderately improve CKD discrimination in women living with HIV infection., (© 2021 The Authors.)