Women's Interagency HIV Study Research Articles

Examining the relationships between pain symptoms and psychosocial functioning among women living with and at risk for human immunodeficiency virus using a cross-sectional psychological network analysis.

Pain is prevalent among women living with HIV (WLWH); however, research on pain experience among WLWH in the United States is limited. This study used a network analysis to simultaneously examine the relationships between pain experience and psychosocial functioning among WLWH and human immunodeficiency virus (HIV)-negative women. A secondary analysis of public data from the Women's Interagency HIV Study, a U.S. longitudinal cohort study of the experiences of WLWH and women at increased risk for HIV (HIV negative), was completed. Data were from Visit 42 in 2015 and included 451 WLWH and 194 HIV-negative women who endorsed experiencing pain in the week prior to the interview. Similar to the sociodemographic characteristics of WLWH in the United States, the majority of women in the sample were racially and/or ethnically minoritized and of low socioeconomic position. Networks were modeled using measures of pain intensity, pain interference, depression symptoms, anxiety/worry symptoms, meaning in life, and emotional support. Network models for WLWH and HIV-negative women were comparable (ps > .05). Depression symptoms were a central construct (strength = 1.82 and 1.77, respectively) within the networks, and pain interference was associated with psychosocial constructs (ps < .05), while pain intensity was not (ps > .05). Meaning in life and emotional support were not directly associated with pain (ps > .05). Network findings suggest that reducing depression symptoms may result in improved pain experience and broader positive impact for WLWH and for women at increased risk of HIV. This finding is consistent with research with other pain-focused populations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Substance use and menopausal symptoms among people with and without HIV in the US, 2008-2020.

The aim of the study is to assess associations between substance use and menopausal symptoms among US people living with and without HIV in a longitudinal cohort. We analyzed self-reported menopausal symptoms and substance use from biannual Women's Interagency HIV Study (WIHS) visits from 2008-2020. Substance use since the last visit or lifetime cumulative use included tobacco, alcohol, marijuana, crack/cocaine, and opioids. Logistic regression quantified associations between each substance use and menopausal symptom frequency (vasomotor, mood, and musculoskeletal), adjusting for other substance use, HIV status, demographics, comorbidities, and trauma. A total of 1,949 participants contributed early perimenopausal, late perimenopausal, or postmenopausal study visits. Across reproductive-aging stages, based on menstrual history, and among participants with and without HIV, participants reported frequent vasomotor (range 22-43%), mood (18-28%), and musculoskeletal (25-34%) symptoms. Many reported ever using tobacco (72%), heavy alcohol (75%), marijuana (73%), crack (50%), and opioids (31%). Current heavy alcohol use (odds ratio [OR]: 1.22; 95% confidence interval [CI]: 1.10-1.37), cumulative marijuana use (OR: 1.15, 95% CI: 1.01-1.32), and cumulative tobacco use (OR: 1.06, 95% CI: 1.01-1.12) were associated with a higher frequency of vasomotor symptoms; current heavy alcohol use (OR: 1.20, 95% CI: 1.04-1.39) and current opioid use (OR: 1.13; 95% CI: 1.01-1.25) were associated with mood symptoms; and current opioid use (OR: 1.11, 95% CI: 1.00-1.23) was associated with musculoskeletal symptoms. All other associations were found to be null. Current and prior substance use may independently affect symptoms experienced during the menopausal transition and may indicate potential to benefit from additional intervention and referral to menopause specialty care.

Intact HIV Reservoir in Monocytes Is Associated With Cognitive Function in Virally Suppressed Women With HIV

Abstract Background Monocytes are susceptible to human immunodeficiency virus (HIV) infection, form HIV reservoirs, and contribute to central nervous system complications (eg, cognitive impairment) in virally suppressed women with HIV (vsWWH). However, it remains unknown if the quality and/or quantity of the monocyte reservoir contributes to cognition in vsWWH. Methods Sixty-two vsWWH (mean age = 56.1 years, SD = 7.1; 93% Black, non-Hispanic; all HIV RNA &amp;lt;250 copies/mL) completed a cognitive test battery, blood draw, and whole-blood immunophenotyping. Monocytes and CD4 T cells were isolated from a subset of 53 participants and the HIV reservoir was assessed using cell-specific intact proviral DNA assays (IPDA). Demographically adjusted z-scores were calculated for each outcome using data from participants without HIV in the Women's Interagency HIV Study. Cognitive outcomes of interest included domain-specific and global z-scores. Results Thirty-Eight percent of vsWWH had detectable intact HIV genomes in monocytes (median = 21.5 copies/million). Higher levels of intact HIV genomes per million monocytes were associated with poorer verbal memory (delayed recall, r = 0.55, P = .01; recognition, r = 0.46, P = .04), fine motor skills (r = 0.50, P = .03), and global function (r = 0.47, P = .04). Higher levels of intact HIV genomes in monocytes were associated with percent intermediate monocytes (r = 0.60, P = .008), and the ratio of intact per intermediate monocyte was associated with worse memory (r = −0.59, P = .008). There were no associations between CD4 reservoir and cognition. Conclusions The number of intact HIV genomes per million monocytes was related to poorer cognition and the percentage of intermediate monocytes. These findings suggest that the presence of HIV genomes in general do not relate to cognitive complications, but intact, and therefore potentially replication-competent HIV, may contribute to cognitive complications in vsWWH.

Consequences of low-level viremia among women with HIV in the United States.

Investigate the outcomes of women with HIV (WWH) with low-level viremia (LLV). The prevalence of LLV and potential clinical sequelae, such as virologic failure and non-AIDS comorbidity (NACM) development, are poorly characterized among WWH. We analyzed data from the Women's Interagency HIV Study among WWH enrolled from 2003 to 2020 who reported antiretroviral therapy use at least 1 year followed by an HIV-1 viral load less than 200 copies/ml. Consecutive viral load measurements from four semi-annual visits were used to categorize women at baseline as having: virologic suppression (all viral load undetectable), intermittent LLV (iLLV; nonconsecutive detectable viral load up to 199 copies/ml), persistent LLV (pLLV; at least two consecutive detectable viral load up to 199 copies/ml), or virologic failure (any viral load ≥200 copies/ml). Adjusted hazard ratios quantified the association of virologic category with time to incident virologic failure and multimorbidity (≥2 of 5 NACM) over 5-year follow-up. Of 1598 WWH, baseline median age was 47 years, 64% were Black, 21% Hispanic, and median CD4 + cell count was 621 cells/μl. After excluding 275 women (17%) who had virologic failure at baseline, 58, 19, and 6% were categorized as having virologic suppression, iLLV, and pLLV, respectively. Compared with WWH with virologic suppression, the adjusted hazard ratio [aHR; 95% confidence interval (CI)] for incident virologic failure was 1.88 (1.44-2.46) and 2.51 (1.66-3.79) for iLLV and pLLV, respectively; and the aHR for incident multimorbidity was 0.81 (0.54-1.21) and 1.54 (0.88-2.71) for iLLV and pLLV, respectively. Women with iLLV and pLLV had an increased risk of virologic failure. Women with pLLV had a trend towards increased multimorbidity risk.

Exploring the role of motherhood in healthcare engagement for women living with HIV in the USA

Mothers living with HIV are faced with managing their own complex healthcare and wellness needs while caring for their children. Understanding the lived experiences of mothers living with HIV, including grandmothers and mothers with older children - who are less explicitly represented in existing literature, may guide the development of interventions that best support them and their families. This study sought to explore the role of motherhood and related social/structural factors on engagement with HIV care, treatment-seeking behaviour, and overall HIV management among mothers living with HIV in the USA to inform such efforts. Semi-structured interviews were conducted between June and December 2015 with 52 mothers living with HIV, recruited from the Women’s Interagency HIV Study (WIHS) sites in four US cities. Five broad themes were identified from the interviews: children as a motivation for optimal HIV management; children as providing logistical support for HIV care and treatment; the importance of social support for mothers; stressors tied to responsibilities of motherhood; and stigma about being a mother living with HIV. Findings underscore the importance of considering the demands of motherhood when developing more effective strategies to support mothers in managing HIV and promoting the overall health and well-being of their families.

Tryptophan-Kynurenine Pathway Activation and Cognition in Virally Suppressed Women With HIV.

Immune and cognitive dysfunction persists even in virally suppressed women with HIV (VS-WWH). Since inflammation and HIV proteins induce the enzyme indoleamine 2,3-dioxygenase (IDO), converting tryptophan (T) to kynurenine (K) while producing downstream neurotoxic metabolites, we investigated IDO activation (KT ratio) in relation to cognition in VS-WWH and demographically similar women without HIV (WWoH). Ninety-nine VS-WWH on stable antiretroviral therapy and 102 WWoH (median age 52 vs 54 years; 73% vs 74% Black, respectively) from the New York and Chicago sites of the Women's Interagency HIV Study (WIHS) completed a neuropsychological test battery assessing motor function, processing speed, attention/working memory, verbal fluency, verbal learning and memory, and executive function and had plasma measured for tryptophan-kynurenine metabolites through liquid chromatography-tandem mass spectrometry and monocyte-derived [soluble cluster of differentiation-14 (sCD14), soluble cluster of differentiation-163 (sCD163), monocyte chemoattractant protein-1 (MCP-1)] plus general inflammatory markers [tumor necrosis factor alpha-2 receptor (TNF-R2), high-sensitivity C-reactive protein, high-sensitivity interleukin-6] through enzyme-linked immunosorbent assays between 2017 and 2020. VS-WWH had a higher KT ratio (P < 0.01) and higher sCD14 levels (P < 0.05) compared with WWoH. Higher sCD163 was associated with higher KT ratio (R = 0.29, P < 0.01) and worse fine motor function in VS-WWH; after adjusting for sCD163 and sCD14 in multivariable regressions, higher KT ratio remained significantly associated with impaired fine motor function in VS-WWH only (standardized β = -0.29, P < 0.05). IDO activation was not associated with cognition in WWoH. IDO activation (K:T) was associated with worse fine motor control in VS-WWH independent of measured systemic inflammation. Further studies investigating biological mechanisms linking IDO activation to fine motor function among VS-WWH are warranted.

Menopause and Estrogen Associations With Gut Barrier, Microbial Translocation, and Immune Activation Biomarkers in Women With and Without HIV.

Estrogens may protect the gut barrier and reduce microbial translocation and immune activation, which are prevalent in HIV infection. We investigated relationships of the menopausal transition and estrogens with gut barrier, microbial translocation, and immune activation biomarkers in women with and without HIV. Longitudinal and cross-sectional studies nested in the Women's Interagency HIV Study. Intestinal fatty acid binding protein, lipopolysaccharide binding protein, and soluble CD14 (sCD14) levels were measured in serum from 77 women (43 with HIV) before, during, and after the menopausal transition (∼6 measures per woman over ∼13 years). A separate cross-sectional analysis was conducted among 72 postmenopausal women with HIV with these biomarkers and serum estrogens. Women in the longitudinal analysis were a median age of 43 years at baseline. In piecewise, linear, mixed-effects models with cutpoints 2 years before and after the final menstrual period to delineate the menopausal transition, sCD14 levels increased over time during the menopausal transition (Beta [95% CI]: 38 [12 to 64] ng/mL/yr, P = 0.004), followed by a decrease posttransition (-46 [-75 to -18], P = 0.001), with the piecewise model providing a better fit than a linear model (P = 0.0006). In stratified analyses, these results were only apparent in women with HIV. In cross-sectional analyses, among women with HIV, free estradiol inversely correlated with sCD14 levels (r = -0.26, P = 0.03). Lipopolysaccharide binding protein and intestinal fatty acid binding protein levels did not appear related to the menopausal transition and estrogen levels. Women with HIV may experience heightened innate immune activation during menopause, possibly related to the depletion of estrogens.

Awareness, treatment, and control of hypertension among women at risk or living with HIV in the US South.

Timely control of hypertension is vital to prevent comorbidities. We evaluated the association of race/ethnicity and HIV infection with incident hypertension outcomes, including awareness, treatment, and control. We evaluated cisgender women living with HIV and sociodemographically matched women living without HIV recruited into four Southern sites of the Women's Interagency HIV Study (WIHS) (2013-2019). We calculated measurements of the time to four events or censoring: incident hypertension, hypertension awareness, hypertension treatment, and hypertension control. Hazard ratios for race/ethnicity and HIV status were calculated for each outcome using Cox proportional-hazards models adjusted for sociodemographic, behavioral, and clinical risk factors. Among 712 women, 56% were hypertensive at baseline. Forty-five percentage of the remaining women who were normotensive at baseline developed incident hypertension during follow-up. Non-Hispanic white and Hispanic women had faster time to hypertension control compared with non-Hispanic black women ( P = 0.01). In fully adjusted models, women living with HIV who were normotensive at baseline had faster time to treatment compared with normotensive women living without HIV ( P = 0.04). In our study of women in the US South, non-Hispanic black women became aware of their hypertension diagnosis more quickly than non-Hispanic white and Hispanic women but were slower to control their hypertension. Additionally, women living with HIV more quickly treated and controlled their hypertension compared with women living without HIV.

Genetic predictors for bacterial vaginosis in women living with and at risk for HIV infection.

Bacterial vaginosis (BV) disproportionally impacts Black and Hispanic women, placing them at risk for HIV, sexually transmitted infections and preterm birth. It is unknown whether there are differences by genetic ancestry in BV risk or whether polymorphisms associated with BV risk differ by ancestry. Women's Interagency HIV Study (WIHS) participants with longitudinal Nugent scores were dichotomized as having (n=319, Nugent 7-10) or not having BV (n=367, Nugent 0-3). Genetic ancestry was defined by clustering of principal components from ancestry informative markers and further stratified by BV status. 627 single nucleotide polymorphisms (SNPs) across 41 genes important in mucosal defense were identified in the WIHS GWAS. A logistic regression analysis was adjusted for nongenetic predictors of BV and self-reported race/ethnicity to assess associations between genetic ancestry and genotype. Self-reported race and genetic ancestry were associated with BV risk after adjustment for behavioral factors. Polymorphisms in mucosal defense genes including syndecans, cytokines and toll-like receptors (TLRs) were associated with BV in all ancestral groups. The common association of syndecan, cytokine and TLR genes and the importance of immune function and inflammatory pathways in BV, suggests these should be targeted for further research on BV pathogenesis and therapeutics.

DNA methylation-based telomere length is associated with HIV infection, physical frailty, cancer, and all-cause mortality.

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.

Association of Androgen Hormones, Sex Hormone-Binding Globulin, and the Menopausal Transition With Incident Diabetes Mellitus in Women With and Without HIV.

HIV is associated with alterations in androgen hormone levels and sex hormone-binding globulin (SHBG) in women. Higher SHBG has been associated with a lower risk of diabetes in the general population, but the contribution of HIV, androgen hormones, SHBG, and menopausal phase to diabetes is unclear. From April 2003 through February 2020, 896 women with HIV (WWH) and 343 women without HIV (WWOH) from the Women's Interagency HIV Study with morning total testosterone, dehydroepiandrosterone sulfate (DHEAS), and SHBG levels were followed to assess for incident diabetes. Parametric regression models were used with age as the time scale and relative times (RT) as the measure of association of hormone level and menopausal phase with incident diabetes. Analyses incorporated time-dependent androgen hormone, SHBG levels, and menopausal phase and were adjusted for race/ethnicity, enrollment year, smoking status, BMI, hepatitis C virus status, and HIV-related factors. In total, 128 (14%) WWH and 47 (14%) WWOH developed diabetes. In WWH, a doubling of SHBG and DHEAS were associated with a 7% (RT = 1.07 [95% CI: 0.82 to 1.40] and 15% (RT = 1.15 [95% CI: 0.95 to 1.39]) longer time to diabetes, respectively; in WWOH, a doubling of SHBG and DHEAS were associated with 84% (RT = 1.84 [95% CI: 0.89 to 3.82]) and 41% (RT= 1.41 [95% CI: 0.82 to 2.44]) longer times to diabetes. Total testosterone was not associated. In WWH, later menopausal phase was associated with shorter times to diabetes. Despite alterations in androgen hormone and SHBG levels in HIV, regardless of HIV status, higher SHBG and DHEAS were associated with nonstatistically significant slower progression to diabetes. The menopausal transition may be a better hormonal indicator of diabetes risk in WWH.

Microbial Translocation and Gut Damage Are Associated With an Elevated Fast Score in Women Living With and Without HIV.

Steatohepatitis is common in persons living with HIV and may be associated with gut microbial translocation (MT). However, few studies have evaluated the gut-liver axis in persons living with HIV. In the Women's Interagency HIV Study, we examined the associations of HIV and circulating biomarkers linked to MT and gut damage using the FibroScan-aspartate aminotransferase (FAST) score, a noninvasive surrogate for steatohepatitis with advanced fibrosis. Among 883 women with HIV and 354 without HIV, we used multivariable regression to examine the associations of HIV and serum biomarkers linked to MT and gut damage (kynurenine and tryptophan ratio, intestinal fatty acid-binding protein, soluble CD14, and soluble CD163) with a log-transformed FAST score after adjusting for key covariates. We used a path analysis and mediation models to determine the mediating effect of each biomarker on the association of HIV with FAST. HIV infection was associated with a 49% higher FAST score. MT biomarker levels were higher in women with HIV than women without HIV (P < .001 for each). MT biomarkers mediated 13% to 32% of the association of HIV and FAST score. Biomarkers linked to MT and gut damage are associated with a higher FAST score and mediate the association of HIV with a higher FAST score. Our findings suggest that MT may be an important mechanism by which HIV increases the risk of steatohepatitis with advanced fibrosis.

Brief Report: Substance Use Care Continuum in Women With and Without HIV in the Southern United States.

Substance use (SU) contributes to poor outcomes among persons living with HIV. Women living with HIV (WWH) in the United States are disproportionately affected in the South, and examining SU patterns, treatment, and HIV outcomes in this population is integral to addressing HIV and SU disparities. WWH and comparable women without HIV (WWOH) who enrolled 2013-2015 in the Women's Interagency HIV Study Southern sites (Atlanta, Birmingham/Jackson, Chapel Hill, and Miami) and reported SU (self-reported nonmedical use of drugs) in the past year were included. SU and treatment were described annually from enrollment to the end of follow-up. HIV outcomes were compared by SU treatment engagement. At enrollment, among 840 women (608 WWH, 232 WWOH), 18% (n = 155) reported SU in the past year (16% WWH, 24% WWOH); 25% (n = 38) of whom reported SU treatment. Over time, 30%, 21%, and 18% reported SU treatment at 1, 2, and 3 years, respectively, which did not significantly differ by HIV status. Retention in HIV care did not differ by SU treatment. Viral suppression was significantly higher in women who reported SU treatment only at enrollment ( P = 0.03). We identified a substantial gap in SU treatment engagement, with only a quarter reporting treatment utilization, which persisted over time. SU treatment engagement was associated with viral suppression at enrollment but not at other time points or with retention in HIV care. These findings can identify gaps and guide future strategies for integrating HIV and SU care for WWH.

HIV Interacts with Posttraumatic Stress Disorder to Impact Fear Psychophysiology in Trauma-Exposed Black Women.

The prevalence of posttraumatic stress disorder (PTSD) among people living with HIV (PLWH) is higher than in the general population and can impact health behaviors. The influence of HIV on PTSD psychophysiology requires further investigation due to implications for the treatment of PTSD in PLWH. Utilizing fear-potentiated startle (FPS), we aimed to interrogate the influence of PTSD and HIV on fear responses. Women (18-65 years of age) recruited from the Women's Interagency HIV Study in Atlanta, GA (n = 70, 26 without HIV and 44 with HIV), provided informed consent and completed a semistructured interview to assess trauma exposure and PTSD symptom severity. Participants also underwent an FPS paradigm to assess fear acquisition and extinction: Psychophysiological indices that measure how individuals learn new fear and then subsequently attempt to suppress this fear. Women with PTSD, who did not have HIV, exhibited a greater startle response compared to women without PTSD or HIV during late acquisition to both the danger cue, reinforced conditioned stimulus (CS+, p = 0.013)), and the safety cue, non-reinforced conditioned stimulus (CS-, p = 0.046)), whereas women living with HIV (WLH) and PTSD demonstrated blunted fear responses compared to women with PTSD only. During extinction, WLH comorbid with PTSD exhibited an increased fear response during the extinction period in comparison to all other groups (p = 0.023). Women without PTSD demonstrated a reduction in the fear response during extinction regardless of HIV status. Our findings indicate that HIV further modifies fear psychophysiology in WLH with comorbid PTSD, highlighting the importance of considering HIV status in conjunction with PTSD treatment.

Epigenetic Aging and Musculoskeletal Outcomes in a Cohort of Women Living With HIV.

The relationship between accelerated epigenetic aging and musculoskeletal outcomes in women with HIV (WWH) has not been studied. We measured DNA methylation age using the Infinium MethylationEPIC BeadChip in a cohort from the Women's Interagency HIV Study (n = 190) with measures of bone mineral density (BMD) and physical function. We estimated 6 biomarkers of epigenetic aging-epigenetic age acceleration (EAA), extrinsic EAA, intrinsic EAA, GrimAge, PhenoAge, and DNA methylation-estimated telomere length-and evaluated associations of epigenetic aging measures with BMD and physical function. We also performed epigenome-wide association studies to examine associations of DNA methylation signatures with BMD and physical function. This study included 118 WWH (mean age, 49.7 years; 69% Black) and 72 without HIV (mean age, 48.9 years; 69% Black). WWH had higher EAA (mean ± SD, 1.44 ± 5.36 vs -1.88 ± 5.07; P < .001) and lower DNA methylation-estimated telomere length (7.13 ± 0.31 vs 7.34 ± 0.23, P < .001) than women without HIV. There were no significant associations between accelerated epigenetic aging and BMD. Rather, measures of accelerated epigenetic aging were associated with lower physical function. Accelerated epigenetic aging was observed in WWH as compared with women without HIV and was associated with lower physical function in both groups.

A Bayesian approach for investigating the pharmacogenetics of combination antiretroviral therapy in people with HIV.

Combination antiretroviral therapy (ART) with at least three different drugs has become the standard of care for people with HIV (PWH) due to its exceptional effectiveness in viral suppression. However, many ART drugs have been reported to associate with neuropsychiatric adverse effects including depression, especially when certain genetic polymorphisms exist. Pharmacogenetics is an important consideration for administering combination ART as it may influence drug efficacy and increase risk for neuropsychiatric conditions. Large-scale longitudinal HIV databases provide researchers opportunities to investigate the pharmacogenetics of combination ART in a data-driven manner. However, with more than 30 FDA-approved ART drugs, the interplay between the large number of possible ART drug combinations and genetic polymorphisms imposes statistical modeling challenges. We develop a Bayesian approach to examine the longitudinal effects of combination ART and their interactions with genetic polymorphisms on depressive symptoms in PWH. The proposed method utilizes a Gaussian process with a composite kernel function to capture the longitudinal combination ART effects by directly incorporating individuals' treatment histories, and a Bayesian classification and regression tree to account for individual heterogeneity. Through both simulation studies and an application to a dataset from the Women's Interagency HIV Study, we demonstrate the clinical utility of the proposed approach in investigating the pharmacogenetics of combination ART and assisting physicians to make effective individualized treatment decisions that can improve health outcomes for PWH.

HIV, HIV-Specific Factors, and Myocardial Disease in Women.

People with human immunodeficiency virus (HIV) (PWH) have an increased risk of cardiovascular disease (CVD). Cardiac magnetic resonance (CMR) has documented higher myocardial fibrosis, inflammation, and steatosis in PWH, but studies have mostly relied on healthy volunteers as comparators and focused on men. We investigated the associations of HIV and HIV-specific factors with CMR phenotypes in female participants enrolled in the Women's Interagency HIV Study's New York and San Francisco sites. Primary phenotypes included myocardial native (n) T1 (fibro-inflammation), extracellular volume fraction (fibrosis), and triglyceride content (steatosis). Associations were evaluated with multivariable linear regression, and results pooled or meta-analyzed across centers. Among 261 women with HIV (WWH, N = 362), 76.2% had undetectable viremia at CMR. For the 82.8% receiving continuous antiretroviral therapy (ART) in the preceding 5 years, adherence was 51.7%, and 69.4% failed to achieve persistent viral suppression (40.7% with peak viral load <200 cp/mL). Overall, WWH showed higher nT1 than women without HIV after full adjustment. This higher nT1 was more pronounced in those with antecedent or current viremia or nadir CD4+ count <200 cells/μL, with the latter also associated with higher extracellular volume fraction. WWH and current CD4+ count <200 cells/μL had less cardiomyocyte steatosis. Cumulative exposure to specific ART showed no associations. Compared with sociodemographically similar women without HIV, WWH on ART exhibit higher myocardial fibro-inflammation, which is more prominent with unsuppressed viremia or CD4+ lymphopenia. These findings support the importance of improved ART adherence strategies, along with better understanding of latent infection, to mitigate cardiac end-organ damage in this population.

Co-Utilization of HIV, Substance Use, Mental Health Services Among Women With Current Substance Use: Opportunities for Integrated Care?

The syndemic of HIV, substance use (SU), and mental illness has serious implications for HIV disease progression among women. We described co-utilization of HIV care, SU treatment, and mental health treatment among women with or at risk for HIV. We included data from women with or at risk for HIV (n = 2559) enrolled in all 10 sites of the Women's Interagency HIV Study (WIHS) from 2013 to 2020. Current SU was defined as self-reported, non-medical use of drugs in the past year, excluding use of only marijuana. Tobacco and alcohol were assessed separately. We described co-utilization of SU treatment, tobacco and alcohol use treatment, HIV care, and mental health care in the past year among women who were eligible for each service. We compared service utilization by those who did/did not utilize SU treatment using Wald Chi-square tests. Among women with current SU (n = 358), 42% reported utilizing SU treatment. Among those with current SU+HIV (n = 224), 84% saw their HIV provider, and 34% saw a mental health provider. Among women with current SU+heavy alcohol use (n = 95), 18% utilized alcohol use treatment; among current SU+tobacco use (n = 276), 8% utilized tobacco use treatment. Women who utilized SU treatment had higher utilization of alcohol use treatment (59% vs. 5%; P < .001) and tobacco use treatment (12% vs. 5%; P = .028). HIV care engagement was high regardless of SU treatment. We found high engagement in SU and HIV care, but low engagement in alcohol and tobacco use treatment. Integrated SU treatment services for women, including tobacco/alcohol treatment and harm reduction, are needed to optimize treatment engagement and HIV care continuum outcomes.

"As I Grew Older, My Life Got Better": Conceptions of Successful Aging among Older Women Living with or at Risk of HIV.

Successful aging (SA) is an important target for HIV care. However, we have insufficient understanding of how older women living with HIV (OWLH) in the US define SA. We explored conceptions of SA by OWLH and older women at risk of HIV and examined whether SA conceptions differed by (1) HIV serostatus, and (2) participation in the Women's Interagency HIV Study (WIHS). These analyses were part of a larger mixed-methods study with a sequential design. Participants were recruited at two clinical WIHS sites. We enrolled both WIHS participants and non-WIHS clinic patients. Our sample was 84% Black and included 29 OWLH and 15 older women at risk of HIV. We conducted 21 semi-structured interviews and four focus groups. The dataset was analyzed using descriptive, comparative, and relational analysis. We found four interlinked themes: life course perspective, accepting and celebrating aging, taking care of yourself, and looking good. The life course perspective was a core theme: participants assessed their aging in comparison to their earlier life hardships. These themes were similarly present among OWLH and older women at risk of HIV, although OWLH emphasized taking care of HIV. SA conceptualizations by OWLH did not differ whether or not they participated in the WIHS. Women living with or at risk of HIV may experience severe hardships throughout their lives. Overcoming these hardships may be linked to SA. Assessing the needs and connecting women to resources and programs are critical for SA promotion.

Mediation analysis of chronic kidney disease risk factors using kidney biomarkers in women living with HIV.

Novel urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in persons living with HIV. However, it is unknown whether these biomarkers provide mechanistic insight into the associations between clinical risk factors for CKD and subsequent CKD risk. Among 636 women living with HIV in the Women's Interagency HIV Study with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m 2 , we used a counterfactual approach to causal mediation analysis to evaluate the extent to which systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin a1c (Hba1c) and serum albumin associations with incident CKD were mediated by eight urine proteins. These biomarkers reflect proximal tubular reabsorptive dysfunction (α1-microglobulin [a1m], β2-microglobulin, trefoil factor 3); tubular injury (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1]); kidney repair (epidermal growth factor); tubular reserve (uromodulin); and glomerular injury (urinary albumin). Incident CKD was defined as eGFR <60 ml/min/1.73 m 2 measured at two consecutive 6-month visits with an average annual eGFR decline ≥3% per year. During a median follow-up of 7 years, 11% developed CKD. Urinary albumin and KIM-1 mediated 32% (95% CI: 13.4%, 76.6%) and 23% (6.9%, 60.7%) of the association between SBP and incident CKD, respectively; and 19% (5.1%, 42.3%) and 22% (8.1%, 45.7%) of the association between DBP and incident CKD, respectively. Urinary albumin, α1m, and IL-18 were significant mediators of the association between Hba1c and incident CKD. None of the eight biomarkers mediated the association between serum albumin and incident CKD. Among women living with HIV, several urinary biomarkers reflecting distinct dimensions of kidney health may partially explain the associations between SBP, DBP, and Hba1c and subsequent CKD risk.