Women's Interagency HIV Study Research Articles

Machine Learning Estimation of Low-Density Lipoprotein Cholesterol in Women With and Without HIV.

Low-density lipoprotein cholesterol (LDL-C) is typically estimated from total cholesterol, high-density lipoprotein cholesterol, and triglycerides. The Friedewald, Martin-Hopkins, and National Institutes of Health equations are widely used but may estimate LDL-C inaccurately in certain patient populations, such as those with HIV. We sought to investigate the utility of machine learning for LDL-C estimation in a large cohort of women with and without HIV. We identified 7397 direct LDL-C measurements (5219 from HIV-infected individuals, 2127 from uninfected controls, and 51 from seroconvertors) from 2414 participants (age 39.4 ± 9.3 years) in the Women's Interagency HIV Study and estimated LDL-C using the Friedewald, Martin-Hopkins, and National Institutes of Health equations. We also optimized 5 machine learning methods [linear regression, random forest, gradient boosting, support vector machine (SVM), and neural network] using 80% of the data (training set). We compared the performance of each method using root mean square error, mean absolute error, and coefficient of determination (R2) in the holdout (20%) set. SVM outperformed all 3 existing equations and other machine learning methods, achieving the lowest root mean square error and mean absolute error, and the highest R2 (11.79 and 7.98 mg/dL, 0.87, respectively, compared with those obtained using the Friedewald equation: 12.45 and 9.14 mg/dL, 0.87). SVM performance remained superior in subgroups with and without HIV, with nonfasting measurements, in LDL <70 mg/dL and triglycerides > 400 mg/dL. In this proof-of-concept study, SVM is a robust method that predicts directly measured LDL-C more accurately than clinically used methods in women with and without HIV. Further studies should explore the utility in broader populations.

Integrase Inhibitors are Associated with Neuropsychiatric Symptoms in Women with HIV.

Women with HIV(WWH) are more likely to discontinue/change antiretroviral therapy(ART) due to side effects including neuropsychiatric symptoms. Efavirenz and integrase strand transfer inhibitors(INSTIs) are particularly concerning. We focused on these ART agents and neuropsychiatric symptoms in previously developed subgroups of WWH that differed on key sociodemographic factors as well as longitudinal behavioral and clinical profiles.WWH from the Women's Interagency HIV Study were included if they had ART data available, completed the Perceived Stress Scale-10 and PTSD Checklist-Civilian. Questionnaires were completed biannually beginning in 2008 through 2016. To examine ART-symptom associations, constrained continuation ratio model via penalized maximum likelihood were fit within 5 subgroups of WWH.Data from 1882 WWH contributed a total of 4598 observations. 353 women were previously defined as primarily having well-controlled HIV with vascular comorbidities, 463 with legacy effects(CD4 nadir < 250cells/mL), 274 aged ≤ 45 with hepatitis, 453 between 35-55years, and 339 with poorly-controlled HIV/substance users. INSTIs, but not efavirenz, were associated with symptoms among key subgroups of WWH. Among those with HIV legacy effects, dolutegravir and elvitegravir were associated with greater stress/anxiety and avoidance symptoms(P's < 0.01); dolutegravir was also associated with greater re-experiencing symptoms(P = 0.005). Elvitegravir related to greater re-experiencing and hyperarousal among women with well-controlled HIV with vascular comorbidities(P's < 0.022). Raltegravir was associated with less hyperarousal, but only among women aged ≤ 45years(P = 0.001).The adverse neuropsychiatric effects of INSTIs do not appear to be consistent across all WWH. Key characteristics (e.g., age, hepatitis positivity) may need consideration to fully weight the risk-benefit ratio of dolutegravir and elvitegravir in WWH.

Regional Differences in Risk of Recurrent Falls Among Older U.S. Women and Men with HIV in the HIV Infection, Aging, and Immune Function Long-Term Observational Study.

Geographic location was a strong predictor of falls among women with and without HIV in the Women's Interagency HIV Study. We examined regional variation in falls in a more geographically diverse cohort of older people with HIV (PWH) and explored whether physical activity, sex, or body-mass index modified these associations. PWH enrolled in the A5322 HAILO (HIV Infection, Aging, and Immune Function Long-Term Observational Study). Participants who reported falls in the 6 months before each semiannual visit and had ≥1 consecutive pair of fall assessments were included. We examined associations of geographic region [Northeast, Midwest, South, and West] with recurrent falls (≥2) over each 12-month period using repeated measures multinomial logistic regression models and assessed effect modification by adding an interaction term between geographic region and each potential effect modifier. A total of 788 men and 192 women with median age of 51 years at study entry contributed up to 240 weeks of data. U.S. regions included Northeast (22%), Midwest (29%), South (20%), and West (28%). In multivariable analyses, compared with the Western region, greater risk was seen among Midwestern (odds ratio [OR] = 2.35 [95% confidence interval (CI) = 1.29-4.28]) and Southern regions (OR = 2.09 [95% CI = 1.09-4.01]). Among those with higher physical activity, the Midwestern region had higher odds of recurrent falls than the Western region. Among obese individuals, the Southern region had higher odds of recurrent falls than the Western region. Sex did not modify the association between region and recurrent falls. Among older PWH, fall risk varied by geographic region. Associations between geographic region and recurrent falls appeared to be modified by physical activity and obesity. This may help identify subgroups of older PWH for targeted fall screening/interventions.

Mental Health Mediates the Association Between Gender-Based Violence and HIV Treatment Engagement in US Women.

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. 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. 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. 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.

Exploring the Anal Microbiome in HIV Positive and High-Risk HIV Negative Women.

This exploratory study sought to characterize the anal microbiome and explore associations among the anal microbiome, risk factors for anal cancer, and clinical factors. A pilot sample of 50 HIV infected and high-risk HIV negative women were recruited from the former Women's Interagency HIV Study. Microbiome characterization by 16S rRNA gene sequencing and datasets were analyzed using QIIME 2™. Composition of the anal microbiome and its associations with anal cancer risk factors and clinical factors were analyzed using linear decomposition model and permutational multivariate analysis of variance. Composition of the anal microbiome among HIV positive and high-risk negative women was dominated by Bacteroides, Prevotella, and Campylobacter. The overall taxonomic composition and microbial diversity of the anal microbiome did not significantly differ by HIV status. However, the abundance of Ruminococcus 1 belonging to the Rumincoccaceae family was associated with HIV status (q = .05). No anal cancer risk factors were associated with the anal microbiome composition. Clinical factors marginally associated with the anal microbiome composition included body mass index (BMI; p = .05) and hepatitis C virus (HCV; p = .05). Although HIV and risk factors for anal cancer were not associated with the composition of the anal microbiome in this pilot sample, other clinical factors such as BMI and HCV, may be worth further investigation in a larger study. Future research can build on these findings to explore the role of the microbiome and HIV comorbidities in women.

The Association Between HIV Status, Estradiol, and Sex Hormone Binding Globulin Among Premenopausal Women in the Women's Interagency HIV Study.

Background: Characterizing estradiol among women with HIV may have implications for breast cancer and cardiovascular disease risk but has not been adequately explored. We quantified differences in total (E2), free (FE2) estradiol, and sex hormone binding globulin (SHBG) by HIV and viral suppression status. Methods: Women from a substudy (2003-2006) within the Women's Interagency HIV Study (IRB approved at each participating site) were included if they reported: a period in the last six months, were not pregnant/breastfeeding, no oophorectomy, and no exogenous hormone use in the prior year. Serum was collected on days 2-4 of the menstrual cycle. We assessed differences in biomarkers at 25th, 50th, and 75th percentiles by HIV and viral suppression status using weighted quantile regression. Results: Among 643 women (68% with HIV) median age was 37 years. All E2 percentiles were significantly (p < 0.05) lower in women with suppressed viral load versus women without HIV (4-10 pg/mL). The 25th and 50th percentile of E2 were 4-5 pg/mL lower in women with unsuppressed viral load compared to women without HIV (p < 0.05). The 25th and 50th percentile of SHBG was significantly higher in women with unsuppressed viral load compared to women without HIV (10 and 12 nmol/L, respectively). There were no consistent differences in estradiol or SHBG by suppression status. Conclusions: There were no differences in FE2 but significantly lower E2 and higher SHBG among women with HIV versus without HIV. Further research is merited in a large contemporary sample to clarify the clinical implications of these findings.

Perceptions of Anal Cancer Risk Among HIV-Positive and High-Risk HIV-Negative Women.

Women living with HIV (WLWH) have a greater risk of anal cancer than women without HIV; however, there are limited studies that examine awareness of anal cancer risk among WLWH and "high-risk" HIV-negative women. This study examines risk factors for anal cancer, perceptions of risk for anal cancer, and perceptions of anal cancer screening among a cohort of WLWH and high-risk HIV-negative women. From the Atlanta, GA, and Bronx, NY, sites of the Women's Interagency HIV Study, 155 WLWH and HIV-negative women were enrolled and the Champion Health Belief Model Scale questionnaire measuring risk perceptions to anal cancer was administered to each participant. The WLWH perceived anal cancer to be less serious and perceived facing fewer barriers to anal cancer screening than HIV-negative women (both p = .01). Older women (≥50 years) felt that they had less barriers to anal cancer screening (p = .047). Moreover, women who had less than a high school education felt more susceptible to anal cancer (p = .001), as did women who reported a history of anal intercourse (p = .017). Despite being at an increased risk for anal cancer, perceptions of susceptibility to anal cancer and seriousness of anal cancer were low among WLWH. These findings highlight opportunities for provider and patient educational interventions to improve awareness of anal cancer risk among WLWH.

Differences in Muscle Quantity and Quality by HIV Serostatus and Sex.

People with HIV (PWH) experience greater declines in both muscle function and muscle mass with aging. Whether changes in muscle quality and quantity with aging differ between men and women with HIV and the implications on muscle function are not established. In coordinated substudies of the Multicenter AIDS Cohort Study and Women's Interagency HIV Study, participants completed physical function and falls assessments; total trunk/thigh density, inversely related to fatty infiltration, and area were quantified from computed tomography (CT) scans. Generalized linear models were used to explore variables affecting density/area, and associations between area/density and physical function and falls. CT scans were available on 387 men (198 PWH) and 184 women (118 PWH). HIV serostatus was associated with greater lateralis, paraspinal, and hamstring area, but lower psoas area and density. Older age and female sex were associated with smaller trunk muscle area and lower density. Both lower muscle area and muscle density were associated with several measures of impaired physical function. The odds of falling were lower with greater hamstring density, but not associated with other measurers of muscle area or density. In summary, older adults with HIV appear to have smaller and less dense (fattier) psoas, a key component in truncal stability and hip flexion that could have implications on physical function. The longitudinal associations of muscle area and density with physical function require careful investigation, with a particular focus on characteristics and interventions that can preserve muscle area, density, and function over time.

Study of Treatment and Reproductive Outcomes Among Reproductive-Age Women With HIV Infection in the Southern United States: Protocol for a Longitudinal Cohort Study.

BackgroundNearly a quarter of the 1.1 million individuals with HIV in the United States are women. Racial and ethnic minority women in the Southern United States are disproportionately impacted. Reproductive-age women with HIV are prone to poor HIV outcomes but remain underrepresented in HIV research. We will answer contemporary questions related to the health outcomes in this population by enrolling a prospective cohort of reproductive-age women with and without HIV in the Southern United States.ObjectiveThe Study of Treatment and Reproductive Outcomes (STAR) will enroll and retain 2000 reproductive-age women with and without HIV. The STAR will leverage the infrastructure of the US-based Multicenter AIDS Cohort Study (MACS)/Women’s Interagency HIV Study (WIHS) Combined Cohort Study, comprising the WIHS (a cohort of women with and at risk for HIV, which began in 1993), and the MACS (a cohort of gay and bisexual men with and at risk for HIV, which began in 1984). Although the advancing age of the participants enrolled in the MACS/WIHS Combined Cohort Study provides an opportunity to address the questions related to HIV and aging, the research questions pertinent to the reproductive years must also be addressed. The STAR will conduct high-priority scientific research in key areas with the overall aim of addressing the unique needs of reproductive-age women with HIV.MethodsThe STAR is a prospective, observational cohort study that will be conducted at 6 sites in the United States—Atlanta, Georgia; Birmingham, Alabama; Jackson, Mississippi; Chapel Hill, North Carolina; Miami, Florida; and Washington, District of Columbia. Visits will occur semiannually for 2 years, with additional visits for up to 5 years. At each visit, the participating women will complete a structured interview for collecting key demographic, psychosocial, and clinical variables, and undergo biospecimen collection for laboratory testing and repositing (blood, urine, hair, vaginal, anal, and oral specimens). Pregnant women and infants will undergo additional study assessments. The initial scientific focus of the STAR is to understand the roles of key social determinants of health, depression, reproductive health, and oral health on HIV and pregnancy outcomes across the reproductive life span.ResultsEnrollment in the STAR commenced in February 2021 and is ongoing.ConclusionsThrough in-depth, longitudinal data and biospecimen collection, the newly initiated STAR cohort will create a platform to answer scientific questions regarding reproductive-age women with and without HIV. STAR will be uniquely positioned to enable investigators to conduct high-impact research relevant to this population. Building on the legacy of the MACS and WIHS cohorts, the STAR is designed to foster multidisciplinary collaborations to galvanize scientific discoveries to improve the health of reproductive-age women with HIV and ameliorate the effects of the HIV epidemic in this population in the United States.

I Think I Age Gracefully: A Focus Group Study of Successful Aging Conceptions Among Older Women Living With HIV

Our previous quantitative research found high prevalence of self-rated successful aging (SA) among older (age ≥50) women living with HIV (OWLH) enrolled in the Women’s Interagency HIV Study (WIHS). However, little is known about how OWLH define SA. Most studies have examined SA among predominantly white men living with HIV. Therefore, the purpose of our qualitative study was to examine subjective understandings of SA among OWLH and, as a comparison group, older HIV-seronegative women at risk of HIV. Four focus group discussions (FGD) were conducted among 23 participants (12 OWLH, 11 HIV-seronegative). These women were recruited from WIHS participants previously enrolled in our quantitative study of SA, “From Surviving to Thriving” (FROST), at two WIHS sites – Atlanta and Brooklyn. At each site, we conducted two FGD – one with OWLH and one with older HIV-seronegative women in February-March of 2019. Participants were, on average, 56 years old (range, 51-70), 78% Black, and 60% with annual income ≤ $12,000. A team of coders conducted thematic coding of fully transcribed FGD using MAXQDA software. Several themes emerged. Both OWLH and older HIV-seronegative women defined SA as “aging gracefully,” i.e. accepting and celebrating aging after having survived hardships of earlier life (e.g., HIV diagnosis, drug use). They also emphasized taking care of themselves (e.g., taking their meds) and spirituality in their definitions of SA. In contrast to HIV-seronegative participants, who prioritized sobriety as taking good care of themselves, OWLH emphasized taking care of their HIV (e.g., “staying on top of your numbers”).

Overweight, Obesity, and Neuropsychological Performance: Results From the Women’s Interagency HIV Study

Conflicting associations of body mass index (BMI) and waist circumference (WC) with neuropsychological performance (NP) are observed in the general population and among people living with HIV. We examined BMI and WC in middle-aged women living with HIV (WLWH) and without HIV (HIV-) in relation to 10-year trajectories of NP in the Women’s Interagency HIV Study (WIHS). NP assessments occurred biennially from 2009-2019. Demographically-adjusted T-scores were calculated for six NP domains: learning, memory, executive function, processing speed, attention and working memory, and motor function. Multivariable linear models stratified by HIV serostatus examined whether baseline (2009) BMI and WC were associated with NP domains - 1) cross-sectionally and 2) longitudinally over 10 years. The sample included 432 WLWH and 367 HIV- women, >40 years old. Most women (73%) were overweight (BMI=25-29.9kg/m2) or obese (BMI=>30kg/m2). Among WLWH, 28% were overweight, 45% obese; among HIV- women, 26% were overweight; 56% obese. Cross-sectionally at baseline, WLWH who were overweight versus normal weight (BMI=18.5-24.9kg/m2), performed worse on executive function, processing speed, and motor function (all p<0.05). HIV- women who were overweight versus normal weight performed worse on memory, learning, executive function, processing speed and motor function (all p<0.05). Baseline BMI and WC were not associated with worsening NP domains in this younger, primarily overweight and obese sample of WLWH or HIV- women (all p>0.05).Future follow-up of these women will enhance understanding of the age when total and/or central obesity may influence NP trajectories and health of the aging brain.

High Provider Trust Associates with High HIV Antiretroviral Adherence Among Women Living with HIV in a Metropolitan Washington, DC Cohort.

Trust in providers and health care systems (HCSs) has been associated with higher HIV antiretroviral (ART) adherence; however, most previous studies enrolled primarily men and did not concurrently assess provider trust, HCS distrust, and clinical/biological outcomes. We enrolled 239 Washington, DC Women's Interagency HIV Study (WIHS) women: 167 with HIV (WWH) and 72 without HIV. In 2006 and 2017-2018, women completed surveys on provider trust and HCS distrust. Clinical, social, and demographic covariates were obtained during the 2017-2018 WIHS study visit. Descriptive analyses included chi-squared and Mann-Whitney tests. Wilcoxon signed-rank tests assessed trust measure change over time. Logistic (provider trust) and linear (HCS distrust) models were constructed in R. The majority of women were African American/Black (76.9%) with a median age of 52 (interquartile range 48, 58) and currently insured (99.6%). In multi-variable analyses, women with HIV (WWH) had higher odds of high provider trust [adjusted odds ratio (aOR) 2.90, 95% confidence interval (CI) 1.34, 6.45], with ≥95% ART adherence associated with high provider trust among only WWH (aOR 4.13, 95% CI 1.14, 15.92). Multi-variable models also showed 3.40-point higher HCS distrust scores among WWH who reported ≥95% ART adherence (p = 0.03). CD4 count and HIV viral load were not associated with provider trust or HCS distrust. Provider (p = 0.67) and HCS (p = 0.65) trust did not significantly change in this population at two time points for 10 years. Self-reported antiretroviral therapy adherence significantly associated with high provider trust, yet also with high HCS distrust, revealing a nuanced relationship to providers and the HCS among WWH.

Molecular profiling of breast and lung cancer in women with HIV reveals high tumor mutational burden.

This study compared the mutation profile and tumor mutational burden (TMB) in women with HIV (WWH) diagnosed with lung adenocarcinoma (n = 8) or breast ductal neoplasm (n = 13) who were enrolled into the Women's Interagency HIV Study (WIHS). Previous studies tended to focus on single institutions based on sample availability. This study is based on a representative, multicenter cohort that represents the racial and ethnic composition of women with HIV in the United States. The study sequenced the complete human exome of n = 26 cancer samples from HIV-positive women, using Ion torrent next-generation sequencing. The study cohort was compared with a HIV-negative cohort obtained from the Genomic Data Commons Data Portal of the NCI. There were no differences in known cancer mutations between breast cancer and lung cancer that developed in WWH and those that developed in HIV-negative (HIV-) women; however, WWH presented a significantly higher TMB in comparison to HIV- patients. Seventy-five percent of lung cancers and 61% of breast cancers were defined as TMB-high (more than 10 mutation/mb of DNA). This study affirms the recommendation that WWH be included in clinical trials of novel treatments for these cancers. Although these data are preliminary, the high TMB in WLHV suggests, paradoxically, that this immune challenged population may benefit greatly from immune checkpoint inhibitor therapies.

Association of Poor Sleep With Depressive and Anxiety Symptoms by HIV Disease Status: Women's Interagency HIV Study.

Background:Sleep disturbances are prevalent in women living with HIV (WLWH) and can affect mental health and overall quality of life. We examined the prevalence and predictors of poor sleep quality in a US cohort of WLWH and HIV-uninfected controls and the relationship between sleep quality and mental health symptom burden stratified by HIV disease status (viremic WLWH, aviremic WLWH, and HIV-uninfected women).Methods:Sleep quality was assessed using the Pittsburgh Sleep Quality Index in 1583 (400 viremic WLWH, 723 aviremic WLWH, and 460 HIV-uninfected women) Women's Interagency HIV Study participants. Depressive and anxiety symptoms were concurrently assessed using the Center for Epidemiological Studies-Depression (CES-D) scale and General Anxiety Disorder (GAD-7) scale. Associations between poor sleep quality (global Pittsburgh Sleep Quality Index >5) and both high depressive (CES-D ≥16) and anxiety (GAD-7 ≥10) symptoms were each assessed by HIV disease status using multivariable logistic regression models.Results:Prevalence of poor sleep quality in the overall sample was 52%, differed by HIV disease status (P = 0.045), and was significantly associated with high depressive and anxiety symptoms in (1) viremic WLWH, (2) aviremic WLWH, and (3) HIV-uninfected women [CES-D: (1) adjusted odds ratio (aOR) = 7.50, 95% confidence interval (CI): 4.10 to 13.7; (2) aOR = 4.54, 95% CI: 3.07 to 6.73; and (3) aOR = 6.03, 95% CI: 3.50 to 10.4; GAD-7: (1) aOR = 5.20; 95% CI: 2.60 to 10.4, (2) aOR = 6.03; 95% CI: 3.67 to 9.91, and (3) aOR = 6.24; 95% CI: 3.11 to 12.6].Conclusions:Poor sleep quality is highly prevalent, as is mental health symptom burden, among WLWH and HIV-uninfected controls. Future longitudinal studies are necessary to clarify the directionality of the relationship.

Examining the Relationships Between Experienced and Anticipated Stigma in Health Care Settings, Patient-Provider Race Concordance, and Trust in Providers Among Women Living with HIV.

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.

Positive Psychological Factors and Life Themes in Relation to Health Outcomes in Women Living with HIV.

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). 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 6months later. Composite scores across the two time points were used in all analyses. 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. Findings that positive psychological factors and life accomplishments may relate to better health, especially tolower depression, potentially contribute to developing positive psychology interventions for Black WLWH.

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

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. 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. 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. 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.

Cardiovascular risk score associations with frailty in men and women with or at risk for HIV.

To understand the relationship between cardiovascular disease (CVD) risk and frailty among men (MWH) and women living with HIV (WWH), or at risk for HIV. We considered 10-year coronary heart disease and atherosclerotic CVD risk by Framingham risk score (FRS, 2001 National Cholesterol Education Program Adult Treatment Program III) and Pooled Cohort Equations (PCE, 2013 American College of Cardiology/American Heart Association) in relation to the Fried Frailty Phenotype (FFP) in the Multicenter AIDS Cohort Study (MACS) and Women's Interagency HIV Study (WIHS). FFP was ascertained in MACS from 2004 to 2019 and in WIHS from 2005 to 2006 and 2011-2019. FFP score at least three of five components defined frailty. Repeated measures logistic regression (both cohorts) and Cox proportional hazards regression (MACS) were performed, controlled for education, income, cholesterol medication and hepatitis C virus serostatus, and among MWH and WWH, CD4+ cell count/μl, antiretroviral therapy, and HIV viral load. There were 5554 participants (1265 HIV seronegative/1396 MWH; 768 seronegative/1924 WWH) included. Among men, high-risk FRS was associated with increased risk of incident frailty among seronegative [adjusted hazard ratio (aHR)) = 2.12, 95% confidence interval (CI):1.22-3.69] and MWH (aHR = 2.19, 95% CI: 1.33-3.61). Similar associations were seen with high-risk PCE and incident frailty among SN (aHR = 1.88, 95% CI: 1.48-2.39) and MWH (aHR = 1.59, 95% CI: 1.26-2.00). Among women, high-risk PCE was associated with frailty in SN [adjusted odds ratio (aOR) = 1.43, 95% CI: 1.02-2.00] and WWH (aOR = 1.36, 95% CI: 1.08-1.71); however, high-risk FRS was not (seronegative: aOR = 1.03, 95% CI: 0.30-3.49; WWH: aOR = 0.86, 95% CI: 0.23-3.20). Higher CVD risk was associated with increased frailty regardless of HIV serostatus among men and women. These findings may inform clinical practices of screening for frailty.

Long-Acting Injectable ART and PrEP Among Women in Six Cities Across the United States: A Qualitative Analysis of Who Would Benefit the Most.

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.

Patient Health Literacy and Communication with Providers Among Women Living with HIV: A Mixed Methods Study.

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.