Cognitive changes during the menopausal transition: a longitudinal study in women with and without HIV

OBJECTIVE: To assess longitudinal changes in cognitive performance across menopause stages in a sample comprised primarily of low-income women of color, including women with HIV (WWH). METHODS: A total of 443 women (291 WWH; 69% African American; 18% Hispanic; median age = 42 y) from the Women's Interagency HIV Study completed tests of verbal learning and memory, attention/working memory, processing speed, verbal fluency, motor skills, and executive function first at an index premenopausal visit and thereafter once every 2 years for up to six visits (mean follow-up = 5.7 y). General linear-mixed effects regression models were run to estimate associations between menopause stages and cognition, in the overall sample and in WWH. We examined both continuous scores and categorical scores of cognitive impairment (yes/no >1 standard deviation below the mean). RESULTS: Adjusting for age and relevant covariates, the overall sample and WWH showed longitudinal declines in continuous measures of learning, memory, and attention/working memory domains from the premenopause to the early perimenopause and from the premenopause to the postmenopause, Ps < 0.05 to < 0.001. Effects on those same domains were also evident in categorical scores of cognitive impairment, with the increased odds of impairment ranging from 41% to 215%, Ps < 0.05 to < 0.001. The increase in predicted probability of impairment by menopausal stage (% affected) ranged from 4% to 13%. CONCLUSIONS: Menopause stage was a key determinant of cognition in a sample of low-income women of color, including WWH. Many of these changes reached a clinically significant level of cognitive impairment

Intensity of Social Support Matters: A Latent Class Analysis to Identify Levels of Social Support Associated with Optimal Health Outcomes Among Women Living with HIV

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

Class-Based Antiretroviral Exposure and Cognition Among Women Living with HIV

Neurologic complications of the human immunodeficiency virus (HIV) are common in treated individuals, and toxicity of certain antiretroviral therapies (ART) may contribute to cognitive impairment. We investigated exposures to specific ART and cognition among women living with HIV (WLWH). Virologically suppressed (viral load <200 copies/mL during at least two semi-annual visits) WLWH and age/race matched HIV-seronegative controls enrolled in the Women's Interagency HIV Study who completed at least two biennial cognitive assessments were included. Analysis of WLWH was restricted to those with exposure to the drug class of interest and a nucleoside reverse transcriptase inhibitor (NRTI) backbone. Generalized estimating equations were used to evaluate repeated measures of cognition over time in association with ART class exposure. Among 1,242 eligible WLWH, 20% (n = 247) had isolated drug exposure to non-nucleoside reverse transcriptase inhibitors (NNRTI), 18% (n = 219) to protease inhibitors (PIs), and 6% (n = 79) to integrase inhibitors with a NRTI backbone. Cognitive assessments were performed at a median of 3 biennial visits {IQR 2-4 visits}. At the index assessment, 21% of WLWH demonstrated global cognitive impairment versus 29% at their last cognitive assessment. In multivariable analyses adjusted for hypertension, depression, diabetes mellitus, history of AIDS-defining illness, alcohol use, number of medications, and time on ART, WLWH exposed to NNRTIs demonstrated verbal learning improvements (mean T-score change 1.3, p = .020) compared to other treated women. Compared to HIV-seronegative women, WLWH exposed to PIs had worse verbal learning (mean T-score difference -2.62, p = .002) and verbal memory performance (mean T-score difference -1.74, p = .032) at baseline. Compared to HIV-seronegative women, WLWH exposed to PIs had improvements in verbal learning (mean T-score slope difference 0.36, p = .025) and verbal memory (mean T-score slope difference 0.32, p = .042). The index T-score and slope of change in the T-score were similar among other treated groups and the HIV-seronegative group. We noted emerging trends in cognition in WLWH exposed to specific drug classes. Ongoing study of this relatively young group is important to characterize long-term cognitive outcomes and effect of antiretrovirals as treatment guidelines evolve

Human Immunodeficiency Virus and Cardiac End-Organ Damage in Women: Findings From an Echocardiographic Study Across the United States

BACKGROUND: People with human immunodeficiency virus (HIV) have been reported to have increased risk of clinical and subclinical cardiovascular disease. Existing studies have focused on men and often have been uncontrolled or lacked adequate HIV-negative comparators. METHODS: We performed echocardiography in the Women's Interagency HIV Study to investigate associations of HIV and HIV-specific factors with cardiac phenotypes, including left ventricular systolic dysfunction (LVSD), isolated LV diastolic dysfunction (LVDD), left atrial enlargement (LAE), LV hypertrophy (LVH), and increased tricuspid regurgitation velocity (TRV). RESULTS: Of 1654 participants (age 51 ± 9 years), 70% had HIV. Sixty-three (5.4%) women with HIV (WWH) had LVSD; 71 (6.5%) had isolated LVDD. Compared with women without HIV (WWOH), WWH had a near-significantly increased risk of LVSD (adjusted relative risk = 1.69; 95% confidence interval = 1.00 to 2.86; P = .051). No significant association was noted for HIV seropositivity with other phenotypes, but there was a risk gradient for decreasing CD4+ count among WWH that approached or reached significance for isolated LVDD, LAE, and LVH. WWH with CD4+ count <200 cells/mm3 had significantly higher prevalence of LAE, LVH, and high TRV than WWOH. There were no consistent associations for viral suppression or antiretroviral drug exposure. CONCLUSIONS: This study suggests that WWH have a higher risk of LVSD compared with sociodemographically similar WWOH, but their risk for isolated LVDD, LAE, LVH, and high TRV is increased only with reduced CD4+ count. Although these findings warrant replication, they support the importance of cardiovascular risk-factor and HIV-disease control for heart disease prevention in this population

Cohort profile: The women’s interagency HIV study (WIHS)

Why was the cohort set up? The National Institutes of Health established the Women’s Interagency HIV Study (WIHS) in 1993 to study the impact and progression of HIV infection among women in response to the rising number of AIDS cases and the relative paucity of clinical, behavioural and epidemiological data in this population. Women now comprise more than 50% of people with HIV (PWH) worldwide.1 The WIHS is the largest and oldest ongoing prospective cohort study of women with and at risk for HIV infection in the world, and remains the leading study to document the experience of women with HIV (WWH) in the United States

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

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

The Relationship Between Discrimination and Missed HIV Care Appointments Among Women Living with HIV

Receiving regular HIV care is crucial for maintaining good health among persons with HIV. However, racial and gender disparities in HIV care receipt exist. Discrimination and its impact may vary by race/ethnicity and gender, contributing to disparities. Data from 1578 women in the Women’s Interagency HIV Study ascertained from 10/1/2012 to 9/30/2016 were used to: (1) estimate the relationship between discrimination and missing any scheduled HIV care appointments and (2) assess whether this relationship is effect measure modified by race/ethnicity. Self-reported measures captured discrimination and the primary outcome of missing any HIV care appointments in the last 6 months. Log-binomial models accounting for measured sources of confounding and selection bias were fit. For the primary outcome analyses, women experiencing discrimination typically had a higher prevalence of missing an HIV care appointment. Moreover, there was no statistically significant evidence for effect measure modification by race/ethnicity. Interventions to minimize discrimination or its impact may improve HIV care engagement among women

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

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

Mechanisms linking gender-based violence to worse HIV treatment and care outcomes among women in the United States

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

Examining adherence barriers among women with HIV to tailor outreach for long-acting injectable antiretroviral therapy

Background: Long-acting (LA) injectable antiretroviral therapy (ART) has been found non-inferior to daily oral ART in Phase 3 trials. LA ART may address key barriers to oral ART adherence and be preferable to daily pills for some people living with HIV. To date, women have been less represented than men in LA ART research. Using longitudinal data from the Women's Interagency HIV Study (WIHS) cohort of women living with HIV in the United States, we examined barriers and facilitators of daily oral ART adherence that may be related to or addressed by LA ART. Methods: We conducted a secondary analysis of WIHS cohort data from 1998 to 2017 among participants seen for at least 4 visits since 1998 who reported using ART at least once (n = 2601). Two dichotomous outcomes, patient-reported daily oral ART adherence and viral suppression were fit using generalized linear models, examining the role of socio-demographic and structural factors. Results: At study enrollment, the median age was 40.5 years, 63% of participants were African American and 22% were Latina. The majority (82%) reported taking ART more than 75% of the time and 53% were virally suppressed. In multivariate analysis, several sub-groups of women had lower odds of reported adherence and viral suppression: 1) younger women (adherence aOR: 0.71; viral suppression aOR: 0.63); 2) women who inject drugs (adherence aOR: 0.38; viral suppression aOR: 0.50) and those with moderate (adherence aOR: 0.59; viral suppression aOR: 0.74) and heavy alcohol consumption (adherence aOR: 0.51; viral suppression aOR: 0.69); 3) those with depressive symptoms (adherence aOR: 0.61; viral suppression aOR: 0.76); and 4) those with a history of going on and off ART (adherence aOR: 0.62, viral suppression aOR: 0.38) or changing regimens (adherence aOR: 0.83, viral suppression aOR: 0.56). Conclusions: Current injectable contraceptive users (vs. non-users) had greater odds of oral ART adherence (aOR: 1.87) and viral suppression (aOR: 1.28). Findings identify profiles of women who may benefit from and be interested in LA ART. Further research is warranted focused on the uptake and utility of LA ART for such key subpopulations of women at high need for innovative approaches to achieve sustained viral suppression