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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.)

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.)

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: 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.)

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.)

Background: Adherence to antiretroviral therapy (ART) is imperative for viral suppression and reducing HIV transmission, but many people living with HIV report difficultly sustaining long-term adherence. Long-acting injectable (LAI) ART has the potential to transform HIV treatment and prevention. However, little LAI ART-related behavioral research has occurred among women, particularly outside of clinical trials., Setting: Six Women's Interagency HIV Study sites: New York, Chicago, Washington DC, Atlanta, Chapel Hill, and San Francisco., Methods: We conducted 59 in-depth interviews with women living with HIV across 6 Women's Interagency HIV Study sites (10 per site; 9 at Washington DC). We interviewed women who were not included in LAI ART clinical trials but who receive care at university settings that will administer LAI ART once it is approved. Interviews were recorded, transcribed, and analyzed using thematic content analysis., Results: Most women enthusiastically endorsed monthly LAI ART and would prefer it over pills. The following 3 reasons emerged for this preference: (1) convenience and confidentiality, (2) avoiding daily reminders about living with HIV, and (3) believing that shots are more effective than pills. Challenges remain, however, specifically around (1) medical mistrust, (2) concerns about safety and effectiveness, (3) pill burden for HIV and other conditions, and (4) barriers to additional medical visits., Conclusions: Most women preferred LAI ART over daily pills given its benefits, including convenience, privacy, and perceived effectiveness. Future research should incorporate more women into LAI ART trials to better understand and align development with user concerns and preferences to enhance uptake.

Background: Persistent inflammation is a life-long complication of HIV infection, even in virally suppressed individuals. Elevated plasma concentrations of soluble(s) CD14 and CD163 have been established as biomarkers of chronic inflammation, conferring higher risk for cognitive, neurovascular, and structural abnormalities., Methods: Structural magnetic resonance imaging (frontal and temporal regions) as well as plasma inflammatory biomarkers of monocyte activation (sCD14 and sCD163), general inflammation (plasma C-reactive protein, interleukin[IL]-6), and gut microbial translocation (plasma intestinal fatty acid-binding protein) were available on 38 women (25 with HIV) from the Chicago Women's Interagency HIV Study site. Partial least-squares models adjusting for relevant covariates (eg, age, education, and race) were conducted to evaluate the relationship between inflammatory biomarkers and brain volume in the overall sample and among women with HIV (WWH)., Results: In the total sample, higher plasma sCD14 was associated with smaller volumes in multiple frontal and temporal lobe regions. In the WWH-only sample, sCD163 was associated with smaller volumes only in one region of the left frontal lobe. C-reactive protein, IL-6, and intestinal fatty acid-binding protein were not associated with brain volumes for either group of women., Conclusions: Of the inflammatory monocyte markers evaluated, sCD14 was associated with smaller frontal and temporal cortical volume in the overall and WWH-only samples, while plasma sCD163 was only associated with smaller left caudal middle frontal gyrus in the WWH-only group. Validating these monocyte proteins as neurological biomarkers of structural brain deficits in a larger sample is critical for understanding HIV-associated neurobiological complications.

Background: Sub-Saharan African adolescents living with HIV face challenges to antiretroviral therapy (ART) adherence. Poor mental health drives nonadherence but can be improved with cognitive behavioral therapy (CBT). CBT delivered by peers may strengthen effects while building capacity for sustainment in low-income countries. This case study retrospectively applied the Exploration Preparation Implementation Sustainment framework to characterize the execution of the Kigali Imbereheza Project, a 2-arm individually randomized group controlled trial of Trauma-Informed Adherence-Enhanced CBT (TI-CBTe) delivered by Rwandan youth leaders (YLs) to adolescents living with HIV., Methods: YL (n = 14, 43% female, M = 22.71 years) had confirmed HIV and self-reported ART adherence >95%. Participants (n = 356, 51% female, M = 16.78 years) living with HIV were randomized to TI-CBTe or usual care. Two YLs co-led TI-CBTe sessions over 2 months for a total of 12 hours, while other YL observed and rated fidelity. Participants reported on YL competence. Additional data evaluated feasibility, acceptability, uptake, and fidelity., Results: In the Exploration phase, focus groups, stakeholder meetings, and individual interviews revealed strong consensus for delivering TI-CBT to reduce adolescent depression and trauma and improve ART adherence. In the Preparation phase, curriculum revisions were made, YLs were successfully trained, and a cascading supervision model was established. In the Implementation phase, YL delivered TI-CBTe with close monitoring and supervision. Findings revealed strong feasibility, acceptability, uptake, and fidelity, increasing the likelihood of Sustainment., Conclusions: Exploration Preparation Implementation Sustainment can guide implementation planning and delivery and evaluate implementation outcomes.

Background: Data are limited on cumulative impacts of depression on engagement in care and HIV outcomes in women living with HIV (WLWH) during the era of universal antiretroviral therapy (ART). Understanding the relationship of accumulated depression with HIV disease management may help identify benefits of interventions to reduce severity and duration of depressive episodes., Setting: A cohort of WLWH (N = 1491) from the Women's Interagency HIV Study at 9 sites across the US., Methods: This longitudinal observational cohort study (2013-2017) followed WLWH for a maximum of 9 semiannual visits. Depression was quantified as a time-updated measure of percent of days depressed (PDD) created from repeated assessments using the Center for Epidemiologic Studies Depression scale. Marginal structural Poisson regression models were used to estimate the effects of PDD on the risks of missing an HIV care appointment, <95% ART adherence, and virological failure (≥200 copies/mL)., Results: The risk of missing an HIV care appointment [risk ratio (RR) = 1.16, 95% confidence interval = 0.93 to 1.45; risk difference (RD) = 0.01, -0.01 to 0.03], being <95% ART adherent (RR = 1.27, 1.06-1.52; RD = 0.04, -0.01 to 0.07), and virological failure (RR = 1.09, 1.01-1.18; RD = 0.01, -0.01 to 0.03) increased monotonically with increasing PDD (comparing those with 25 to those with 0 PDD). The total effect of PDD on virological failure was fully (%100) mediated by being <95% ART adherent., Conclusions: Time spent depressed increases the risk of virological failure through ART adherence, even in the era of universal ART regimes forgiving of imperfect adherence.

Background: Expression of tissue factor (TF) on the surface of activated monocytes may trigger thrombosis, leading to clotting risk, inflammation, and atherosclerosis. TF-positive microparticles (MP-TF) represent a functionally active form of TF that may be promulgated by long-term HIV infection. We hypothesized that greater MP-TF activity is associated with carotid artery plaque in HIV+ women., Setting: In a case-control study nested within the Women's Interagency HIV Study (WIHS), eligible HIV+ participants underwent B-mode carotid artery ultrasound at 2 study visits occurring 7 years apart. Cases were defined by the presence of at least 1 carotid artery plaque assessed at either visit. Cases were matched 1:2 to controls who were found not to have carotid artery plaques., Methods: Conditional logistic regression estimated the association of MP-TF activity with the presence of carotid artery plaque, adjusting for demographic and behavioral characteristics, HIV-related factors, cardiometabolic risk factors, and serum inflammation biomarkers (high-sensitivity C-reactive protein, IL-6, sCD14, sCD163, Gal-3, and Gal-3BP)., Results: Elevated MP-TF activity (>0.537 pg/mL) was found to be significantly associated with greater odds of plaque (adjusted odds ratio 3.86, 95% confidence interval: 1.06 to 14.07, P = 0.04). The association was attenuated after further adjustment for IL-6 but was unaffected by adjustment for other biomarkers including those denoting monocyte activation., Conclusions: Our findings suggest a link among HIV infection, innate immune system perturbation, coagulation, and atherosclerosis.

Objectives: We compared skeletal microarchitecture using trabecular bone score (TBS) and evaluated relationships between change in TBS and lumbar spine (LS) bone mineral density (BMD) in women with and without HIV., Methods: Dual-energy X-ray absorptiometry was performed on 319 women with HIV and 118 without HIV in the Women's Interagency HIV Study at baseline and 2 and 5 years, to measure regional BMD and lean and fat mass. TBS was extracted from LS dual-energy X-ray absorptiometry images and examined continuously and categorically [normal (≥1.35), intermediate (1.20-1.35), or degraded (≤1.20) microarchitecture]. Pearson correlation and linear regression examined associations of TBS with regional BMD at baseline and over time., Results: Women with HIV were older (43 vs. 37 years), more likely to be postmenopausal (27% vs. 4%), have lower baseline total fat mass, trunk fat, and leg fat than uninfected women, degraded microarchitecture (27% vs. 9%, P = 0.001), and lower baseline mean TBS (1.3 ± 0.1 vs. 1.4 ± 0.1, P < 0.001). After adjusting for age, race, menopause status, and body mass index, TBS remained lower in women with HIV (P < 0.0001). Annual change in TBS correlated with LS BMD change among women with HIV (r = 0.36, P < 0.0001) and without HIV (r = 0.26, P = 0.02); however, mean % annual TBS change did not differ by HIV status (-1.0%/yr ± 2.9% for HIV+ vs. -0.8%/yr ± 1.7% for HIV-, P = 0.42)., Conclusions: Women with HIV have worse bone microarchitecture than uninfected women, but annual percent change in LS BMD or TBS was similar. Use of TBS as an adjunct to BMD to improve prediction of fragility fractures in women with HIV merits further study.

Background: A low proportion of CD28CD8 T cells that express CD57 is associated with increased mortality in HIV infection. The effect of increasing body mass index (BMI) changes in the proportion of CD57CD28CD8 T cells among HIV-infected individuals on antiretroviral therapy is unknown., Setting: In a US cohort of HIV-infected women, we evaluated associations of BMI and waist circumference with 3 distinct CD8 T cell phenotypes: % CD28CD57CD8 T cells, % CD57 of CD28CD8 T cells, and % CD28 of all CD8 T cells., Methods: Multivariable linear regression analysis was used to estimate beta coefficients for each of 3 T-cell phenotypes. Covariates included HIV parameters (current and nadir CD4, current viral load), demographics (age, race, income, and study site), and lifestyle (tobacco and alcohol use) factors., Results: Of 225 participants, the median age was 46 years and 50% were obese (BMI >30 m/kg). Greater BMI and waist circumference were both associated with higher % CD28CD57CD8 T cells and % CD57 of all CD28CD8 T cells in multivariable analysis, including adjustment for HIV viral load (all P < 0.05). The association between greater BMI and the overall proportion of CD28 CD8 cells in fully adjusted models (0.078, 95% confidence interval: -0.053 to 0.209) was not significant., Conclusions: In this analysis, greater BMI and waist circumference are associated with greater expression of CD57 on CD28CD8 T cells and a greater proportion of CD57CD28 CD8 T cells. These findings may indicate that increasing BMI is immunologically protective in HIV-infected women. Future research is needed to understand the prognostic importance of these associations on clinical outcomes.

Objectives: We evaluated the Veterans Aging Cohort Study (VACS) Index score, an index composed of age, CD4 count, viral load, hemoglobin, Hepatitis C coinfection, Fibrosis Index-4, and estimated glomerular filtration rate, and psychosocial and clinical risk factors for all-cause hospitalization among HIV-infected women on highly active antiretroviral therapy and HIV-uninfected women., Methods: Data were collected from 2008 to 2014 from 1585 highly active antiretroviral therapy-experienced HIV infected and 692 uninfected women. Cox proportional hazards regression evaluated predictors of first hospitalization over 2 years., Results: Among HIV-infected women, VACS Index score (per 5 points) [adjusted hazard ratio (aHR) 1.08; 95% confidence interval (CI): 1.06 to 1.11], Centers for Epidemiologic Studies-Depression (CESD) scores ≥16 (aHR 1.61; 95% CI: 1.30 to 1.99), smoking (aHR 1.26; 95% CI: 1.02 to 1.55), abuse history (aHR 1.52; 95% CI: 1.20 to 1.93), diabetes (aHR 1.63; 95% CI: 1.31 to 2.04), and black race (aHR 1.28; 95% CI: 1.03 to 1.59) increased risk of hospitalization. Among HIV-uninfected women, VACS Index score (aHR 1.08; 95% CI: 1.03 to 1.13), CESD scores ≥16 (aHR 1.38; 95% CI: 1.02 to 1.86), diabetes (aHR 2.15; 95% CI: 1.57 to 2.95), and black race (aHR 1.61; 95% CI: 1.15 to 2.24) predicted subsequent hospitalization., Conclusions: Psychosocial and clinical factors were associated with risk of hospitalization independently of the VACS Index score. Additional research on contextual and psychosocial influences on health outcomes among women is needed.

Background: Urine biomarkers have helped identify persons at risk for progressing to kidney disease in the setting of HIV infection. We explored factors associated with changes in 3 urine biomarkers over 10 years among women living with HIV., Methods: Prospective cohort of 294 HIV-infected women from the multicenter Women's Interagency HIV Study. Predictors included HIV viral and immunological parameters, comorbid conditions, and health-related behaviors. Outcomes were patterns of changes of urine interleukin-18 (IL-18), albumin-to-creatinine ratio (ACR), and alpha-1-microglobulin (α1m) over 10 years. We used quantile regression to examine patterns of change in each urine biomarker during follow-up and multivariable analysis of variance regression to identify predictors of biomarker changes., Results: Over 10 years, the median concentrations of IL-18 declined from 120 to 64 pg/mL, α1m rose from 0.7 to 1.5 ng/mL, and ACR remained stable (9-8 mg/g). In multivariate analyses, the strongest predictors of increases in IL-18 were higher baseline body mass index, increase in waist circumference, higher follow-up HIV viral load, lower follow-up CD4 cell count, hepatitis C virus (HCV) coinfection, and higher follow-up high density lipoprotein cholesterol. Predictors of increasing concentration of α1m were lower CD4 cell counts, higher diastolic blood pressure, HCV coinfection, and smoking. Finally, determinants of ACR increases during follow-up were higher follow-up diastolic blood pressure, HCV coinfection, higher follow-up HIV viral load, and triglyceride concentration., Conclusions: Over 10 years, HIV disease status had different associations with each urine biomarker under study. Overall, the associations with changes in each biomarker support research into their use for longitudinal monitoring of kidney health.

Objective: Because HIV impairs gut barriers to pathogens, HIV-infected adults may be vulnerable to minimal hepatic encephalopathy in the absence of cirrhosis., Background: Cognitive disorders persist in up to one-half of people living with HIV despite access to combination antiretroviral therapy. Minimal hepatic encephalopathy occurs in cirrhotic patients with or without HIV infection and may be associated with inflammation., Design/methods: A cross-sectional investigation of liver fibrosis severity using the aspartate aminotransferase to platelet ratio index (APRI) and neuropsychological testing performance among women from the Women's Interagency HIV Study. A subset underwent liver transient elastography (FibroScan, n = 303)., Results: We evaluated 1479 women [mean (SD) age of 46 (9.3) years]: 770 (52%) only HIV infected, 73 (5%) only hepatitis C virus (HCV) infected, 235 (16%) HIV/HCV coinfected, and 401 (27%) uninfected. Of these, 1221 (83%) exhibited APRI ≤0.5 (no or only mild fibrosis), 206 (14%) exhibited APRI >0.5 and ≤1.5 (moderate fibrosis), and 52 (3%) exhibited APRI >1.5 (severe fibrosis). Having moderate or severe fibrosis (APRI >0.5) was associated with worse performance in learning, executive function, memory, psychomotor speed, fluency, and fine motor skills. In these models that adjusted for fibrosis, smaller associations were found for HIV (learning and memory) and HCV (executive functioning and attention). The severity of fibrosis, measured by FibroScan, was associated with worse performance in attention, executive functioning, and fluency., Conclusions: Liver fibrosis had a contribution to cognitive performance independent of HCV and HIV; however, the pattern of neuropsychological deficit associated with fibrosis was not typical of minimal hepatic encephalopathy.

Background: Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence., Methods: The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced., Results: The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence., Conclusions: Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.

Background: Adding gender-related modifiable characteristics or behaviors to the Veterans Aging Cohort Study (VACS) index might improve the accuracy of predicting mortality among HIV-infected women on treatment. We evaluated the VACS index in women with HIV, determined whether additional variables would improve mortality prediction, and quantified the potential for improved survival associated with reduction in these additional risk factors., Methods: The VACS index (based on age, CD4 count, HIV-1 RNA, hemoglobin, aspartate aminotransferase, alanine aminotransferase, platelets, creatinine, and Hepatitis C status) was validated in HIV-infected women in the Women's Interagency HIV Study (WIHS) who initiated antiretroviral therapy between January 1996 and December 2007. Models were constructed adding race, depression, abuse, smoking, substance use, transactional sex, and comorbidities to determine whether predictability improved. Population attributable fractions were calculated., Results: The VACS index accurately predicted 5-year mortality in 1057 WIHS women with 1 year on highly active antiretroviral therapy with c-index 0.83 [95% confidence interval (CI): 0.79 to 0.87]. In multivariate analysis, the VACS index score [adjusted hazard ratio (aHR) for a 5-point increment 1.30; 95% CI: 1.25 to 1.35], depressive symptoms (aHR 1.73; 95% CI: 1.17 to 2.56), and history of transactional sex (aHR 1.93; 95% CI: 1.33 to 1.82) were independent statistically significant predictors of mortality., Conclusions: Both depression and transactional sex significantly improved the performance of the VACS index in predicting mortality among HIV-infected women. Providing treatment for depression and addressing economic and psychosocial instability in HIV-infected women would improve health and perhaps point to a broader public health approach to reducing HIV mortality.

Background: We previously reported that fracture incidence rates did not differ by HIV status among predominantly premenopausal Women's Interagency HIV Study participants. We now conduct a follow-up study with 5 additional observation years to further characterize fracture risk associated with HIV infection in women as they age., Methods: We measured time to first new fracture at any site in 2375 (1713 HIV-infected and 662 HIV-uninfected) Women's Interagency HIV Study participants, with median 10-year follow-up. Fractures were self-reported semiannually. Proportional hazards models assessed predictors of incident fracture., Results: At index visit, HIV-infected women were older [median age of 40 years (IQR: 34-46) vs. 35 (27-43), P < 0.0001] and more likely to be postmenopausal, hepatitis C virus infected, and weigh less than HIV-uninfected women. Among HIV-infected women, mean CD4 count was 480 cells per microliter and 63% were taking highly active antiretroviral therapy. Unadjusted incidence rates of any fracture were higher in HIV-infected than in HIV-uninfected women [2.19/100 person-years (py) vs. 1.54/100 py, P = 0.002]. In multivariate models, HIV status, older age, white (vs. black) race, prior fracture, history of cocaine use, and history of injection drug use were significant predictors of incident fracture. Among HIV-infected women, age, white race, prior fracture, smoking, and prior AIDS were predictors of new fracture., Conclusions: Middle-aged HIV-infected women had a higher adjusted fracture rate than HIV-uninfected women. Cocaine use and injection drug use were also associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture associated with cocaine use relates to increased rate of falls or direct effects on bone metabolism.

: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.

Introduction: The use of single-tablet antiretroviral therapy (ART) regimens and its implications on adherence among HIV-infected women have not been well described., Methods: Participants were enrolled in the Women's Interagency HIV Study, a longitudinal study of HIV infection in US women. We examined semiannual trends in single-tablet regimen use and ART adherence, defined as self-reported 95% adherence in the past 6 months, during 2006-2013. In a nested cohort study, we assessed the comparative effectiveness of a single-tablet versus a multiple-tablet regimen with respect to adherence, virologic suppression, quality of life, and AIDS-defining events, using propensity score matching to account for demographic, behavioral, and clinical confounders. We also examined these outcomes in a subset of women switching from a multiple- to single-tablet regimen using a case-crossover design., Results: We included 15,523 person-visits, representing 1727 women (53% black, 29% Hispanic, 25% IDU, median age 47). Use of single-tablet regimens among ART users increased from 7% in 2006% to 27% in 2013; adherence increased from 78% to 85% during the same period (both P < 0.001). Single-tablet regimen use was significantly associated with increased adherence (adjusted risk ratio: 1.05; 95% confidence interval: 1.03 to 1.08) and virologic suppression (risk ratio: 1.06; 95% confidence interval: 1.01 to 1.11), while associations with improved quality of life and fewer AIDS-defining events did not achieve statistical significance. Similar findings were observed among the subset of switchers., Conclusions: Single-tablet regimen use was associated with increased adherence and virologic suppression. Despite this, 15% of women prescribed ART were still not optimally adherent; additional interventions are needed to maximize therapeutic benefits.

Background: Stark racial/ethnic disparities in health outcomes exist among those living with HIV in the United States. One of 3 primary goals of the National HIV/AIDS Strategy is to reduce HIV-related disparities and health inequities., Methods: Using data from HIV-infected women participating in the Women's Interagency HIV Study from April 2006 to March 2011, we measured virologic failure (HIV RNA >200 copies/mL) after suppression (HIV RNA < 80 copies/mL) on highly active antiretroviral therapy. We identified predictors of virologic failure using discrete time survival analysis and calculated racial/ethnic-specific population-attributable fractions (PAFs)., Results: Of 887 eligible women, 408 (46%) experienced virologic failure during the study period. Hispanic and white women had significantly lower hazards of virologic failure than African American women [Hispanic hazard ratio, (HR) = 0.8, 95% confidence interval: (0.6 to 0.9); white HR = 0.7 (0.5 to 0.9)]. The PAF of virologic failure associated with low income was higher in Hispanic [adjusted hazard ratios (aHR) = 2.2 (0.7 to 6.5), PAF = 49%] and African American women [aHR = 1.8 (1.1 to 3.2), PAF = 38%] than among white women [aHR = 1.4 (0.6 to 3.4), PAF = 16%]. Lack of health insurance compared with public health insurance was associated with virologic failure only among Hispanic [aHR = 2.0 (0.9 to 4.6), PAF = 22%] and white women [aHR = 1.9 (0.7 to 5.1), PAF = 13%]. By contrast, depressive symptoms were associated with virologic failure only among African-American women [aHR = 1.6 (1.2 to 2.2), PAF = 17%]., Conclusions: In this population of treated HIV-infected women, virologic failure was common, and correlates of virologic failure varied by race/ethnicity. Strategies to reduce disparities in HIV treatment outcomes by race/ethnicity should address racial/ethnic-specific barriers including depression and low income to sustain virologic suppression.

Objective: HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed, and executive function in the multicenter Women's Interagency HIV Study., Methods: Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age = 42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test-Revised and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n = 140), former users (lifetime cocaine or heroin use but not in past 6 months, n = 651), and nonusers (no lifetime use of cocaine or heroin, n = 604)., Results: The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (P < 0.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared with nonuse) negatively impacted verbal learning and memory only in HIV-infected women (P < 0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test., Conclusions: The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.

Objectives: To evaluate the association of diet and physical activity with insulin resistance (IR) in HIV-infected and HIV-uninfected women., Methods: Cross-sectional analyses of summary dietary measures and physical activity intensity scores obtained from women enrolled in the San Francisco (n = 113) and Chicago (n = 65) Women's Interagency HIV Study (WIHS) sites. IR was estimated using the homeostasis model assessment (HOMA-IR). Stepwise regression models assessed the association of diet and physical activity with HOMA-IR after adjustment for demographic, behavioral, and clinical factors., Results: Compared with HIV-uninfected women, HIV-infected women were older and more likely to have health insurance. In multivariable analysis including all women, being from San Francisco ( P = 0.005), having a higher mean body mass index (BMI, P < 0.001), and having a higher percent kilocalories from sweets (P = 0.025) were associated with greater HOMA-IR; heavy intensity physical activity (P = 0.006) and annual household income more than $36,000 ( P = 0.02) was associated with a lower HOMA-IR. In analysis limited to HIV-infected women, having a higher body mass index (P < 0.001) and a history of protease inhibitor use (P = 0.002) were significantly associated with higher HOMA-IR; heavy intensity activity (P = 0.06) was marginally associated with lower HOMA-IR and being menopausal (P = 0.05) was marginally associated with higher HOMA-IR., Conclusions: Among urban women with or at risk for HIV-infection, heavy intensity physical activity was associated with lower HOMA-IR, whereas higher percent kilocalories from sweets were associated with higher HOMA-IR. Given the overall health benefits of physical activity and a diet low on sugar, these behaviors should be encouraged whenever possible.

Objective: HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women., Methods: In the Women's Interagency HIV Study, we measured concentrations of albumin-to-creatinine ratio, interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin from stored urine among 908 HIV-infected and 289 HIV-uninfected participants. Primary analyses used cystatin C-based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and 2 follow-up visits over 8 years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes., Results: Compared with the lowest tertiles, the highest tertiles of albumin-to-creatinine ratio (-0.15 mL/min per 1.73 m, P < 0.0001), IL-18 (-0.09 mL/min per 1.73 m, P < 0.0001) and KIM-1 (-0.06 mL/min per 1.73 m, P < 0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all 3 biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (relative risk = 1.40; 95% confidence interval: 1.04 to 1.89); ≥5% (1.88; 1.30 to 2.71); and ≥10% (2.16; 1.20 to 3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25 to 2.33) and 10% (1.78; 1.07 to 2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00 to 3.87)., Conclusions: Among HIV-infected women in the Women's Interagency HIV Study cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.

HIV risk behaviors, susceptibility to HIV acquisition, progression of disease after infection, and response to antiretroviral therapy all vary by age. In those living with HIV, current effective treatment has increased the median life expectancy to >70 years of age. Biologic, medical, individual, social, and societal issues change as one ages with HIV infection, but there has been only a small amount of research in this field. Therefore, the Office of AIDS Research of the National Institutes of Health commissioned a working group to develop an outline of the current state of knowledge and areas of critical need for research in HIV and Aging; the working groups' findings and recommendations are summarized in this report. Key overarching themes identified by the group included the following: multimorbidity, polypharmacy, and the need to emphasize maintenance of function; the complexity of assessing HIV versus treatment effects versus aging versus concurrent disease; the inter-related mechanisms of immune senescence, inflammation, and hypercoagulability; the utility of multivariable indices for predicting outcomes; a need to emphasize human studies to account for complexity; and a required focus on issues of community support, caregivers, and systems infrastructure. Critical resources are needed to enact this research agenda and include expanded review panel expertise in aging, functional measures, and multimorbidity, and facilitated use and continued funding to allow long-term follow-up of cohorts aging with HIV.

Background: In the early highly active antiretroviral therapy (HAART) era, kidney dysfunction was strongly associated with death among HIV-infected individuals. We re-examined this association in the later HAART period to determine whether chronic kidney disease remains a predictor of death after HAART initiation., Methods: To evaluate the effect of kidney function at the time of HAART initiation on time to all-cause mortality, we evaluated 1415 HIV-infected women initiating HAART in the Women's Interagency HIV Study. Multivariable proportional hazards models with survival times calculated from HAART initiation to death were constructed; participants were censored at the time of the last available visit or December 31, 2006., Results: Chronic kidney disease (estimated glomerular filtration rate less than 60 mL/min/1.73 m) at HAART initiation was associated with higher mortality risk adjusting for age, race, hepatitis C serostatus, AIDS history, and CD4 cell count (hazard ratio 2.23, 95% confidence interval: 1.45-3.43). Adjustment for hypertension and diabetes history attenuated this association (hazard ratio = 1.89, confidence interval: 0.94-3.80). Lower kidney function at HAART initiation was weakly associated with increased mortality risk in women with prior AIDS (hazard ratio = 1.09, confidence interval: 1.00-1.19, per 20% decrease in estimated glomerular filtration rate)., Conclusions: Kidney function at HAART initiation remains an independent predictor of death in HIV-infected individuals, especially in those with a history of AIDS. Our study emphasizes the necessity of monitoring kidney function in this population. Additional studies are needed to determine mechanisms underlying the increased mortality risk associated with chronic kidney disease in HIV-infected persons.

Objectives: Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy., Methods: Urinalysis for proteinuria and semiquantitative testing for microalbuminuria were performed in specimens from 2 consecutive visits in 1547 HIV-infected women enrolled in the Women's Interagency HIV Study in 1994-1995. Time to death was modeled using proportional hazards analysis., Results: Compared with women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with 1 (HR: 3.4; 95% CI: 2.2 to 5.2) or 2 specimens positive for either proteinuria or microalbuminuria (HR: 3.9; 95% CI: 2.1 to 7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR: 5.8; 95% CI: 3.4 to 9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death., Conclusions: We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.

Objective: To compare sexual problems among HIV-positive and HIV-negative women and describe clinical and psychosocial factors associated with these problems., Design: Data were collected during a study visit of the Women's Interagency HIV Study (WIHS). The WIHS studies the natural and treated history of HIV among women in the United States., Methods: Between October 01, 2006, and March 30, 2007, 1805 women (1279 HIV positive and 526 HIV negative) completed a study visit that included administration of the Female Sexual Function Index. In addition, the visit included completion of standardized interviewer-administered surveys, physical and gynecological examinations, and blood sample collection., Results: Women with HIV reported greater sexual problems than did those without HIV. Women also reported lower sexual function if they were classified as menopausal, had symptoms indicative of depression, or if they reported not being in a relationship. CD4 cell count was associated with Female Sexual Function Index scores, such that those with CD4

Background: Opiate use is common in HIV-infected and hepatitis C virus (HCV)-infected individuals, however, its contribution to the risk of diabetes mellitus is not well understood., Methods: Prospective study of 1713 HIV-infected and 652 HIV-uninfected participants from the Women's Interagency HIV Study between October 2000 and March 2006. Diabetes defined as fasting glucose > or =126 mg/dL, self report of diabetes medication use, or confirmed diabetes diagnosis. Opiate use determined using an interviewer-administered questionnaire. Detectable plasma HCV RNA confirmed HCV infection., Results: Current opiate users had a higher prevalence of diabetes (15%) than nonusers (10%, P = 0.03), and a higher risk of incident diabetes (adjusted relative hazard: 1.58, 95% confidence interval: 1.01 to 2.46), after controlling for HCV infection, HIV/antiretroviral therapy status, and diabetes risk factors including age, race/ethnicity, family history of diabetes, and body mass index. HCV infection was also an independent risk factor for diabetes (adjusted relative hazard: 1.61, 95% confidence interval: 1.02 to 2.52). HCV-infected women reporting current opiate use had the highest diabetes incidence (4.83 cases per 100 person-years)., Conclusions: Among women with or at-risk for HIV, opiate use is associated with increased diabetes risk independently of HCV infection. Diabetic screening should be part of care for opiate users and those infected with HCV.

Background: Low bone mineral density (BMD) has been reported in HIV+ women, but less is known about the longitudinal evolution of BMD and fracture incidence., Methods: In 100 HIV+ and 68 HIV- premenopausal women in the Women's Interagency HIV Study, BMD was measured by dual energy x-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) at index visit and after a median of 2.5 years., Results: In HIV+ women, BMD at index visit was normal but 5% lower at the LS and FN than in HIV- women. Annual percent decrease in BMD did not differ between HIV+ and HIV- women at the LS (-0.8% +/- 0.2% vs -0.4% +/- 0.2%, P = 0.20) or FN (-0.8% +/- 0.3% vs -0.6% +/- 0.3%, P = 0.56) and remained similar after adjustment for age, weight, and BMD at index visit. Among HIV+ women, bone loss was associated with vitamin D deficiency and opiate use but not with use or class of antiretrovirals. Incidence of self-reported fracture was 0.74 per 100 person-years in HIV+ women and similar in HIV- women., Conclusions: In premenopausal HIV+ women, index BMD was lower than comparable HIV- women; however, rates of bone loss at the LS and FN were similar over 2.5 years of observation, irrespective of antiretroviral therapy.

Objective: The use of hormonal contraception (HC) is increasing in HIV-infected women. Both HC and HIV infection have been associated with adverse metabolic outcomes. We investigated the association of progestin-only and combined (estrogen/progestin) HC with disorders of glucose and lipid metabolism in HIV-infected and uninfected women., Methods: Linear mixed models evaluated the association of HC type with fasting high density lipoprotein, low density lipoprotein, triglycerides, the homeostasis model assessment estimate of insulin resistance (HOMA-IR), and glucose in 885 HIV-infected and 408 HIV-uninfected women from the Women's Interagency HIV Study seen between October 2000 and September 2005., Results: Compared with non-HC users, progestin-only HC was independently associated with lower HDL [-3 mg/dL; 95% confidence interval (CI) -5, -1 in HIV-infected and -6 mg/dL; 95% CI: -9, -3 in HIV-uninfected women] and greater HOMA-IR (+0.86; 95% CI: 0.51-1.22 and +0.56; 95% CI: 0.12-1.01). Combined HC was associated with higher HDL (+5 mg/dL; 95% CI: 2-7 and +5 mg/dL; 95% CI: 3-7)., Conclusions: HIV-infected women using progestin-only HC have lower HDL and greater HOMA-IR than HIV-infected non-HC users. Combined HC may be preferred in HIV-infected women of reproductive age at risk for cardiovascular disease, but interactions with antiretroviral therapy that may impair contraceptive efficacy have been reported. Alternative HC methods that minimize adverse outcomes but maintain efficacy require further study.

Background: To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10-year period among participants in the Women's Interagency HIV Study, a representative US cohort., Methods: Deaths were ascertained by National Death Index Plus match, and causes of death determined by death certificate., Results: From 1995 through 2004, 710 of 2792 HIV-infected participants died. During this interval, the standardized mortality ratio fell from a high of 24.7 in 1996 to a plateau with a mean of 10.3 from 2001 to 2004. Over the decade, deaths from non-AIDS causes increased and accounted for the majority of deaths by 2001-2004. The most common non-AIDS causes of death were trauma or overdose, liver disease, cardiovascular disease, and malignancy. Independent predictors of mortality besides HIV-associated variables were depressive symptoms and active hepatitis B or C. Women who were overweight or obese were significantly less likely to die of AIDS than women of normal weight., Conclusions: In the Women's Interagency HIV Study, the death rate has plateaued in recent years. Although HIV-associated factors predicted AIDS and non-AIDS deaths, other treatable conditions predicted mortality. Further gains in reducing mortality among HIV-infected women may require broader access to therapies for depression, viral hepatitis, and HIV itself.

Objectives: To assess the prevalence of metabolic syndrome (MetSynd) among participants of the Women's Interagency HIV Study and to describe the association of MetSynd with HIV infection, antiretroviral therapies, and sociodemographic factors., Methods: Prevalence of MetSynd, defined by updated Adult Treatment Panel III guidelines, was assessed among 2393 (1725 seropositive and 668 seronegative) participants from the Women's Interagency HIV Study seen between October 2000 and October 2004., Results: HIV-1 infection was independently associated with MetSynd [33% vs 22%, P<0.0001 in HIV-seropositive compared with HIV-seronegative women; adjusted odds ratio (OR) 1.79 (95% confidence interval 1.48, 2.16)]. HIV-infected women had higher mean triglyceride (154 vs 101 mg/dL, P<0.0001) and lower mean high-density lipoprotein cholesterol levels (46 vs 55 mg/dL, P<0.0001). Most notable factors associated with higher prevalence of MetSynd among HIV-infected women included older age (OR=1.38 per 5 year increase, P<0.0001); higher body mass index; current smoking; HIV-1 RNA (OR=1.36, P=0.019, for >50,000 vs <80 copies/mL); and use of stavudine (OR=1.28, P=0.009). Nevirapine use was protective (OR=0.75, P=0.016). There was no significant association of MetSynd with ritonavir-boosted protease inhibitors (OR=1.15, P=0.134)., Conclusions: MetSynd is more prevalent in HIV-seropositive than HIV-seronegative women. This increased prevalence was due to dyslipidemias rather than higher blood pressure, glucose, or waist circumference.

Background: Anemia is common in HIV-infected individuals and may be associated with decreased survival., Objective: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women., Methods: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period., Results: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001)., Conclusions: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.

Objective: To estimate the incidence of lipoatrophy and lipohypertrophy among HIV-infected and HIV-uninfected women from the Women's Interagency HIV Study., Design: Eight hundred fifteen women with semiannual data on self-report of bidirectional change in body fat, anthropometric measurements, weight, and bioelectric impedance analysis were included in a 30-month incidence analysis., Methods: Lipoatrophy and lipohypertrophy in both peripheral (arms, legs, and buttocks) and central (waist, chest, and upper back) sites were defined by self-report of either a decrease or an increase in a body fat region over the previous 6 months that was confirmed by a corresponding change in anthropometric measurement., Results: Weight and total body fat increased in HIV-uninfected women but remained stable in HIV-infected women over 30 months. Among HIV-infected women, the incidence of peripheral (relative hazard, 2.1; 95% confidence interval [CI], 1.4-3.3) and central (relative hazard, 1.9; 95% CI, 1.2-2.8) lipoatrophy was about double that among HIV-uninfected women, after adjustment for age and race. The incidence of peripheral lipohypertrophy appeared lower among HIV-infected women than among HIV-uninfected women (relative hazard, 0.8; 95% CI, 0.6-1.1), while the incidence of central lipohypertrophy did not differ by HIV status. Of HIV-infected women with 2 of 4 lipodystrophy outcomes, most (81%) had combined peripheral and central lipoatrophy or combined peripheral and central lipohypertrophy. Only 14% of these women had both peripheral lipoatrophy and central lipohypertrophy., Conclusions: These prospective data suggest that lipoatrophy, affecting both peripheral and central sites, predominates in HIV-infected women. The simultaneous occurrence of peripheral lipoatrophy and central lipohypertrophy was uncommon.

This study examines the effects of depressive symptoms and mental health quality of life on utilization of highly active antiretroviral therapy (HAART) among HIV-seropositive women. Data were collected biannually from 1996 through 1998 in a prospective cohort study. Women reported use of antiretroviral therapy, health and mental health status, demographics, and social and behavioral factors; CD4 count and viral load also were assessed. Random effects regression models estimated the longitudinal effects of depressive symptoms and mental health quality of life on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load, symptom presence), demographics (race, age, education), behavioral factors (drug/alcohol use, clinical trials participation), service features (insurance status, mental health service utilization), and study site. High levels of depressive symptoms and poor mental health quality of life were found, and they significantly reduced the probability of HAART utilization. Receiving mental health services significantly increased the probability of utilizing HAART. HIV-seropositive women characterized as being in poor mental health were less likely to use HAART, whereas those receiving treatment of mental health difficulties were more likely to use HAART. These findings suggest that efforts to enhance women's access to psychological treatment may increase their use of the latest HIV therapies.