9The Women's Interagency HIV Study (WIHS) is an ongoing long-term observational study of 3,772 women who are either infected with human immunodeficiency virus (HIV) or considered to be at risk for acquiring HIV. Since 1994, the WIHS (pronounced like "wise") has developed a large database and specimen repository that serve as resources for WIHS investigators as well as for nonaffiliated researchers working on HIVrelated or HIV coinfection issues. The purpose of this report is to update researchers on the progress of the WIHS and to provide information on WIHS resources, the methods by which they were obtained, and background for any new potential researchers interested in conducting collaborative research through shared use of these resources. BACKGROUND

Objective: In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2).Methods: From 2009 participants from the Women's Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional. Results:The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. Conclusions:The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in wellmatched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition. Compared to HIV-infected men, HIV-infected women may be at greater risk for cognitive decline due to a higher prevalence of risk factors common in predominantly minority, urbandwelling women, such as poverty, low literacy levels, low education, substance abuse, poor mental health, early life stressors and trauma, barriers to health care service utilization, and environmental exposures.1,2 These factors might contribute to low cognitive reserve and confer increased risks of cognitive dysfunction. Several studies have examined cognition in HIVinfected women, 3-11 but the maximum sample size has been 237. Larger studies are needed to understand the determinants and patterns of cognitive function in HIV-infected women.The Women's Interagency HIV Study (WIHS) is the largest longitudinal study of the natural and treated history of HIV infection and clinical outcomes in women residing in the United States.12,13 Here we present the first findings from the largest comprehensive cohort study of cognitive function in HIV-infected (n 5 1,019) and demographically similar HIVuninfected women (n 5 502). Our first aim was to investigate the association between HIV status and cognition in relation to other determinants of cognition. We predicted that low socioeconomic status, low reading level, illicit substance use, and depressive symptoms would contribute to decrements across a range of cognitive domains, and would more strongly influence cognition in HIV-infected wo...

In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women’s Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (p<0.01) and memory (p<0.001), as well as attention (p=0.02). Regardless of HIV status, high stress was associated with poorer performance in those cognitive domains (p’s< 0.05) as well as processing speed (p=0.01) and executive function (p<0.01). A significant HIV by stress interaction was found only for the verbal memory domain (p=0.02); among HIV-infected women only, high stress was associated with lower performance (p’s<0.001). That association was driven by the delayed verbal memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.

Objective: The objective was to assess study retention and attendance for two recruitment waves of participants in the Women's Interagency HIV Study (WIHS). Methods: The WIHS, a prospective study at six clinical centers in the United States, has experienced two phases of participant recruitment. In phase one, women were screened and enrolled at the same time, and in phase two, women were screened and enrolled at separate visits. Compliance with study follow-up was evaluated by examining semiannual study retention and visit attendance. Results: After 10 study visits, the retention rate in the original recruits (enrolled in 1994-1995) was 83% for the HIV-infected women and 69% for the HIV-uninfected women compared with 86% and 86%, respectively, in the new recruits (enrolled in 2001-2002). In logistic regression analysis of the HIV-infected women, factors associated with early (visits 2 and 3) nonattendance were temporary housing, moderate alcohol consumption, use of crack=cocaine=heroin, having a primary care provider, WIHS site of enrollment, lower CD4 cell count, and higher viral load. Among HIV-uninfected women, the factors associated with early nonattendance were recruitment into the original cohort, household income !$12,000 per year, temporary housing, unemployment, use of crack=cocaine=heroin, and WIHS site of enrollment. Factors associated with nonattendance at later visits (7-10) among HIV-infected participants were younger age, white race, not having a primary care provider, not having health insurance, WIHS site of enrollment, higher viral load, and nonattendance at a previous visit. In HIV-uninfected participants, younger age, white race, WIHS site of enrollment, and nonattendance at a previous visit were significantly associated with nonattendance at later visits. Conclusions: Preventing early loss to follow-up resulted in better study retention early, but late loss to follow-up may require different retention strategies.

Cognitive difficulties remain among HIV+ women despite persistent viral suppression. In some instances, VS women are worse than NVS women, reinforcing the need for novel adjunctive therapies to attenuate cognitive problems.

ObjectiveTo review the incidence of respiratory conditions and their effect on mortality in HIV-infected and uninfected individuals prior to and during the era of highly active antiretroviral therapy (HAART).DesignTwo large observational cohorts of HIV-infected and HIV-uninfected men (Multicenter AIDS Cohort Study [MACS]) and women (Women’s Interagency HIV Study [WIHS]), followed since 1984 and 1994, respectively.MethodsAdjusted odds or hazards ratios for incident respiratory infections or non-infectious respiratory diagnoses, respectively, in HIV-infected compared to HIV-uninfected individuals in both the pre-HAART (MACS only) and HAART eras; and adjusted Cox proportional hazard ratios for mortality in HIV-infected persons with lung disease during the HAART era.ResultsCompared to HIV-uninfected participants, HIV-infected individuals had more incident respiratory infections both pre-HAART (MACS, odds ratio [adjusted-OR], 2.4; 95% confidence interval [CI], 2.2–2.7; p<0.001) and after HAART availability (MACS, adjusted-OR, 1.5; 95%CI 1.3–1.7; p<0.001; WIHS adjusted-OR, 2.2; 95%CI 1.8–2.7; p<0.001). Chronic obstructive pulmonary disease was more common in MACS HIV-infected vs. HIV-uninfected participants pre-HAART (hazard ratio [adjusted-HR] 2.9; 95%CI, 1.02–8.4; p = 0.046). After HAART availability, non-infectious lung diseases were not significantly more common in HIV-infected participants in either MACS or WIHS participants. HIV-infected participants in the HAART era with respiratory infections had an increased risk of death compared to those without infections (MACS adjusted-HR, 1.5; 95%CI, 1.3–1.7; p<0.001; WIHS adjusted-HR, 1.9; 95%CI, 1.5–2.4; p<0.001).ConclusionHIV infection remained a significant risk for infectious respiratory diseases after the introduction of HAART, and infectious respiratory diseases were associated with an increased risk of mortality.

Design Multi-center, prospective cohort study Methods Every two years between 2009 and 2013 (3 times), 646 HIV+ and 300 demographically-similar HIV-uninfected (HIV-) women from the Women’s Interagency HIV Study completed neuropsychological (NP) testing and questionnaires measuring PRFs (perceived stress, post-traumatic stress disorder (PTSD) symptoms, depressive symptoms). Using mixed-effects regressions, we examined separate and interactive associations between HIV-serostatus and PRFs on performance over time. Results HIV+ and HIV- women had similar rates of PRFs. Fluency was the only domain where performance over time depended on the combined influence of HIV-serostatus and stress or PTSD (p’s<0.05); not depression. In HIV, higher stress and PTSD were associated with a greater cognitive decline in performance (p’s<0.05) versus lower stress and PTSD. Irrespective of time, performance on learning and memory depended on the combined influence of HIV-serostatus and stress or PTSD (p’s≤0.05). In the context of HIV, stress and PTSD were negatively associated with performance. Effects were pronounced on learning among HIV+ women without effective treatment or viral suppression. Regardless of time or HIV-serostatus, all PRFs were associated with lower speed, global NP, and executive function. Conclusions More than depression, perceived stress and PTSD symptoms are treatment targets to potentially improve fluency, learning, and memory in women living with HIV particularly when HIV treatment is not optimal.

The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV−) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV− women. HIV infection was not associated with a probable PTSD diagnosis (17 % HIV+, 16 % HIV−; p=0.49) but was associated with lower verbal learning (p<0.01) and memory scores (p<0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p<0.01) and memory (p<0.01) and psychomotor speed (p<0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p= 0.03). Among women with probable PTSD, HIV− women performed worse than HIV+ women on fine motor skills (p=0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p= 0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.