The Impact of Cumulative Depression Along the HIV Care Continuum in Women Living with HIV during the Era of Universal Antiretroviral Treatment

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

Use of Nonantiretroviral Medications That May Impact Neurocognition: Patterns and Predictors in a Large, Long-Term HIV Cohort Study

Background: Neurocognitive impairment is a frequent and often disabling comorbidity of HIV infection. In addition to antiretroviral therapies, individuals with HIV infection may commonly use nonantiretroviral medications that are known to cause neurocognitive adverse effects (NC-AE). The contribution of NC-AE to neurocognitive impairment is rarely considered in the context of HIV and could explain part of the variability in neurocognitive performance among individuals with HIV. Setting: Women’s Interagency HIV Study, a prospective, multisite, observational study of US women with and without HIV. Methods: After a literature review, 79 medications (excluding statins) with NC-AE were identified and reported by Women’s Interagency HIV Study participants. We examined factors associated with self-reported use of these medications over a 10-year period. Generalized estimating equations for binary outcomes were used to assess sociodemographic, behavioral, and clinical characteristics associated with NC-AE medication use. Results: Three thousand three hundred women (71% with HIV) and data from ~42,000 visits were studied. HIV infection was associated with NC-AE medication use (odds ratio = 1.52; 95% confidence interval: 1.35 to 1.71). After adjustment for HIV infection status, other predictors of NC-AE medication use included having health insurance, elevated depressive symptoms, prior clinical AIDS, noninjection recreational drug use, and an annual household income of <$12,000 (Ps < 0.004). NC-AE medication use was less likely among women who drank 1–7 or 8–12 alcoholic drinks/week (vs. abstaining) (P < 0.04). Conclusions: HIV infection was associated with NC-AE medication use, which may influence determinations of HIV-associated neurocognitive impairment. Providers should consider the impact of NC-AE medications when evaluating patients with HIV and concurrent neurocognitive symptoms

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

Cumulative burden of depression and all-cause mortality in women living with human immunodeficiency virus

Background Research linking depression to mortality among people living with human immunodeficiency virus (PLWH) has largely focused on binary "always vs never" characterizations of depression. However, depression is chronic and is likely to have cumulative effects on mortality over time. Quantifying depression as a cumulative exposure may provide a better indication of the clinical benefit of enhanced depression treatment protocols delivered in HIV care settings. Methods Women living with HIV (WLWH), naive to antiretroviral therapy, from the Women's Interagency HIV Study were followed from their first visit in or after 1998 for up to 10 semiannual visits (5 years). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D) scale. An area-under-the-curve approach was used to translate CES-D scores into a time-updated measure of cumulative days with depression (CDWD). We estimated the effect of CDWD on all-cause mortality using marginal structural Cox proportional hazards models. Results Overall, 818 women contributed 3292 woman-years over a median of 4.8 years of follow-up, during which the median (interquartile range) CDWD was 366 (97-853). Ninety-four women died during follow-up (2.9 deaths/100 woman-years). A dose-response relationship was observed between CDWD and mortality. Each additional 365 days spent with depression increased mortality risk by 72% (hazard ratio, 1.72; 95% confidence interval, 1.34-2.20). Conclusions In this sample of WLWH, increased CDWD elevated mortality rates in a dose-response fashion. More frequent monitoring and enhanced depression treatment protocols designed to reduce CDWD may interrupt the accumulation of mortality risk among WLWH

Modeling Adaptation Effects in fMRI Analysis

The standard general linear model (GLM) for rapid event-related fMRI design protocols typically ignores reduction in hemodynamic responses in successive stimuli in a train due to incomplete recovery from the preceding stimuli. To capture this adaptation effect, we incorporate a region-specific adaptation model into GLM. The model quantifies the rate of adaptation across brain regions, which is of interest in neuroscience. Empirical evaluation of the proposed model demonstrates its potential to improve detection sensitivity. In the fMRI experiments using visual and auditory stimuli, we observed that the adaptation effect is significantly stronger in the visual area than in the auditory area, suggesting that we must account for this effect to avoid bias in fMRI detection