Effects of Antiretroviral Therapy and Depressive Symptoms on All-Cause Mortality Among HIV-Infected Women

Abstract

Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998-2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women.

Keywords: HIV; antiretroviral therapy; cohort studies; depression; marginal structural models; mortality; proportional hazards models; women.

Figure 1.

Joint exposure status of antiretroviral therapy (ART) initiation and depressive symptoms in the Women's Interagency HIV Study, United States, 1998–2011. The proportion of women with depressive symptoms who had initiated ART is represented by the black shaded area, women without depressive symptoms who had initiated ART by dark gray, women with depressive symptoms who had not initiated ART by light gray, and women without depressive symptoms who had not initiated ART by white.

Figure 2.

Effects of antiretroviral therapy (ART) initiation and depressive symptoms on cumulative mortality in the Women's Interagency HIV Study, United States, 1998–2011. Women who had not initiated ART are represented by the solid line and women who had initiated ART by the dashed line (A). Women experiencing depressive symptoms are represented by the solid line and women not experiencing depressive symptoms by the dashed line (B). Weighted models adjusted for age at enrollment, race, CD4 cell count, log₁₀ HIV RNA, baseline CD4 cell count, and baseline log₁₀ HIV RNA. Weights for depressive symptoms also adjusted for depressive symptoms at the previous visit.

Figure 3.

Joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on cumulative mortality in the Women's Interagency HIV Study, United States, 1998–2011. Women with depressive symptoms who had not initiated ART are represented by the solid black line, women with depressive symptoms who had initiated ART by the solid gray line; women without depressive symptoms who had not initiated ART by the dashed black line, and women without depressive symptoms who had initiated ART by the dashed gray line. Weighted models adjusted for age at enrollment, race, CD4 cell count, log₁₀ HIV RNA, baseline CD4 cell count, and baseline log₁₀ HIV RNA. Weights for depressive symptoms also adjusted for depressive symptoms at the previous visit.