A marginal structural model to estimate the causal effect of antidepressant medication treatment on viral suppression among homeless and marginally housed persons with HIV

Abstract

Context: Depression strongly predicts nonadherence to human immunodeficiency virus (HIV) antiretroviral therapy, and adherence is essential to maintaining viral suppression. This suggests that pharmacologic treatment of depression may improve virologic outcomes. However, previous longitudinal observational analyses have inadequately adjusted for time-varying confounding by depression severity, which could yield biased estimates of treatment effect. Application of marginal structural modeling to longitudinal observation data can, under certain assumptions, approximate the findings of a randomized controlled trial.

Objective: To determine whether antidepressant medication treatment increases the probability of HIV viral suppression.

Design: Community-based prospective cohort study with assessments conducted every 3 months.

Setting: Community-based research field site in San Francisco, California.

Participants: One hundred fifty-eight homeless and marginally housed persons with HIV who met baseline immunologic (CD4+ T-lymphocyte count, <350/μL) and psychiatric (Beck Depression Inventory II score, >13) inclusion criteria, observed from April 2002 through August 2007.

Main outcome measures: Probability of achieving viral suppression to less than 50 copies/mL. Secondary outcomes of interest were probability of being on an antiretroviral therapy regimen, 7-day self-reported percentage adherence to antiretroviral therapy, and probability of reporting complete (100%) adherence.

Results: Marginal structural models estimated a 2.03 greater odds of achieving viral suppression (95% confidence interval [CI], 1.15-3.58; P = .02) resulting from antidepressant medication treatment. In addition, antidepressant medication use increased the probability of antiretroviral uptake (weighted odds ratio, 3.87; 95% CI, 1.98-7.58; P < .001). Self-reported adherence to antiretroviral therapy increased by 25 percentage points (95% CI, 14-36; P < .001), and the odds of reporting complete adherence nearly doubled (weighted odds ratio, 1.94; 95% CI, 1.20-3.13; P = .006).

Conclusions: Antidepressant medication treatment increases viral suppression among persons with HIV. This effect is likely attributable to improved adherence to a continuum of HIV care, including increased uptake and adherence to antiretroviral therapy.

Figure 1. Model of the causal pathway between antidepressant medication use and viral suppression, with time-varying confounding by indication

Depression severity confounds the observed relationship between antidepressant medication use and viral suppression, because patients with more severe depression are more likely to be prescribed antidepressant medication and are also more likely to have worsened virologic outcome. Over the course of longitudinal follow up, depression severity may be improved by past treatment with antidepressant medication. It is therefore part of the causal pathway of interest (leading from antidepressant medication treatment to improved virologic outcome). Conventional statistical adjustment, i.e., including depression severity as a time-dependent variable in a regression model, may bias the estimated treatment effect towards the null by conditioning on part of the effect of interest.