Quantifying an Adherence Path-Specific Effect of Antiretroviral Therapy in the Nigeria PEPFAR Program

• Activity Number: 122
• Type: Topic Contributed
• Date/Time: Monday, August 10, 2015 : 8:30 AM to 10:20 AM
• Sponsor: Health Policy Statistics Section
• Author(s): Caleb Miles* and Ilya Shpitser and Phyllis Kanki and Seema Meloni and Eric Tchetgen Tchetgen
• Companies: and University of Southampton and Harvard School of Public Health and Harvard School of Public Health and Harvard University
• Keywords: HIV ; mediation ; nonparametric identification ; unobserved confounding ; robustness

Abstract

Since the early 2000s, evidence has accumulated for a significant differential effect of first-line antiretroviral therapy (ART) regimens on HIV treatment outcomes. This finding was replicated in our data from the Harvard President's Emergency Plan for AIDS Relief (PEPFAR) program in Nigeria. Investigators were interested in understanding the mechanisms through which one regimen outperforms another, particularly via adherence. This amounts to a mediation question with adherence playing the role of mediator. Existing mediation analysis results, however, have relied on an assumption of no exposure-induced confounding of the intermediate variable, and generally require an assumption of no unmeasured confounding for nonparametric identification. Both assumptions are violated by the presence of drug toxicity. In this paper, we relax these assumptions and show that certain path-specific effects remain identified under weaker conditions. We focus on the path-specific effect solely mediated by adherence and not by toxicity and propose a suite of estimators for this effect. We illustrate with simulations and present results from a study applying the methodology to the Harvard PEPFAR data.