Good adherence to anti-retroviral therapy (ART) is widely accepted as a key factor for sustained viral suppression of human immunodeficiency virus (HIV), and is often considered a prerequisite for maintenance on a prescribed drug regimen and optimal patient outcomes. However, the extent to which adherence to a given choice of therapy (relative to another therapy), contributes to virologic failure is complex and stll poorly understood, and is a pressing mediation question in HIV research. Understanding this issue is particularly important in resource poor settings where ART regimen options are limited and adherence to lifelong multi- drug daily dosing is challenging but necessary. In such settings, quantifying to what degree differential rates of virologic failure are due to difference in adherence rates between therapies would inform the extent to which failure rates could be improved by programs that increase adherence rates for certain ARTs, rather than improving ART regimens themselves. Such adherence interventions have been very successful in the treatment of tuberculosis and are considered important in the treatment of HIV. Unfortunately, traditional approaches to mediation analysis assume static settings with no unobserved confounding, and are thus not suited for analysis of complex longitudinal data typically encountered in observational studies of HIV. Our plan is to remedy this deficiency using recent developments in causal inference based on potential outcomes and graphical models, and modern semi-parametric theory.

Public Health Relevance

Patient outcome of a treatment regimen is often governed not only by the quality of the treatment itself, but also by patient adherence to the regimen. We plan to develop and apply modern techniques of mediation analysis to determine how much of the regimen's success is due to treatment quality, and how much to patient adherence to the regimen. We plan to apply our analysis to improving outcomes of HIV patients in Nigeria.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI104459-02
Application #
8666718
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Mckaig, Rosemary G
Project Start
2013-06-01
Project End
2018-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
2
Fiscal Year
2014
Total Cost
$403,750
Indirect Cost
$153,750
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
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