One-third (1/3) of AIDS patients in Haiti present with chronic diarrhea. AIDS patients with chronic diarrhea at initiation of antiretroviral therapy have higher mortality rates than AIDS patients initiated on antiretroviral therapy without diarrhea. We hypothesize that tropical AIDS diarrhea causes malabsorption of antiretroviral drugs and sub-optimal drug levels that result in virologic failure and the development of HIV genomic drug resistance.
The specific aims of this research proposal are:
Aim 1) To determine the effect of tropical AIDS diarrhea on absorption of antiretroviral drugs, virologic response to therapy, and the development of HIV genomic drug resistance.
Aim 2) To identify other co-factors that may relate to response to antiretroviral therapy in AIDS patients with tropical diarrhea including etiologic agent of diarrhea, nutritional status, drug toxicity, and adherence. A case-control study will be conducted to compare plasma and intracellular antiretroviral drug concentrations, decrease in viral load at 4 weeks, virologic failure at 48 weeks, and the incidence of HIV genomic drug resistance mutations at 48 weeks between 50 AIDS patients with chronic diarrhea and 50 AIDS patients without diarrhea. Cases will be antiretroviral drug naive AIDS patients with chronic diarrhea (3 or more liquid stools/day for > 3 weeks) who are initiating Haiti's first line regimen of AZT, 3TC, and efavirenz. Controls will be antiretroviral drug naive AIDS patients matched to cases for age, sex, and CD4 count who do not have diarrhea and who are initiating the same drug regimen. The study will be conducted at the GHESKIO Center in Port au Prince, which has conducted clinical research for 20 years and is currently conducting 2 NIH sponsored HIV vaccine trials, an ACTG clinical trial, and CIPRA AIDS research. Drug malabsorption in AIDS patients with chronic diarrhea may result in sub-optimal drug levels, high rates of treatment failure, and the development of HIV drug resistance. This exploratory research proposal will bring together a unique collaboration of investigators from Cornell University, Haiti, and other US universities to provide urgently needed information on the effect of AIDS diarrhea on antiretroviral drug absorption.
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