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Impact of Malnutrition on HIV Treatment Failure in Resource-limited Settings
Highly active antiretroviral therapy (HAART) has reduced morbidity and mortality among HIV-infected persons worldwide. However, early treatment failure (i.e. WHO stage 3 or 4 illnesses or death during the first 24 months of HAART) is more than 3-fold higher in resource limited settings (RLS) than in resource-rich settings. Early treatment failure is associated with low CD4 count, low body mass index, and anemia, but these markers are nonspecific and could reflect advanced HIV, co-infections, and/or malnutrition.
The relative contribution of malnutrition to early treatment failure in RLS is unknown. Up to 40% of adults in RLS are malnourished due to protein-energy, iron or iron-deficiency anemia, or other micronutrient deficiencies, which are associated with immune dysfunction and increased morbidity and mortality. However, the significance of this malnutrition in HIV-infected persons initiating HAART in RLS is unclear. In addition to immune dysfunction, this malnutrition has been associated with impaired gut integrity, increased microbial translocation and immune activation. Recently, chronic HIV infection has also been associated with a “leaky gut” and systemic immune activation. High levels of immune activation result in impaired immune restoration with HAART and HIV disease progression.
Therefore, we hypothesize that baseline malnutrition is predictive of early treatment failure among HIV-infected adults in RLS and that early treatment failure is related to the synergistic deleterious effects of HIV and malnutrition on gut mucosal integrity leading to increased systemic immune activation. To address our hypotheses, our international team, which includes leaders in HIV, immunology, statistics and research, will utilize data and cryopreserved samples collected as part of an ongoing trial conducted by the Adults AIDS Clinical Trial Group (ACTG 5175). This NIH-funded study is evaluating the efficacy of HAART among 1571 HIV-infected adults in 8 RLS countries (South Africa, Zimbabwe, Malawi, Thailand, India, Brazil, Peru, Haiti) and the United States.