Subtype and CCR5/CXCR4 Tropism in HIV-1 Infected Ugandan Children

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Investigator: Theodore D. Ruel, MD

Location(s): Uganda

Parent Project: UCSF-Gladstone Center for AIDS Research (CFAR)

Description

Alcohol is the most commonly used recreational drug in sub-Saharan Africa, and Uganda has the highest rate of per capita alcohol consumption in the world. Alcohol consumption is recognized as a predictor of sexual risk behavior and thus HIV transmission and acquisition in sub-Saharan Africa, yet the effect of alcohol on HIV treatment success has not been studied in this setting. HIV antiretroviral therapy (ART) is increasing rapidly in sub-Saharan Africa, and has greatly decreased HIV morbidity and mortality. However, HIV treatment failure, defined as detectable HIV virus after six months of ART, occurs in 10-20% of patients and has a significant individual and public health cost given limited treatment options in sub-Saharan Africa. Drug and alcohol use have been important causes of treatment failure in resource rich countries, due to both behavioral and biologic mechanisms. However, alcohol consumption has not been studied as a cause of treatment failure in sub-Saharan Africa, possibly because alcohol consumption is challenging to measure. It is difficult to define a "standard drink unit", because most alcoholic drinks in this region are "home brews" which may vary widely in their concentration and drink sizes, and some alcoholic beverages are consumed communally from a large pot. In addition, alcohol consumption may be under-reported. Persons hoping to receive HIV treatment are counseled to refrain from drinking, and therefore may be less likely to report their alcohol use or more likely to minimize their consumption. Novel biomarkers have been developed over the past ten years to identify metabolites of alcohol that may be detected for extended periods of time after alcohol itself has left the body. We propose to use these biomarkers to examine the effects of alcohol consumption on HIV outcomes, by leveraging an established prospective cohort study of HIV treatment outcomes in Uganda. We will conduct a nested case-control study within the UARTO study, with 45 cases and 45 controls, to examine the association between alcohol consumption and HIV treatment failure. Cases will be persons failing ART, i.e., those with detectable HIV viral loads after six months of treatment. Controls will be those with undetectable viral load after six months of treatment and will be matched on sex and duration of ART. We will examine both heavy alcohol use and recent alcohol use as predictors of treatment failure. We will also examine whether lower treatment adherence among drinkers mediates the effect of alcohol on treatment failure, or whether the alcohol has a direct biologic effect on HIV treatment outcome. We will also examine whether alcohol consumption predicts viral resistance. Last, we will compare self-reported alcohol use to the biomarker results to quantify under-reporting of alcohol use in this setting. This study will be the first to utilize biomarkers to overcome challenges in reporting alcohol consumption to determine whether alcohol use is associated with HIV treatment failure in sub-Saharan Africa. This study will generate valuable preliminary data for a larger study of methods to reduce the impact of alcohol on HIV treatment failure.