The Impact of Human Genetic Variation on HIV Disease in the Era of HAART

Human genetic variation may directly or indirectly influence response to modern antiretroviral therapies forHIV. It is already known that some immunogenetic and other human genetic variations affect the naturalhistory of HIV disease progression where individuals are untreated, but less information is available as towhether these differences are still relevant in the context of HAART. Antiretroviral therapy adds additionalopportunities for human genetic contributions to affect variable prognosis – in particular for those geneswhich influence pharmacokinetics and/or adverse events. To date, the majority of studies investigating theinfluence of human genetic variation on HIV disease and treatment outcome have focused on single nucleotidepolymorphisms or a small number of polymorphisms within a single gene. Reports to date havegenerally described small effect sizes, and have often been contradictory. Thus, while simple genetic markersrelevant to HIV disease or treatment response have indeed been identified (e.g. CCR5Δ32 in the contextof untreated HIV disease, or HLA-B*5701 allele on the abacavir hypersensitivity reaction in the context ofHAART), it is more likely that HIV disease and treatment outcomes are influenced by a multitude of interactinggenotypes and phenotypes, a hypothesis that will become increasingly possible to investigateas improvements in molecular and computational technologies are made.