The impact of human genetic variation on HIV disease in the era of HAART

Abstract

Human genetic variation may directly or indirectly influence response to modern antiretroviral therapies for HIV. It is already known that some immunogenetic and other human genetic variations affect the natural history of HIV disease progression where individuals are untreated, but less information is available as to whether these differences are still relevant in the context of HAART. Antiretroviral therapy adds additional opportunities for human genetic contributions to affect variable prognosis--in particular for those genes which influence pharmacokinetics and/or adverse events. To date, the majority of studies investigating the influence of human genetic variation on HIV disease and treatment outcome have focused on single nucleotide polymorphisms or a small number of polymorphisms within a single gene. Reports to date have generally described small effect sizes, and have often been contradictory. Thus, while simple genetic markers relevant to HIV disease or treatment response have indeed been identified (e.g. CCR5delta32 in the context of untreated HIV disease, or HLA-B*5701 allele on the abacavir hypersensitivity reaction in the context of HAART), it is more likely that HIV disease and treatment outcomes are influenced by a multitude of interacting genotypes and phenotypes, a hypothesis that will become increasingly possible to investigate as improvements in molecular and computational technologies are made.