Pharmacogenetics of the lipodystrophy syndrome associated with HIV infection and combination antiretroviral therapy

Expert Opin Drug Metab Toxicol. 2011 Nov;7(11):1365-82. doi: 10.1517/17425255.2011.621941.

Abstract

Introduction: Antiretroviral drugs have been associated with several toxicities that limit their success. Of the chronic toxicities, the lipodystrophy syndrome is of special concern due to the metabolic alterations that can accompany it. Why some patients treated with a particular antiretroviral regimen develop lipodystrophy, while others do not, is a medical mystery, but it has been suggested that individuals may (or may not) have a genetically conditioned predisposition. Pharmacogenetics is the science that studies how the genetic composition of individuals can give rise to interindividual variations in response to drugs and drug toxicity.

Areas covered: This article reviews the published investigations on the association between host genetic determinants in treated HIV-infected patients and the presence of lipodystrophy. Studies were identified through a PubMed database search. Case-control and longitudinal studies into pharmacogenetic association were selected. Areas covered include the data on the genetic variants of mitochondrial parameters, cytokines, adipokines, proteins involved in adipocyte biology and proteins involved in stavudine metabolism.

Expert opinion: Most studies provide inconsistent data due to partial genetic evaluation, different assessment of lipodystrophy and low number of patients evaluated. The pharmacogenetics of lipodystrophy in HIV-infected patients treated with antiretroviral drugs still belongs in the research laboratory.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-HIV Agents / adverse effects*
  • Anti-HIV Agents / therapeutic use
  • Antiretroviral Therapy, Highly Active / adverse effects*
  • Drug Therapy, Combination / adverse effects
  • Genetic Predisposition to Disease
  • HIV / drug effects
  • HIV / genetics
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / physiopathology
  • Humans
  • Lipodystrophy / chemically induced*
  • Lipodystrophy / drug therapy
  • Lipodystrophy / genetics*

Substances

  • Anti-HIV Agents