Pharmacogenomics of antiretroviral therapy in Latin America

Abstract

AIDS is caused by infection with human immunodeficiency virus (HIV), which when untreated produces a critical decline in CD4+ T cells, triggering a progressive dysfunction of the immune system and the development of opportunistic infections and/or malignancies leading to death. Currently, there are more than 20 anti-retrovirals (ARVs) approved for commercial use in Latin America, and a large number of new ARV studies. These are divided into 6 classses: Nucleos(t)ide analogue reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PI), fusion inhibitors (FIs), co-receptor antagonists (CCR5-antagonists) and integrase inhibitors (INSTI). Nevertheless, the high inter-individual variability in the response and the adverse effects of these drugs has been the main explanation for the lack of adherence to treatment. In Latin America several studies have been conducted to evaluate the frequency of the polymorphisms in proteins related to pharmacotherapeutic response to ARV treatment both in patients living with HIV and/or in the general population. The results show variable frequencies between the different countries, regions and/or ethnicities. Despite international evidence on the importance of these polymorphisms to the success of ARV therapy, findings are controversial, since most of the studies conducted are focused only on one genetic variant and just a single drug, without addressing the complexity of multidrug treatment currently used in patients, and particularly in patients from multi-ethnic backgrounds.