[Applicability of pharmacogenetic studies in daily clinical practice].
In the last few years, research in pharmacogenetics and pharmacogenomics has identified distinct variants or markers that can help to define the benefits and risk of patients requiring antiretroviral treatment. The beneficial effect of the deletion 32 allele of the CCR5 coreceptor on the natural history of HIV infection and, to a certain extent, on treatment response is well known. The bases of immune reconstitution after initiation of antiretroviral therapy, although the subject of intense study, are probably multifactorial and polygenetic and consequently conclusions with clear applicability to clinical practice are currently lacking. Among the risks, no significant progress has been made in lipodystrophy. The origin of dyslipidemia associated with antiretroviral treatment and the excess cardiovascular risk conferred by some antiretroviral drugs is probably polygenetic and, at present, poorly defined. The genetic bases of efavirenz-induced neurological toxicity and of hyperbilirubinemia secondary to atazanavir are fairly well known, although their application in daily clinical practice has not been adequately assessed. Some aspects that help to understand the molecular bases of hypersensitivity reaction to nevirapine and of nevirapine-induced hepatotoxicity have been described but are not applicable in most cases and consequently further studies are required. Some data correlate tenofovir-induced renal toxicity with genetic variations in some transport proteins. The most significant advance for clinical practice is the correlation between the presence of the HLA-B*5701 allele and hypersensitivity reaction to abacavir. In particular, one clinical trial with a large number of patients from distinct ethnic groups found that the probability of not developing hypersensitivity reaction (immunologically confirmed) was 100% if the patient was HLA-B*5701-negative. These data suggest the need to implement this test in daily clinical practice.
Iribarren Loyarte
José Antonio
JA
Unidad de Enfermedades Infecciosas, Hospital Donostia, San Sebastián, Guipúzcoa, España. JOSEANTONIO.IRIBARRENLOYARTE@osakidetza.net
D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000494:pharmacology*; D020022:Genetic Predisposition to Disease; D015658:HIV Infections / Q000188:drug therapy; D006801:Humans; D010597:Pharmacogenetics
D019380:Anti-HIV Agents