Antiretroviral therapy and genetic predisposition: Cofactors contributing to the lipodystrophy syndrome

The TNF-α-238G/A single nucleotide polymorphism (SNP) independently increases the risk of lipodystrophy progression. The current study evaluates the contribution of the different antiretroviral treatments (ART) regimens administered to HIV infected individuals in Pune to the development of lipodystrophy and insulin resistance in patients having TNF-α-238G/A polymorphism. A total of 172 HIV-1 infected patients were enrolled in the study and were subdivided into patients with [HIV+LIPODYS+ (cases)] and without lipodystrophy [HIV+LIPODYS- (controls)]. We assessed the contribution of the typical 2NRTI+1 NNRTI based ART regimens prescribed in our clinics with the development of dyslipidemia and insulin resistance in both the above study group. A significantly higher percentage of patients with lipodystrophy expressed the TNF-α-238G/A polymorphism. Significant correlations were observed between Adiponectin, TNF-α protein levels and type of ART-ART regimen. Our results showed that the NNRTI efavirenz contributed more to the lipodystrophy syndrome as compared to other antiretroviral drugs tested. The TNF-α 238G/A SNP contributes to changes in insulin sensitivity and lipodystrophy.   Key words: HIV-1, antiretroviral drugs, single nucleotide polymorphism, lipodystrophy, dyslipidemia, adiponectin, insulin resistance, metabolic syndrome.