<jats:sec><jats:title>Objectives</jats:title><jats:p>Adiponectin is a circulating peptide secreted by mature adipocytes that may act as a regulator of glucose and lipid metabolism. This study aimed to investigate the association between genetic variability in the adiponectin receptor genes <jats:styled-content style="fixed-case"><jats:italic>ADIPOR1</jats:italic></jats:styled-content> (adiponectin receptor 1) and <jats:styled-content style="fixed-case"><jats:italic>ADIPOR2</jats:italic></jats:styled-content> and lipodystrophy and its related anthropometric and metabolic phenotypes in <jats:styled-content style="fixed-case">HIV</jats:styled-content>‐infected patients on highly active antiretroviral therapy (<jats:styled-content style="fixed-case">HAART</jats:styled-content>).</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>We studied six single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNPs</jats:styled-content>) in the adiponectin receptor genes <jats:styled-content style="fixed-case"><jats:italic>ADIPOR1</jats:italic></jats:styled-content> (rs1342387 and rs10920533) and <jats:styled-content style="fixed-case"><jats:italic>ADIPOR2</jats:italic></jats:styled-content> (rs11061925, rs10773983, rs929434 and rs767870) and their association with adiponectin plasma levels, lipodystrophy subtypes and other parameters linked to glucose and lipid metabolism involved in the lipodystrophic syndrome. The genotypes of 407 <jats:styled-content style="fixed-case">HIV</jats:styled-content>‐infected patients receiving <jats:styled-content style="fixed-case">HAART</jats:styled-content> were investigated using real‐time polymerase chain reaction. Mean biochemical and anthropometrical parameters were compared between the different genotypes using analysis of variance.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Two <jats:styled-content style="fixed-case"><jats:italic>ADIPOR2</jats:italic> SNPs</jats:styled-content> (rs11061925 and rs929434) were associated with fasting plasma triglyceride concentrations in the entire sample. Stronger significant associations were found between these <jats:styled-content style="fixed-case">SNPs</jats:styled-content> and biochemical parameters (levels of triglycerides, total cholesterol, adiponectin and glucose) in men. We did not find any significant associations with <jats:styled-content style="fixed-case"><jats:italic>ADIPOR1</jats:italic></jats:styled-content> gene variants.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:styled-content style="fixed-case">SNPs</jats:styled-content> in the <jats:styled-content style="fixed-case"><jats:italic>ADIPOR2</jats:italic></jats:styled-content> gene appear to be involved in the metabolic alterations in <jats:styled-content style="fixed-case">HIV</jats:styled-content>‐infected men receiving <jats:styled-content style="fixed-case">HAART</jats:styled-content>.</jats:p></jats:sec>