The influence of HLA supertype on thymidine analogue associated with low peripheral fat in HIV

Objectives: To examine the relationship between human leukocyte antigen (HLA) genotype and body composition changes induced by thymidine analogue nucleoside reverse transcriptase inhibitor (NtRTI) use in HIV-positive individuals. Design: Data collected during the Simplification with Tenofovir-Emtricitabine (TDF-FTC) or Abacavir-Lamivudine (ABC-3TC) (STEAL) study were analysed to examine the potential association of HLA genotypes with changes in body composition in treatment-experienced HIV-positive individuals. Methods: Demographic, HIV-related, body composition and HLA genotyping data from the STEAL study were used in this analysis. The mean percentage peripheral fat at study baseline was compared in participants with and without prior NtRTI use. Analyses were also carried out for each HLA supertype strata, for five HLA genes, within the thymidine-exposed group. These comparisons were made using Mann-Whitney rank-sum tests. Results: Participants with prior NtRTI use had a significantly lower baseline mean peripheral fat percentage compared to those without NtRTI use (31.9 vs. 34.7%; P = 0.0045). However, participants carrying one or more of the three particular HLA supertype alleles, A01, B08 and DQ2, showed no significant difference in mean peripheral fat percentage at baseline by NtRTI use. Among participants with prior NtRTI exposure, there were significant differences in mean peripheral fat by HLA A01, B08 and DQ2 allele expression compared to those without expression of these alleles (A01: 34.91% vs. no A01: 30.3%; P = 0.0087; B08: 36.2% vs. no B08: 31.1%; P = 0.0317; DQ2: 35.16% vs. no DQ2: 30.06%; P = 0.0081). Conclusion: This analysis suggests that HIV-infected individuals carrying HLA A01, B08 or DQ2 supertype alleles may be resistant to NtRTI-induced peripheral fat loss.