Brief Report: Toll-like Receptor 9-1635A/G Polymorphism Is Associated With HIV-1 Rebound After Four Weeks of Interruption of Antiretroviral Therapy

Abstract

Objectives:This study aims to analyze the association of the presence of common polymorphisms [single nucleotide polymorphisms (SNPs)] on Toll-like receptors (TLRs), such as TLR9-1635A/G, TLR2-1892A/C, TLR2-2258G/A, TLR4-899A/G, and TLR4-1196C/T, with the viral rebound after stopping antiretroviral treatment (ART). CCR5-Δ32 deletion and HLA-A/HLA-B alleles were also analyzed.Design:Interruption of ART may be required to investigate the outcome of strategies aimed to achieve drug-free HIV remission or cure. However, interruption of ART is currently not indicated. This was a retrospective longitudinal study that included 57 long-term suppressed HIV-1-infected individuals.Methods:TLR SNPs were detected by real-time polymerase chain reaction (PCR). CCR5-Δ32 was analyzed by conventional PCR and HLA-A and HLA-B alleles by PCR-SSOP Luminex.Results:HIV-1 RNA rebound at week 4 after treatment interruption positively correlated with pre-ART HIV-1 load (P = 0.025). The TLR9-1635AA genotype was independently associated with a higher HIV-1 rebound compared with those with AG + GG genotype (multivariate stepwise regression analysis, P = 0.004). Women had lower HIV-1 RNA load both at rebound and during the 72 weeks of follow-up compared with men (P < 0.05 at all time-points), whereas CD4 nadir and CD4 count set-point were similar according to sex. The pre-ART viral load was independently associated with the viral set-point (P = 0.001), whereas the presence of the HLA-A01 allele (P = 0.027) and the CD4 nadir (P = 0.001) were associated with the CD4 count set-point.Conclusions:The association of the TLR9-1635AA genotype with a higher HIV-1 rebound suggests that this SNP may affect the results from strategies requiring interruption of ART aimed to cure HIV-1 infection.