Background: Some HIV-1 infected individuals durably control viremia after interruption of early ART (post-treatment controllers, PTC). The mechanisms associated with this phenomenon are unclear. Prevalence of HLA-B*35, associated with rapid progression without therapy, is high among PTC in the VISCONTI study. In contrast, HLA-B*27/57 alleles, associated with HIV-control, are not overrepresented in PTC. We investigated the association between HLA-B*35 and HIV remission.
Methods: CD4+ T-cell counts, plasma viral loads, PBMC-associated HIV-DNA levels were analysed in 245 HLA-typed HIV-infected individuals from the ANRS PRIMO cohort, on ART for at least 12 months since primary infection. HLA and KIR genotyping and NK cell analyses were done in PTC (n=10) from the ANRS VISCONTI study. Results were compared to HIV-infected (viremic, on cART, HIV-controllers) and non-infected individuals.
Results: In the PRIMO cohort, despite similar time since infection, HLA-B*35 individuals (B35, n=64) had lower CD4+ T-cell counts (median 398 cells/mm3, p=0.04) and higher HIV-DNA level (median 3.53 log10 HIV-DNA copies/million PBMC, p=0.046) than HLA-B*27/57 (B27/57, n=21, 543 cells/mm3 and 2.88 log10 HIV-DNA copies) individuals or those carrying other HLAs (others, n=160, 481 cells/mm3 and 3.44 log10 HIV-DNA copies) at the time of treatment initiation. After a similar period on ART (~5 years) the only difference was B27/57 having lower HIV-DNA levels (median < 1.7 log10 vs 2.5 and 2.3 for B35 and others, p=0.01). Among those interrupting the treatment, B35 were more likely to maintain viral control than B27/57 or others (p=0.01). B35 who controlled HIV carried more frequently KIR ligands Bw4 or C2/C2 (f=0.8, p=0.04) than B35 not controllers (f=0.39). In the VISCONTI study, PTC also carried often the Bw4 epitope (f=0.85 vs 0.44 in non-infected controls, p=0.02) and had high prevalence of the KIR B haplotype (f=0.86 vs 0.4). Phenotypical differences and increased anti-HIV activity of NK cells were observed in PTC compared to other HIV-infected individuals (p=0.01).
Conclusions: Our results suggest that HLA-B*35 might favour post-treatment control, despite unfavourable primary HIV-infection, in some early treated individuals. This might be associated with the presence of KIR Bw4 and C2 ligands in the MHC of PTC, enrichment of KIR B genotype and optimal licensing of NK cells.