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Title
Association between immunogenetic factors and post-treatment control of HIV-1 infection. ANRS VISCONTI and PRIMO studies
Presenter
Asier Sáez-Cirión
Authors
A. Essat1, D. Scott-Algara2, V. Monceaux3, V. Avettand-Fenoel4,5, C. Didier2, S. Caillat-Zucman6, S. Orr1, I. Theodorou6,7, C. Goujard1,8, F. Boufassa1, O. Lambotte8,9, C. Rouzioux4,5, L. Hocqueloux10, L. Meyer1,8, A. Sáez-Cirión3, ANRS PRIMO and VISCONTI studies
Institutions
1INSERM CESP U1018, University Paris Sud, Le Kremlin Bicêtre, France, 2Institut Pasteur, Unité régulation des infections rétrovirales, Paris, France, 3Institut Pasteur, Unité HIV inflammation et persistance, Paris, France, 4Université Paris Descartes, Sorbonne Paris Cité, EA7327, Paris, France, 5AP-HP, Laboratoire de Virologie, CHU Necker-Enfants Malades, Paris, France, 6Laboratoire d'Immunologie et Histocompatibilité Hôpital St. Louis, Paris, France, 7UPMC UMRS CR7 - Inserm U1135 - CNRS ERL 8255, Paris, France, 8APHP, Bicêtre Hospital, Univ Paris-Sud, Le Kremlin Bicêtre, France, 9ImVA UMR 1184, Le Kremlin Bicêtre, France, 10CHR d'Orléans - La Source, Service des Maladies Infectieuses, Orléans, France

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.