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. 2025 Aug 8;6(8):100670.
doi: 10.1016/j.medj.2025.100670. Epub 2025 Apr 28.

A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO

Asma Essat  1 , Anaïs Chapel  2 , Kahina Amokrane  3 , Valérie Monceaux  2 , Céline Didier  4 , Adeline Melard  5 , Elise Gardiennet  5 , Véronique Avettand-Fenoel  6 , Sylvie Orr  1 , Faroudy Boufassa  1 , Olivier Lambotte  7 , Michaela Müller-Trutwin  8 , Camille Lécuroux  7 , Antoine Chéret  9 , Cécile Goujard  10 , Christine Rouzioux  11 , Sophie Caillat-Zucman  3 , Laurent Hocqueloux  12 , Daniel Scott-Algara  13 , Laurence Meyer  1 , Asier Sáez-Cirión  14 ; ANRS PRIMO cohort; VISCONTI study
Affiliations

A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO

Asma Essat et al. Med. .

Abstract

Background: There is currently no curative treatment for HIV-1 infection. However, some individuals (defined as posttreatment controllers) durably control viremia after the discontinuation of antiretroviral therapy (ART). Although the ability to achieve this HIV-1 remission status is enhanced by early treatment initiation, the mechanisms leading to posttreatment HIV-1 control remain unclear.

Methods: We retrospectively explored the immunogenetic characteristics of long-term posttreatment controllers from the ANRS VISCONTI study and persons monitored since primary HIV-1 infection in the ANRS PRIMO cohort and evaluated their influence on clinical parameters and outcome after ART discontinuation.

Findings: We identified a major histocompatibility complex (MHC)-related fingerprint favoring sustained HIV-1 remission. HLA-B∗35 alleles, which are associated with rapid progression to AIDS during natural HIV-1 infection, were paradoxically overrepresented among posttreatment controllers and had a positive impact on outcome after treatment discontinuation in people who began therapy during primary infection. Specifically, the influence of HLA-B∗35 alleles was observed when they were carried in combination with other HLA class I alleles expressing Bw4 and C2 ligands of killer immunoglobulin-like receptors (KIRs) in a genetic context that favors KIR education of natural killer (NK) cells (Bw4TTC2 genotype). Accordingly, posttreatment controllers with HLA-B∗35 alleles carry distinct KIR genotypes and NK cells.

Conclusions: The combination of HLA-B∗35 with Bw4TTC2 genotype, associated with KIR education of NK cells, was abundant among posttreatment HIV-1 controllers and promoted viral control after interruption of early-initiated antiretroviral treatment. These results support a role of NK cells in sustained HIV-1 remission.

Funding: The VISCONTI study and the PRIMO cohort are funded by the ANRS-MIE.

Keywords: ART interruption; HIV remission; HIV-1; HLA; HLA-B∗35; KIR; NK cells; Translation to patients; immunogenetics; posttreatment control; primary infection.

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Conflict of interest statement

Declaration of interests The authors declare that they have no competing interests.

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