{"title":"中断抗逆转录病毒治疗后与持久HIV缓解相关的遗传指纹：ANRS VISCONTI/PRIMO","authors":"Asma Essat, Anaïs Chapel, Kahina Amokrane, Valérie Monceaux, Céline Didier, Adeline Melard, Elise Gardiennet, Véronique Avettand-Fenoel, Sylvie Orr, Faroudy Boufassa, Olivier Lambotte, Michaela Müller-Trutwin, Camille Lécuroux, Antoine Chéret, Cécile Goujard, Christine Rouzioux, Sophie Caillat-Zucman, Laurent Hocqueloux, Daniel Scott-Algara, Laurence Meyer, Asier Sáez-Cirión","doi":"10.1016/j.medj.2025.100670","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Funding: </strong>The VISCONTI study and the PRIMO cohort are funded by the ANRS-MIE.</p>","PeriodicalId":29964,"journal":{"name":"Med","volume":" ","pages":"100670"},"PeriodicalIF":12.8000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO.\",\"authors\":\"Asma Essat, Anaïs Chapel, Kahina Amokrane, Valérie Monceaux, Céline Didier, Adeline Melard, Elise Gardiennet, Véronique Avettand-Fenoel, Sylvie Orr, Faroudy Boufassa, Olivier Lambotte, Michaela Müller-Trutwin, Camille Lécuroux, Antoine Chéret, Cécile Goujard, Christine Rouzioux, Sophie Caillat-Zucman, Laurent Hocqueloux, Daniel Scott-Algara, Laurence Meyer, Asier Sáez-Cirión\",\"doi\":\"10.1016/j.medj.2025.100670\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Findings: </strong>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.</p><p><strong>Conclusions: </strong>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. 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引用次数: 0
摘要
背景：目前还没有治愈HIV-1感染的方法。然而，一些个体（定义为治疗后控制者）在停止抗逆转录病毒治疗（ART）后能持久地控制病毒血症。尽管早期开始治疗可以增强HIV-1缓解状态，但导致治疗后HIV-1控制的机制尚不清楚。方法：我们回顾性地研究了来自ANRS VISCONTI研究的长期治疗后控制者和ANRS PRIMO队列中自原发性HIV-1感染以来监测的人的免疫遗传学特征，并评估了它们对ART停药后临床参数和结局的影响。研究结果：我们确定了一个主要的组织相容性复合体（MHC）相关指纹有利于持续的HIV-1缓解。HLA-B∗35等位基因与自然HIV-1感染期间迅速发展为艾滋病相关，在治疗后控制者中具有矛盾的过度代表性，并且对在原发性感染期间开始治疗的人在停止治疗后的结果具有积极影响。具体来说，当HLA- b * 35等位基因与其他表达杀伤免疫球蛋白样受体（KIRs）的Bw4和C2配体的HLA I类等位基因在有利于自然杀伤（NK）细胞（Bw4TTC2基因型）的KIR教育的遗传背景下结合时，观察到它们的影响。因此，具有HLA-B * 35等位基因的处理后控制者携带不同的KIR基因型和NK细胞。结论：HLA-B∗35与Bw4TTC2基因型结合，与NK细胞的KIR教育相关，在治疗后HIV-1控制者中大量存在，并在早期抗逆转录病毒治疗中断后促进病毒控制。这些结果支持NK细胞在持续的HIV-1缓解中的作用。资助：VISCONTI研究和PRIMO队列由ANRS-MIE资助。
A genetic fingerprint associated with durable HIV remission after interruption of antiretroviral treatment: ANRS VISCONTI/PRIMO.
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.
期刊介绍：
Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically.
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