Post-Treatment HIV-1 Controllers with a Long-Term Virological Remission after the Interruption of Early Initiated Antiretroviral Therapy ANRS VISCONTI Study

PLoS Pathogens

Véronique Avettand-Fenoel¹  Benjamin Descours¹  the ANRS VISCONTI Study Group²  Alain Venet³  Brigitte Autran³  Cécile Goujard⁴  Julien Guergnon⁵  Laurent Hocqueloux⁵  Olivier Lambotte⁶  Isabelle Girault⁶  Dominique Costagliola⁷  Camille Lecuroux⁷  Valerie Potard⁷  Laurence Meyer⁸  Christine Rouzioux⁸  Gianfranco Pancino⁸  Adeline Melard⁹  Asier Sáez-Cirión^1,10  Thierry Prazuck^1,10  Pierre Versmisse^1,11  Jean-Paul Viard^1,12  Charline Bacchus^1,12  Faroudy Boufassa^1,12 

[1] AP-HP, CHU Necker-Enfants Malades, Laboratoire de Virologie, Paris, France;AP-HP, Hôpital de Bicêtre, Département d'épidémiologie, Le Kremlin Bicêtre, France;AP-HP, Hôpital de Bicêtre, Service de Médecine Interne, Le Kremlin Bicêtre, France;AP-HP, Hôtel-Dieu, Paris, France;Centre Hospitalier Régional d'Orléans, Service des Maladies Infectieuses et Tropicales, Orléans, France;EA 3620, Université Paris-Descartes, Sorbonne Paris Cité, Paris, France;INSERM U1012, Université Paris-Sud 11, Le Kremlin Bicêtre, France;INSERM U1018, Université Paris-Sud 11, Le Kremlin Bicêtre, France;INSERM, U943, Paris, France;Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France;UPMC Univ Paris 06, UMR_S 943, Paris, France;Université Pierre et Marie Curie, INSERM UMR-S 945 Immunité et Infection, Hôpital Pitié-Salpêtrière, Paris, France

关键词: HIV;    T cells;    HIV-1;    Cytotoxic T cells;    Viral load;    Memory T cells;    T helper cells;    Viremia;   

DOI  :  10.1371/journal.ppat.1003211

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Combination antiretroviral therapy (cART) reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs]) whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs); instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

【 授权许可】

CC BY