Antoine Chéret1, Charline Bacchus-Souffan2, Veronique Avettand-Fenoël3, Adeline Mélard3, Georges Nembot4, Catherine Blanc5, Assia Samri2, Asier Sáez-Cirión6, Laurent Hocqueloux7, Caroline Lascoux-Combe8, Clotilde Allavena9, Cécile Goujard10, Marc Antoine Valantin11, Anne Leplatois12, Laurence Meyer4, Christine Rouzioux3, Brigitte Autran2. 1. EA 7327 Paris-Descartes University, Sorbonne Paris-Cité, Virology Laboratory, Necker Enfants-Malades Hospital, Paris, France Infectious Diseases Department, Dron Hospital, Tourcoing, France antoinecheret@free.fr. 2. Pierre & Marie Curie University Paris VI, INSERM UMR-S 945 Immunity & Infection, Pitié-Salpêtrière Hospital, Paris, France. 3. EA 7327 Paris-Descartes University, Sorbonne Paris-Cité, Virology Laboratory, Necker Enfants-Malades Hospital, Paris, France Infectious Diseases Department, Dron Hospital, Tourcoing, France. 4. Epidemiology and Public Health Department, Inserm U1018, AP-HP, Le Kremlin-Bicêtre Hospital, University Paris Sud, Le Kremlin-Bicêtre, France. 5. CyPS Flow Cytometry Platform, Pierre & Marie Curie University, Pitié-Salpêtrière Hospital, Paris, France. 6. Pasteur Institute, Regulation of Retroviral Infections Unit, Paris, France. 7. Infectious Diseases Department, Hospital de la Source, Orléans, France. 8. Infectious Diseases Department, AP-HP, Saint-Louis Hospital, Paris, France. 9. Infectious Diseases Department, Hôtel-Dieu Hospital, Nantes, France. 10. Internal Medicine Department, AP-HP, Le Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France. 11. Infectious Diseases Department, AP-HP, Pitié-Salpêtrière Hospital, University Paris XII, Paris, France. 12. Infectious Diseases Department, l'Archet Hospital, Nice, France.
Abstract
BACKGROUND: Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment. METHODS: We examined the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs). RESULTS: Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and patients treated for 6 years. One patient, who had low reservoir levels in all T cell subsets after 2 years of treatment similar to the levels in PTCs, spontaneously controlled viral replication during 18 months off treatment. CONCLUSIONS: Early prolonged ART thus limits the size of the HIV reservoir, protects long-lived cells from persistent infection and may enhance post-treatment control.
RCT Entities:
BACKGROUND: Therapeutic control of HIV replication reduces the size of the viral reservoir, particularly among central memory CD4+ T cells, and this effect might be accentuated by early treatment. METHODS: We examined the effect of ART initiated at the time of the primary HIV infection (early ART), lasting 2 and 6 years in 11 and 10 patients, respectively, on the HIV reservoir in peripheral resting CD4+ T cells, sorted into naive (TN), central memory (TCM), transitional memory (TTM) and effector memory (TEM) cells, by comparison with 11 post-treatment controllers (PTCs). RESULTS: Between baseline and 2 years, CD4+ T cell subset numbers increased markedly (P < 0.004) and HIV DNA levels decreased in all subsets (P < 0.009). TTM cells represented the majority of reservoir cells at both timepoints, T cell activation status normalized and viral diversity remained stable over time. The HIV reservoir was smaller after 6 years of early ART than after 2 years (P < 0.019), and did not differ between PTCs and patients treated for 6 years. One patient, who had low reservoir levels in all T cell subsets after 2 years of treatment similar to the levels in PTCs, spontaneously controlled viral replication during 18 months off treatment. CONCLUSIONS: Early prolonged ART thus limits the size of the HIV reservoir, protects long-lived cells from persistent infection and may enhance post-treatment control.
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