Combined ART started during acute HIV infection protects central memory CD4+ T cells and can induce remission

• Published in: Journal of antimicrobial chemotherapy Vol. 70; no. 7; pp. 2108 - 2120
• Main Authors: Chéret, Antoine, Bacchus-Souffan, Charline, Avettand-Fenoël, Veronique, Mélard, Adeline, Nembot, Georges, Blanc, Catherine, Samri, Assia, Sáez-Cirión, Asier, Hocqueloux, Laurent, Lascoux-Combe, Caroline, Allavena, Clotilde, Goujard, Cécile, Valantin, Marc Antoine, Leplatois, Anne, Meyer, Laurence, Rouzioux, Christine, Autran, Brigitte
• Format: Journal Article
• Language: English
• Published: England Oxford Publishing Limited (England) 01-07-2015; Oxford University Press (OUP)
• Subjects: Adult; Anti-Retroviral Agents - therapeutic use; Antiretroviral drugs; Antiretroviral Therapy, Highly Active - methods; CD4-Positive T-Lymphocytes - immunology; Deoxyribonucleic acid; DNA; Female; HIV; HIV Infections - drug therapy; HIV Infections - immunology; Human immunodeficiency virus; Humans; Immunology; Immunophenotyping; Life Sciences; Male; Memory; Middle Aged; Secondary Prevention - methods; T cell receptors; Treatment Outcome; Young Adult; reservoirs; HIV DNA; post-treatment controllers; primary HIV infections; HIV Infections; Antiretroviral Therapy; Humans; Middle Aged; Immunophenotyping; Male; Treatment Outcome; Anti-Retroviral Agents; Secondary Prevention; Highly Active; Young Adult; Adult; Female; CD4-Positive T-Lymphocytes
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkv084

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.
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).
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.
Early prolonged ART thus limits the size of the HIV reservoir, protects long-lived cells from persistent infection and may enhance post-treatment control.