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

被引:90
作者
Cheret, Antoine [1 ,2 ]
Bacchus-Souffan, Charline [3 ]
Avettand-Fenoel, Veronique [1 ,2 ]
Melard, Adeline [1 ,2 ]
Nembot, Georges [4 ]
Blanc, Catherine [5 ]
Samri, Assia
Saez-Cirion, Asier [6 ]
Hocqueloux, Laurent [7 ]
Lascoux-Combe, Caroline [8 ]
Allavena, Clotilde [9 ]
Goujard, Cecile [10 ]
Valantin, Marc Antoine [11 ]
Leplatois, Anne [12 ]
Meyer, Laurence [4 ]
Rouzioux, Christine [1 ,2 ]
Autran, Brigitte [3 ]
机构
[1] Univ Paris 05, Hop Necker Enfants Malad, Sorbonne Paris Cite, Virol Lab,EA 7327, F-75015 Paris, France
[2] Dron Hosp, Dept Infect Dis, Tourcoing, France
[3] Univ Paris 06, Pitie Salpetriere Hosp, INSERM UMR S Immun & Infect 945, Paris, France
[4] Univ Paris Sud, Le Kremlin Bicetre Hosp, AP HP, Inserm U1018,Epidemiol & Publ Hlth Dept, F-94275 Le Kremlin Bicetre, France
[5] Univ Paris 06, Pitie Salpetriere Hosp, CyPS Flow Cytometry Platform, Paris, France
[6] Inst Pasteur, Regulat Retroviral Infect Unit, Paris, France
[7] Hosp Source, Orleans, France
[8] St Louis Hosp, AP HP, Dept Infect Dis, Paris, France
[9] Hop Hotel Dieu, Dept Infect Dis, Nantes, France
[10] Le Kremlin Bicetre Hosp, AP HP, Dept Internal Med, Le Kremlin Bicetre, France
[11] Univ Paris 12, Pitie Salpetriere Hosp, AP HP, Dept Infect Dis, Paris, France
[12] LArchet Hosp, Dept Infect Dis, Nice, France
关键词
primary HIV infections; post-treatment controllers; HIV DNA; reservoirs; CD4(+) T-CELLS; RECEIVING ANTIRETROVIRAL THERAPY; GASTROINTESTINAL-TRACT; DNA; RESERVOIR; BLOOD; INITIATION; TIME; ESTABLISHMENT; REPLICATION;
D O I
10.1093/jac/dkv084
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
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.
引用
收藏
页码:2108 / 2120
页数:13
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