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J Antimicrob Chemother. 2015 Jul;70(7):2108-20. doi: 10.1093/jac/dkv084. Epub 2015 Apr 21.

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

Collaborators (212)

Hoen B, Bourdeaux C, Delfraissy JF, Goujard C, Amri I, Fourn E, Quertainmont Y, Môle M, Rami A, Durel A, Diemer M, Parrinello M, Allègre T, Lafeuillade A, Hittinger G, Lambry V, Carrerre M, Philip G, Duvivier C, Consigny PH, Charlier C, Shoai M, Touam F, Pialoux G, Slama L, L'Yavanc T, Mathurin P, Adda A, Berrebi V, Salmon D, Chakvetadze E, Tassadit T, Ousseima E, Pietri MP, Levy Y, Lascaux AS, Lelievre JD, Giovanna M, Dominguez S, Dumont C, Katlama C, Valentin MA, Seang S, Schneider L, Kiorza N, Chermak A, Ben Abdallah S, Simon A, Pichon F, Pauchard M, Molina JM, Lascoux C, Ponscarme D, Colin De Verdiere N, Scemla A, De Castro N, Rachline A, Garrait V, Rozenbaum W, Ferret S, Balkan S, Clavel F, Tourdjman M, Lafaurie M, Aslan A, Goguel J, Thierry SM, De Lastours V, Gallien S, Pavie J, Delgado J, Mededji C, Veron R, Abel S, Pierre-François S, Baringhton C, Chennebault JM, Vandamme YM, Fialaire P, Rehaiem S, Rabier V, Abgueguen P, Morlat P, Vandenhende MA, Bernard N, Lacoste D, Michaux C, Paccalin F, Receveur MC, Caldato S, Delaune J, Ragnaud JM, Neau D, Lacaze-Buzy L, Livrozet JM, Jeanblanc F, Makhloufi D, Brunel Dalmas F, Jourdain JJ, Chiarello P, Yeni P, Phung B, Rioux C, Godard C, Louni F, El Alami Talbi N, Catalano G, Guiroy F, Reynes J, Jacquet JM, Fauchere V, Merle C, Lemoine V, Loriette M, Morquin D, Makinson A, Atoui N, Tramoni C, Raffi F, Allavena C, Bonnet B, Bouchez S, Feuillebois N, Brunet-François C, Reliquet V, Mounoury O, Morineau-Le-Houssine P, Billaud E, Brosseau D, Hüe H, Dellamonica P, Vassallo M, Leplatois A, Durant J, Naqvi A, Joulié A, Souala F, Michelet C, Arvieux C, Tattevin P, Leroy H, Revest M, Fily F, Chapplain JM, Ratajczak CM, Gras G, Bernard L, Dailloux JF, Laplantine V, Cuzin L, Marchou B, Larrigue S, Chauveau M, Balsarin F, Obadia M, Chéret A, Bonne S, Huleux T, Ajana F, Alcaraz I, Baclet V, Melliez H, Viget N, De La Tribonniere X, Aissi E, Poissy J, Ravaux I, Vallon A, Varan M, May T, Letranchant L, Burty C, Briaud A, Wassoumbou S, Stenzel M, Bouillon MP, Debab Y, Caron F, Gueit I, Chapuzet C, Borsa Lebas F, Etienne M, Miailhes P, Perpoint T, Senechal A, Schlienger I, Cotte L, Augustin Normand C, Boibieux A, Ferry T, Corsini N, Braun E, Lippran J, Biron F, Chidiac C, Pailhes S, Lipman J, Braun E, Koffi J, Thoirain V, Brochier C, Greder Belan A, Therby A, Monnier S, Ruquet M, Garrait V, Richier L, Prevoteau Du Clary F, Philibert P, Chapus C, Cabié A, Abel S.

Author information

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.

KEYWORDS:

HIV DNA; post-treatment controllers; primary HIV infections; reservoirs

PMID:
25900157
DOI:
10.1093/jac/dkv084
[Indexed for MEDLINE]

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