Combined ART started during acute HIV infection protects central memory CD4+ T cells and can induce remission
Author:
Chéret Antoine12, Bacchus-Souffan Charline3, Avettand-Fenoël Veronique12, Mélard Adeline12, Nembot Georges4, Blanc Catherine5, Samri Assia3, Sáez-Cirión Asier6, Hocqueloux Laurent7, Lascoux-Combe Caroline8, Allavena Clotilde9, Goujard Cécile10, Valantin Marc Antoine11, Leplatois Anne12, Meyer Laurence4, Rouzioux Christine12, Autran Brigitte3, Hoen B., Bourdeaux C., Delfraissy J. F., 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 P. H., 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 M. P., Levy Y., Lascaux A. S., Lelievre J. D., Giovanna M., Dominguez S., Dumont C., Katlama C., Valentin M. A., Seang S., Schneider L., Kiorza N., Chermak A., Ben Abdallah S., Simon A., Pichon F., Pauchard M., Molina J. M., 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 S. M., De Lastours V., Gallien S., Pavie J., Delgado J., Mededji C., Veron R., Abel S., Pierre-François S., Baringhton C., Chennebault J. M., Vandamme Y. M., Fialaire P., Rehaiem S., Rabier V., Abgueguen P., Morlat P., Vandenhende M. A., Bernard N., Lacoste D., Michaux C., Paccalin F., Receveur M. C., Caldato S., Delaune J., Ragnaud J. M., Neau D., Lacaze-Buzy L., Livrozet J. M., Jeanblanc F., Makhloufi D., Brunel Dalmas F., Jourdain J. J., Chiarello P., Yeni P., Phung B., Rioux C., Godard C., Louni F., El Alami Talbi N., Catalano G., Guiroy F., Reynes J., Jacquet J. M., 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 J. M., Ratajczak C. M., Gras G., Bernard L., Dailloux J. F., 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 M. P., 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.,
Affiliation:
1. 1 EA 7327 Paris-Descartes University, Sorbonne Paris-Cité, Virology Laboratory, Necker Enfants-Malades Hospital, Paris, France 2. 2 Infectious Diseases Department, Dron Hospital, Tourcoing, France 3. 3 Pierre & Marie Curie University Paris VI, INSERM UMR-S 945 Immunity & Infection, Pitié-Salpêtrière Hospital, Paris, France 4. 4 Epidemiology and Public Health Department, Inserm U1018, AP-HP, Le Kremlin-Bicêtre Hospital, University Paris Sud, Le Kremlin-Bicêtre, France 5. 5 CyPS Flow Cytometry Platform, Pierre & Marie Curie University, Pitié-Salpêtrière Hospital, Paris, France 6. 6 Pasteur Institute, Regulation of Retroviral Infections Unit, Paris, France 7. 7 Infectious Diseases Department, Hospital de la Source, Orléans, France 8. 8 Infectious Diseases Department, AP-HP, Saint-Louis Hospital, Paris, France 9. 9 Infectious Diseases Department, Hôtel-Dieu Hospital, Nantes, France 10. 10 Internal Medicine Department, AP-HP, Le Kremlin-Bicêtre Hospital, Le Kremlin-Bicêtre, France 11. 11 Infectious Diseases Department, AP-HP, Pitié-Salpêtrière Hospital, University Paris XII, Paris, France 12. 12 Infectious Diseases Department, l'Archet Hospital, Nice, France
Abstract
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.
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology,Microbiology (medical)
Cited by
83 articles.
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