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Friday, July 27, 2012

Starting HIV Medications Within 10 Weeks from Infection Can Create Elite Controllers After 3 Years of Treatment

Distribution of the HIV reservoir in patients spontaneously controlling HIV infection after treatment interruption

Presented by Charline Bacchus (France).

C. Bacchus1, L. Hocqueloux2, V. Avettand-Fenoël3, A. Saez-Cirion4, A. Mélard3, B. Descours5, A. Samri1, C. Blanc6, B. Autran1, C. Rouzioux3, VISCONTI and ALT ANRS study groups

1Cellular and Tissular Immunology Laboratory, Pierre and Marie Curie University, INSERM UMR-S 945, Pitié-Salpêtrière Hospital, Paris, France, 2Infectious and Tropical Diseases Department, Regional Hospital, Orléans, France, 3Virology Laboratory, René Descartes University, Necker Hospital, Paris, France,4Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France, 5Human Genetic Institute, Molecular Virology Laboratory, CNRS UPR1142, Montpellier, France, 6Flow Cytometry Platform CyPS, Pierre and Marie Curie University, Pitié-Salpêtrière Hospital, Paris, France

Background: Virological and Immunological Studies in CONtrollers after Treatment Interruption (VISCONTI) are required to understand the benefits of an early treatment at acute HIV-1 infection on the HIV reservoir. We studied the distribution, magnitude and inducibility of the HIV reservoir in VISCONTI patients.
Methods: The prospective VISCONTI study included twelve patients controlling HIV for a median of 76[IQR:67.5-84.5] months after interruption of a 3[IQR:1.7-5.9] years long HAART initiated within 10 weeks post-infection. Circulating resting CD25-CD69-HLADR- CD4+T cell subsets were sorted as naive (TN), central-memory (TCM), transitional-memory (TTM) and effector-memory cells (TEM) for further cell-associated HIV-DNA quantification by ultrasensitive real-time-PCR, and viral inducibility by culture with anti-CD3/anti-CD28/IL-2/IL-7. Reservoir distribution was compared to the one observed in 8 untreated Elite-Controllers for whom 90% of HIV-RNA measures was undetectable (below 200 copies) over 12[9-14] years.
Results: In the VISCONTI group, activated CD4+T cells had significantly higher HIV-DNA levels than resting ones (median 2.7[IQR:2.4-3.4] and 2[IQR:1.8-2.5] log copies/million cells, p=0.005). HIV-DNA was detected in all subsets from all patients except for 8 out of 12 TN-sorted cells, which were 10 fold less infected than all memory subsets (median TN:1.5[IQR:1.2-1.6], TCM:2.5[IQR:1.8-2.9], TTM:2.6[IQR:2.2-2.8] and TEM:2.4[IQR:2-2.8] log copies/million cells, p< 0.007). TTM was the major subset contributing to 56% of this reservoir. The same HIV reservoir characteristics were observed in Elite-Controllers in term of magnitude and distribution, except that both TCM and TTM equally contributed to the Elite-Controllers HIV reservoir. The VISCONTI HIV reservoir was inducible after TCR-stimulation in all sorted memory subsets from all patients, except in TN where no virus was recovered in 6 out of 8 patients.
Conclusions: In VISCONTI patients, treatment initiated at primary HIV-1 infection leads, after treatment interruption, to a low -but inducible- durable HIV reservoir distributed mainly in short-lived memory CD4+T cells that mimicks the natural distribution observed in Elite-Controllers.

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