XIX International AIDS Conference

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THPE003 - Poster Exhibition


Approaching an elite controller status through early initiation of antiretroviral therapy

M.J. Buzon1,2, P. McLaren3, K. Seiss1, N. Zangger3, A. Stone1, F. Pareyra1,4, E. Rosenberg2, A. Telenti3, X. Yu1, M. Lichterfeld2

1Massachusetts General Hospital, Ragon Institute of MGH, MIT and Harvard, Cambridge, United States, 2Infectious Disease Division, Massachusetts General Hospital, Boston, United States, 3Swiss Institute of Bioinformatics, Lausanne, Switzerland, 4Infectious Disease Division, Brigham and Women's Hospital, Boston, United States

Background: Recent studies showed that prolonged treatment with HAART initiated during acute infection allowed for subsequent drug-free control of HIV-1 infection in approximately 20% of persons (Hocqueloux et al, AIDS 2010), suggesting that at least in some patients, early HIV-1 therapy may induce a “functional cure” of HIV-1 infection that mimics spontaneous viral control observed in elite controllers. Here, we investigated characteristics of a unique cohort of patients who started treatment early during infection and remained on fully suppressive HAART for >10 years.
Methods: 37 Elite Controllers (EC), 10 chronic treated (CT) patients and 8 early treated (ET) patients who initiated ART within 90 days of seroconversion were included; all of these patients had undetectable viremia for >10 years. HIV-1-specific T cells were determined by interferon-g elispots. Levels of total, integrated and 2-LTR HIV-1 DNA were measured by qPCR in bulk CD4 T cells. The presence of replication-competent virus was evaluated using functional reactivation assays. mRNA and miRNA gene expression signatures were analyzed using microarray-based assays or digital gene expression analysis using Nanostring technology, respectively.
Results: Individuals treated during early infection had significantly lower levels of HIV-1-specific T and B cell responses, as compared to the two reference groups. Levels of integrated, total HIV-1 DNA and 2-LTR circles Gene set enrichment analysis of transcriptional signatures indicated that gene expression patterns from ET and EC were more similar to each other than to CT. In addition, miRNA expression profiles in ET were distinct from those of CT, while more closely resembling corresponding patterns from EC. Finally, efficiency of viral reactivation was comparable in EC and ET, while significantly more replication-competent virus was retrieved from CT.
Conclusions: Prolonged therapy with HAART initiated early during acute infection induces an HIV-1 disease status that in many aspects is reminiscent of the elite controller phenotype.


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