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Disease-free infection in HIV-infected adults is associated with human leukocyte antigen-mediated suppression of viremia, whereas in the sooty mangabey and other healthy natural hosts of simian immunodeficiency virus (SIV), viral replication continues unabated. To better understand factors preventing HIV disease, we investigated pediatric infection, where AIDS typically develops more rapidly than in adults. Among 170 nonprogressing antiretroviral therapy-naïve children aged >5 years maintaining normal-for-age CD4 T cell counts, immune activation levels were low despite high viremia (median, 26,000 copies/ml). Potent, broadly neutralizing antibody responses in most of the subjects and strong virus-specific T cell activity were present but did not drive pediatric nonprogression. However, reduced CCR5 expression and low HIV infection in long-lived central memory CD4 T cells were observed in pediatric nonprogressors. These children therefore express two cardinal immunological features of nonpathogenic SIV infection in sooty mangabeys-low immune activation despite high viremia and low CCR5 expression on long-lived central memory CD4 T cells-suggesting closer similarities with nonpathogenetic mechanisms evolved over thousands of years in natural SIV hosts than those operating in HIV-infected adults.

Original publication

DOI

10.1126/scitranslmed.aag1048

Type

Journal article

Journal

Science translational medicine

Publication Date

09/2016

Volume

8

Pages

358ra125 - 358ra125

Addresses

Department of Paediatrics, Peter Medawar Building for Pathogen Research, South Parks Road, University of Oxford, Oxford OX1 3SY, U.K. HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu-Natal (UKZN), Durban, South Africa. Max von Pettenkofer-Institute, Department of Virology, Ludwig-Maximilians-University Munich, Munich, Germany. German Center for Infection Research (DZIF), Partner Site Munich, Germany.