Research ArticleHIV

Nonprogressing HIV-infected children share fundamental immunological features of nonpathogenic SIV infection

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Science Translational Medicine  28 Sep 2016:
Vol. 8, Issue 358, pp. 358ra125
DOI: 10.1126/scitranslmed.aag1048

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HIV progression at a standstill

Although most people that get infected with HIV develop AIDS, rare individuals maintain immune function in the presence of virus, a phenomenon also seen in natural hosts of the closely related SIV. Muenchhoff et al. describe a cohort of pediatric HIV patients who have normal CD4 T cell counts, despite high viremia and lack of antiviral treatment. These children have low immune activation, including less chemokine receptor CCR5 expression on central memory CD4 T cells, similar to sooty mangabeys infected with SIV. The immune mechanisms described in these patients shed light on HIV pathogenesis, which may help develop future treatments.

Abstract

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.

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