Infrequent recovery of HIV from but robust exogenous infection of activated CD4+ T Cells in HIV Elite Controllers

Abstract

Background. Human immunodeficiency virus (HIV) elite controllers are able to control infection with HIV- 1 spontaneously to undetectable levels in the absence of antiretroviral therapy, but the mechanisms leading to this phenotype are poorly understood. Although low frequencies of HIV-infected peripheral CD4+ T cells have been reported in this group, it remains unclear to what extent these are due to viral attenuation, active immune containment, or intracellular host factors that restrict virus replication. Methods. We assessed proviral DNA levels, autologous viral growth from and infectability of in vitro activated, CD8+ T cell-depleted CD4+ T cells from HIV elite controllers (mean viral load, <50 copies/mL), viremic controllers (mean viral load, <2000 copies/mL), chronic progressors, and individuals receiving highly active antiretroviral therapy. Results. Although we successfully detected autologous virus production in ex vivo activated CD4+ T cells from all chronic progressors and from most of the viremic controllers, we were able to measure robust autologous viral replication in only 2 of 14 elite controllers subjected to the same protocol. In vitro activated autologous CD4+ T cells from elite controllers, however, supported infection with both X4 and R5 tropic HIV strains at comparable levels to those in CD4 + T cells from HIV-uninfected subjects. Proviral DNA levels were the lowest in elite controllers, suggesting that extremely low frequencies of infected cells contribute to difficulty in isolation of virus. Conclusions. These data indicate that elite control is not due to inability of activated CD4+ T cells to support HIV infection, but the relative contributions of host and viral factors that account for maintenance of low-level infection remain to be determined. © 2010 by the Infectious Diseases Society of America. All rights reserved.