In vivo fate of HIV-1-infected T cells: Quantitative analysis of the transition to stable latency

Although it is presumed that the integration of HIV-1 into the genome of infected CD4⁺T lymphocytes allows viral persistence, there has been little direct evidence that CD4⁺T cells with integrated provirus function as a latent reservoir for HIV-1 in infected individuals. Using resting CD4⁺T-cell populations of extremely high purity and a novel assay that selectively and unambiguously detects integrated HIV-1, we show that resting CD4⁺T cells harbouring integrated provirus are present in some infected individuals. However, these cells do not accumulate within the circulating pool of resting CD4⁺T cells in the early stages of HIV-1 infection and do not accumulate even after prolonged periods in long-term survivors of HIV-1 infection. These results suggest that because of viral cytopathic effects and/or host effector mechanisms, productively infected CD4⁺T cells do not generally survive for long enough to revert to a resting memory state in vivo.