Research ArticleHIV

Abundant HIV-infected cells in blood and tissues are rapidly cleared upon ART initiation during acute HIV infection

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Science Translational Medicine  04 Mar 2020:
Vol. 12, Issue 533, eaav3491
DOI: 10.1126/scitranslmed.aav3491

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Clearing a path for an HIV cure

Curing HIV is more feasible if we better understand the formation of the latent viral reservoir. Leyre et al. studied longitudinal blood and tissue samples during acute HIV infection. The large pool of infected cells present at early stages did not survive antiretroviral treatment. Infected cells at later stages were more prevalent in lymphoid tissues than in blood. These results show that most infected targets are cleared with early treatment, but HIV+ cells that remain after a certain stage are more likely to persist. These persistent cells are the ones that will need to be eradicated for a cure to be achieved.

Abstract

The timing and location of the establishment of the viral reservoir during acute HIV infection remain unclear. Using longitudinal blood and tissue samples obtained from HIV-infected individuals at the earliest stage of infection, we demonstrate that frequencies of infected cells reach maximal values in gut-associated lymphoid tissue and lymph nodes as early as Fiebig stage II, before seroconversion. Both tissues displayed higher frequencies of infected cells than blood until Fiebig stage III, after which infected cells were equally distributed in all compartments examined. Initiation of antiretroviral therapy (ART) at Fiebig stages I to III led to a profound decrease in the frequency of infected cells to nearly undetectable level in all compartments. The rare infected cells that persisted were preferentially found in the lymphoid tissues. Initiation of ART at later stages (Fiebig stages IV/V and chronic infection) induced only a modest reduction in the frequency of infected cells. Quantification of HIV DNA in memory CD4+ T cell subsets confirmed the unstable nature of most of the infected cells at Fiebig stages I to III and the emergence of persistently infected cells during the transition to Fiebig stage IV. Our results indicate that although a large pool of cells is infected during acute HIV infection, most of these early targets are rapidly cleared upon ART initiation. Therefore, infected cells present after peak viremia have a greater ability to persist.

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