HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART ^{☆ ☆☆}

Abstract

HIV DNA is a marker of HIV persistence that predicts HIV progression and remission, but its kinetics in early acute HIV infection (AHI) is poorly understood. We longitudinally measured the frequency of peripheral blood mononuclear cells harboring total and integrated HIV DNA in 19 untreated and 71 treated AHI participants, for whom 50 were in the earliest Fiebig I/II (HIV IgM −) stage, that is ≤ 2 weeks from infection. Without antiretroviral therapy (ART), HIV DNA peaked at 2 weeks after enrollment, reaching a set-point 2 weeks later with little change thereafter. There was a marked divergence of HIV DNA values between the untreated and treated groups that occurred within the first 2 weeks of ART and increased with time. ART reduced total HIV DNA levels by 20-fold after 2 weeks and 316-fold after 3 years. Therefore, very early ART offers the opportunity to significantly reduce the frequency of cells harboring HIV DNA.

Highlights

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  The HIV DNA set-point is established early in acute HIV infection.

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  Over three years without antiretroviral therapy, persons with acute HIV infection have total HIV DNA in peripheral blood mononuclear cells that is 300-fold and integrated HIV DNA that is 100-fold higher than those on treatment.

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  Early antiretroviral therapy provides an opportunity to markedly reduce proviral HIV DNA burden,

HIV is difficult to cure because it infects long-lived cells in the body, also called “reservoirs”. Having a small HIV reservoir size may benefit health. We show that HIV DNA in peripheral blood cells, a marker of the HIV reservoir size, establishes a set-point level during the first 6 weeks of infection and changes little over time without HIV medications. However, if HIV medications are started early, the reservoir size declines rapidly, and is 300-fold lower than that seen in untreated persons. Currently the most effective way to significantly lower the HIV reservoir size is with very early treatment.