Two critical questions for evaluating cure strategies are: First, how does HIV rapidly escape immune control when antiretroviral therapy (ART) is discontinued, even in patients with decades of viral suppression on treatment? Second, are there changes in immune function that occur very soon after stopping ART that could predict viral relapse before virus is detectable in the blood?
Dr. Steve DeeksA commentary published in the Journal of Clinical Investigation analyzed a study of 29 HIV-positive individuals from Thailand on long-term ART. All stopped treatment—16 as various scheduled attempts at a cure. The investigators found that the innate immune system, which kicks in prior to recognizing a specific viral invader, acts very strongly and very early after stopping ART. The predominant immune cell involved—the plasmacytoid dendritic cell, or pDC—produced large amounts of an interferon known to block viral growth. That activity was noted before HIV was detectable in the blood. Then, for unknown reasons, the pDCs stopped producing large amounts of interferon and HIV became detectable in the blood. The authors of the commentary added that an increase in CD30+ T cells in the blood could also be a harbinger of a failed HIV cure strategy, prior to finding HIV in the blood.
The authors conclude: “Perhaps the most important conceptual advance in this study is that careful interrogation of the immune system just as HIV begins to spread after ART [interruption] can provide unique information regarding why the immune system typically fails to control HIV.” It may also serve as a marker for early return of virus after stopping ART, facilitating evaluation of HIV cure strategies without having to wait for virus to become detectable in the blood.
Commentary co-author Dr. Steve Deeks is affiliated with the amfAR Institute for HIV Cure Research.
Dr. Laurence is amfAR’s senior scientific consultant.