Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir

Chun T-W et al. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: Implications for eradication. AIDS 2010 Oct 19.

The persistence of HIV in CD4 cells despite full virologic suppression in plasma renders the prospect of viral eradication highly unlikely, at least with present strategies. However, initiation of antiretroviral therapy (ART) very early during acute HIV infection limits the size of the viral reservoir, and some studies suggest that it may deplete the pool of HIV-infected CD4 cells over time. In this study, researchers further explore whether early, long-term administration of potent ART might eliminate viral reservoirs.

Using quantitative real-time polymerase chain reaction, the researchers measured genomic HIV DNA in highly purified CD4 cells obtained from 44 patients who had achieved long-term suppression on ART without any episodes of detectable viremia.

Nine of the patients had started ART <6 months after acquiring HIV. These patients were found to have significantly lower levels of HIV proviral DNA (mean, 4.6 copies per million CD4 cells) than the patients who started ART later, and four of them had no proviral DNA detected.

One such patient was found to have an extremely low level of virus after 10.5 years of ART (1 infected cell per 1.7 billion CD4 cells). Under close follow-up, this patient discontinued ART. For 7 weeks, he had no virus detected in his plasma, but then his plasma HIV RNA level rebounded to 1593 copies/mL.

It spontaneously returned to an undetectable level for a brief period, only to rebound again during week 20, reaching 8684 copies/mL. At that time, ART was restarted.

Comment:

In this study and others, initiating long-term effective ART very early rather than later was associated with lower levels of residual HIV. Nonetheless, this seemingly favorable combination of very early ART, long-term consistent virologic suppression, and a very limited viral burden in the reservoir of CD4 cells did not prevent HIV recurrence after withdrawal of ART.

Although reemergence of the virus took longer in the patient described here than in patients in other studies who had less favorable circumstances, viral rebound still occurred in <2 months. Long-term virologic suppression without ART will require novel strategies to target the rare infected cells that rekindle the infection systemically.