In July of 2012, Timothy Henrich from Brigham and Women's Hospital in Massachusetts first reported on two HIV-positive individuals in the Boston area who had undergone stem cell transplants to treat cancers, and subsequently lost all detectable traces of virus reservoirs. These case reports were later published in the Journal of Infectious Diseases. Both individuals were maintained on antiretroviral therapy (ART) throughout the transplantation procedures and afterward, so initially it was uncertain if the results represented a profound depletion of HIV reservoir levels or a cure of the infection. Earlier this year Henrich presented short-term results after ART interruptions, drawing widespread attention because HIV levels remained undetectable (for seven and 15 weeks of follow up, respectively), prompting hope that a cure may have been achieved. But yesterday at a scientific conference in Miami, Henrich shared the disappointing news that HIV viral load has since rebounded to detectable levels in both individuals, leading to the restarting of ART—in one case in August, 12 weeks after the ART interruption, and in the other in November, after 32 weeks off treatment. Both remain in good health.
The first response to these findings is to feel for the two individuals involved. In the scientific context of the search for an HIV cure, the outcomes are sobering but also have the potential to make a massive contribution to the research effort. One immediate implication is that the use of stem cells from a donor lacking the CCR5 co-receptor may have been crucial to the case of Timothy Brown, who for now is the lone adult considered cured of HIV (he remains off ART with no viral rebound for over six years and counting). Henrich’s patients received stem cell transplants from donors with normal levels of CCR5, and there was speculation that perhaps other elements of the procedure could contribute to eliminating HIV (such as the immune-depleting conditioning regimens that are used, and/or the transient graft-versus-host disease that developed afterward). The results also emphasize that a short-term absence of HIV rebound after stopping ART must be viewed cautiously and cannot be interpreted as evidence of a cure (Henrich was careful to stress this point when he described the initial lack of rebound earlier this year), and highlight the challenge of identifying trace amounts of HIV in the body that can fly beneath the radar of current technologies. Further discussion of the cases and their implications for cure research can be expected at the Conference on Retroviruses and Opportunistic Infections (CROI), which takes place in Boston from March 3-6, 2014.