HIV rebounds in Boston stem cell transplant recipients

1 February 2014. Related: Cure-related research, Basic science and immunology.

Richard Jefferys, TAG

On 5th December 213, at a scientific conference in Miami, Timothy Henrich from Brigham and Women’s Hospital in Massachusetts, shared the disappointing news that HIV viral load had rebounded to detectable levels in two individuals who had previously undergone stem cell transplantation and later discontinued HIV treatment. [1]

This lead to restarting of antiretroviral therapy (ART)—in one case in August of this year, in the other more recently after eight months off treatment.

In July 2012, Henrich 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. [2] These case reports were later published in the Journal of Infectious Diseases. [3]

Both individuals were maintained on ART throughout the transplantation procedures and afterwards, 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. [4]

The first response to these findings is concern 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 emphasise 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 3-6 March, 2014. [5]

Source:

TAG Basic Science Blog. HIV rebounds in Boston stem cell transplant recipients (06 Dec 2013).

http://tagbasicscienceproject.typepad.com

References:

1. Lazar K. HIV virus returns after cure hope rose: 2 Boston patients had transplants of marrow, halted powerful drugs. Boston Globe. (06 December 2013).
   http://www.bostonglobe.com/lifestyle/health-wellness/2013/12/05/hiv-virus-returns-after-cure-hope-rose/kSUyH1YkgJ27AP4aZwpUXJ/story.html
2. Henrich T et al. Long-term reduction in peripheral blood HIV-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation in two HIV-positive individuals. 19th International AIDS Conference, 22-27 July 2012, Washington. Abstract THAA0101.
   http://pag.aids2012.org/abstracts.aspx?aid=6016 (Abstract)
   http://pag.aids2012.org/flash.aspx?pid=1379 (Webcast)
3. Henrich T et al. Long-term reduction in peripheral blood HIV type-1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J Infect Dis. (2013) 207 (11): 1694-1702. doi: 10.1093/infdis/jit086.
   http://jid.oxfordjournals.org/content/207/11/1694.long
4. Henrich T. Long-term reduction in peripheral blood HIV-1 reservoirs following reduced intensity conditioning allogenic stem cell transplantation in two HIV-infected individuals. IAS Search for a Cure symposium. Kuala Lumpur, 28-29 June 2013. S6.3.
   http://www.youtube.com/watch?v=okPVcipjInY&feature=youtu.be (video presentation)
5. Conference on Retroviruses and Opportunistic Infections (CROI) 2014. 3-6 March 2014, Boston.
   http://www.croi2014.org