August 17, 2017
The strongest proof that HIV can be cured comes from the case of Timothy Brown, the "Berlin patient." That triumph was predicated on physicians taking advantage of nature's own experiment: the existence of a genetic mutation in a normal cell protein, CCR5, the main co-receptor that HIV uses to gain entry into a cell.
Such a mutation can render a person virtually impervious to HIV infection. Doctors destroyed Mr. Brown's own immune and blood-forming cells by radiation, drugs, and antibodies, and then replaced them with cells from a donor with the CCR5 mutation.
To date, however, this success has not been reproduced in other HIV-infected patients. This is because either they harbored a minority strain of HIV that uses a means of entering a cell other than CCR5, or they died too quickly from their underlying disease -- usually leukemia -- which is what necessitated a stem cell transplant in the first place. This has left open the question as to how much of a role the CCR5 mutation played in Mr. Brown's cure, versus factors such as the radiation, drugs, or immune cell attack on HIV by donor cells.
Unlike Mr. Brown, all three of these men received transplants from donors who did not have a CCR5 mutation. These men had undetectable viral loads on antiretroviral therapy for four to six years prior to their transplant, and were maintained on antiretroviral therapy (ART) post-transplant. As in Mr. Brown's case, the reason for transplantation was a blood cancer.
After the transplant, all three showed decreases in their anti-HIV antibody responses but, unlike Mr. Brown, these responses did not disappear. This is presumptive evidence of HIV persistence.
The men also had substantial reductions in measures of the latent viral reservoir, and two of the three had no measurable virus at 12 months post-transplant. One patient had a sudden and robust reappearance of virus four years after transplant, which doctors concluded may have been due to inadequate blood levels of ART.
These three cases confirm the ability of a stem cell transplant to "profoundly reduce" the size of the HIV reservoir to below the limits of ultrasensitive detection techniques. They also confirm the likelihood that CCR5 played a major role in Mr. Brown's cure, pointing toward an important role for gene therapy in HIV eradication. Moreover, they highlight the need, as the authors conclude, "to identify better markers predicting viral rebound" than current techniques.
Dr. Laurence is amfAR's senior scientific consultant.
[Note from TheBodyPRO.com: This article was originally published by amfAR on Aug. 3, 2017. We have cross-posted it with their permission.]
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