Purging Reservoirs of HIV

Dr. Robert SilicianoJune was a record month for publications from amfAR-funded researchers, with eight manuscripts published. All focused on elements of the primary goal of amfAR research funding: a cure for HIV.

Dr. Robert Siliciano of Johns Hopkins University set the tone in a review he co-authored in the journal, BioEssays. He discussed recent progress in one of the potential HIV cure strategies being pursued, namely the purging of reservoirs of dormant HIV (ordinarily safe from attack by anti-HIV drugs) focusing on drugs that might wake up the virus from this latent state. Additionally, Dr. Siliciano noted the many technical barriers to this approach, including measuring the extent to which such reactivation has occurred, how to kill infected cells once the virus has been reactivated, and estimating the size of these reservoirs.

In a separate paper published in the Journal of Virology, Dr. Siliciano and his colleagues describe a new technique for quantifying the number of virus particles in the blood. While this is not necessarily a direct indication of the size of the viral reservoir, it might allow researchers to gain a better understanding of the nature of the persistence of these reservoirs. Along those lines, Dr. Una O’Doherty and colleagues described in Virology their work on 2-LTR circles, a DNA form of the virus that has received a lot of attention because it has been used to address the question of whether or not virus in the reservoirs continues to replicate or lies dormant. Dr. O’Doherty’s research suggests that because this circular form of the virus persists longer than had previously been believed, it may not in fact answer the question of ongoing replication.

Dr. Timothy Henrich If ongoing replication does occur within reservoirs, one might be able to reduce their size by intensifying antiretroviral therapy (ART). This is usually attempted with supplemental ART. Drs. Shulman, Palmer and colleagues reported in Blood that while maraviroc, a drug that blocks the CCR5 protein, when added to normal ART, did not cause a decrease in the amount of virus present, patients did experience benefits to their immune system that collectively suggest an increased ability to fight the virus.

There has been great interest in the role of the CCR5 protein in curing HIV infection. Dr. Reem Berro and colleagues described in the Journal of Virology various naturally occurring conformations of the CCR5 protein that can affect how well CCR5-blocking drugs work.

Dr. Timothy Henrich of Harvard Medical School followed a very different approach. He studied two men who had HIV and later developed a lymph node cancer known as lymphoma. Both men underwent a stem-cell transplant in an attempt to cure their cancer. In the case of the “Berlin patient,” who was cured of his leukemia (and HIV) after such a transplant, the donated cells came from a highly unusual donor with a genetic mutation in which the protein CCR5 was not present, thus conferring protection from HIV infection.  These new Henrich cases, however, involved a “standard” transplant and a “reduced-intensity conditioning” regimen rather than the intense, potentially dangerous preparatory regimen of radiation, chemotherapy and immune suppressive agents used in the case of the Berlin patient. Reporting in the June issue of the Journal of Infectious Diseases, Henrich and his colleagues found a sustained decrease in the size of their peripheral reservoirs of HIV at 21 and 42 months after transplantation.

At those time points the patients were still on antiretroviral therapy. However, just a few weeks ago, at the International AIDS Society conference in Malaysia, Dr. Henrich reported stopping all of their anti-HIV medications. Now, the two men, 15 and eight weeks later, respectively, remain virus free. We will keep you updated on these exciting developments. (Click here for more on this story.)

Dr. Laurence is amfAR’s senior scientific consultant.
Dr. Johnston is amfAR’s vice president and director of research.