May was a banner month for publications reporting on the progress of amfAR-funded researchers, with seven different teams reporting in five prestigious scientific journals. Four of these scientists led studies exploring two major themes in HIV cure research: eradication of HIV reservoirs, those silent pockets of virus that are impervious to current anti-HIV drugs; and pragmatic approaches to replicating the success of the “Berlin patient” through genetic engineering-based targeting of the CCR5 virus receptor.
First, reporting in Current Opinion in HIV and AIDS, Dr. Keith Jerome of the Fred Hutchinson Cancer Research Center in Seattle, Washington, a member of the amfAR-supported ARCHE consortium, described specific genetic engineering tools that can disrupt CCR5, a key entry point for HIV infection of a cell. This was the gene naturally altered in the donor whose bone marrow was transplanted into the “Berlin patient.” The transplant was most likely a critical element in his cure. Most importantly, Dr. Jerome and his colleagues raise the prospect of a “one-shot” curative therapy, not requiring the expensive, technology-intensive, and risky procedures associated with a stem-cell transplant.
Another ARCHE member, Dr. Steven Deeks of the University of California-San Francisco (UCSF), and his colleagues at multiple institutions, including fellow amfAR grantees, Drs. Douek, Palmer, Pillai, J. Siliciano, R. Siliciano, and Richman, performed a comprehensive analysis of the “Berlin patient,” who is now five years off all anti-HIV drugs. Writing in PLOS Pathogens, they confirm his clinical cure, while advocating the development of even more sensitive assays to detect various forms of HIV, active and latent, in order to facilitate documentation of potential HIV cures. This area of investigation is currently being explored by other amfAR-funded scientists.
On the issue of HIV latency and viral reservoirs—untouchable by current drug strategies—Dr. Hiroyu Hatano, also of UCSF, suggests that the overactive immune systems that characterize most HIV-positive individuals, on or off highly active antiretroviral therapy (HAART), may promote reservoir persistence. Dr. Hatano’s review was published in Current Opinion in HIV and AIDS.She suggests interventions to treat co-infections and directly target immune activation.
Finally, amfAR grantee, Dr. Koh Fujinaga of UCSF and colleagues at the Chinese Academy of Sciences in Beijing describe a mechanism by which the reactivation of dormant HIV might be accomplished with anti-cancer drugs known as HDAC inhibitors. Dr. Fujinaga’s work was published in the Journal of Biological Chemistry,
Finding a cure for HIV remains at the top of amfAR’s research agenda. Along the path toward that goal, however, amfAR grantees are uncovering important information about the nature of the virus, which may lead to new, more effective treatment options in the future. As Dr. Jerome concluded in his report, such therapies “not only would give infected patients hope of a drug-free or treatment-free future, but also could reduce the huge financial burden faced by many countries because of widespread administration of highly active antiretroviral therapy.”
Dr. Laurence is amfAR’s senior scientific consultant.