A recurring theme in HIV cure research is the barrier presented by latent HIV infection. Current antiretroviral therapy (ART) can reduce active virus growth to undetectable levels. But there remains an extremely stable reservoir of virus invulnerable to attack by these drugs.
One strategy to overcome this latent reservoir is to activate the latent cells, making the virus susceptible to ART. During the course of a prior ARCHE (amfAR Research Consortium on HIV Eradication) study, it was discovered that disulfiram, a drug that is approved by the FDA for the treatment of alcoholism, could activate latent HIV in the test tube. Dr. Julian Elliott of Monash University in Melbourne, Australia, along with Dr. Steven Deeks of the University of California, San Francisco, now plan to determine whether this concept could be effective in patients.
Drs. Elliot and Deeks will give different doses of disulfiram to four groups of 10 adult volunteers with stable HIV infection on ART, daily for three days. This is known as a dose escalation study. Apart from safety monitoring, they will evaluate the effect of this drug on the growth of HIV in T cells and plasma. They will also see if the size of a patient’s latent HIV reservoir is altered by treatment.
A second ARCHE grant was awarded to Dr. Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital. He will study two HIV-positive individuals who had been on long-term ART when they developed lymphomas. To treat their cancer, both underwent typical stem-cell transplants from donors who had been selected only for tissue-type match. But Dr. Henrich found something extraordinary. Not only were these individuals cured of their cancer, but he could find no evidence of HIV infection. While the “Berlin patient” was cured of HIV following transplant with cells from a donor selected for the CCR5 delta32 mutation, and thus HIV infection, in a procedure involving highly toxic total body radiation and anti-T cell antibodies, no extraordinary measures were used here. For the moment, these two individuals remain on ART. But with amfAR funding, Dr. Henrich will interrupt their ART and search for HIV in their blood and other tissues. He will also assess the size of their HIV reservoir if any latent virus is uncovered.
A third grant was awarded to Dr. Deborah Persaud of Johns Hopkins and Dr. Katherine Luzuriaga of the University of Massachusetts. They will determine if it is possible to cure an HIV infection with ART alone in children in whom ART had been started soon after birth and continued for an average of 15 years. Drs. Persaud and Luzuriaga have a group of five such children with no detectable HIV, who remain HIV antibody negative. The researchers will use highly sophisticated tests to search for active and latent virus.
We are very excited about the prospects of these three new studies to advance our goal of finding a practical cure for HIV/AIDS.
To view the press release click here.