A Potential New Target for Eradication of HIV Reservoirs
By Jeffrey Laurence, M.D.
In the January update we featured research led by amfAR-funded scientists at Case Western Reserve University on an FDA-approved drug, ruxolitinib, used in the experimental treatment of lymphoma. Writing in the February issue of the journal PLoS Pathogens, Drs. Timothy Henrich and colleagues at the amfAR Institute for HIV Cure Research at the University of California, San Francisco, and at Harvard University, continue this concept of evaluating anti-cancer drugs in anti-HIV strategies.
Dr. Timothy HenrichThe investigators studied the FDA-approved drug brentuximab (Adcetris). It is a toxin linked to a monoclonal antibody in order to target the activity of that toxin to cells that express the molecule CD30 on their surface. The drug is an important part of the treatment of resistant Hodgkin disease, a type of cancer, and certain other types of aggressive lymphoma. Fortunately, its target is highly expressed on certain tumor cells, but on only a very small percentage of normal cells. Dr. Henrich and his colleagues took advantage of the fact that other researchers had reported high levels of CD30 in patients with untreated HIV infection.
Henrich and colleagues now document that HIV is highly enriched in CD4+ T cells expressing CD30 obtained from HIV-infected individuals, regardless of whether or not they are on suppressive antiretroviral therapy (ART). Furthermore, exposure of T lymphocytes obtained from these individuals to brentuximab in the test tube reduces the amount of HIV DNA—a measure of virus reservoir size.
Their studies also addressed the question of HIV reservoirs in tissue. Active HIV in gut samples obtained from some of the patients was concentrated in CD30 positive cells.
Bringing this research back to the patient, the investigators studied an HIV-infected individual given brentuximab for his lymphoma. He had no detectable virus in his blood after six cycles of treatment. This was unexpected, as HIV-infected individuals receiving other types of chemotherapy do not lack detectable HIV. Although brentuximab has serious side effects and must be given as an intravenous infusion, limiting its applicability for HIV-positive individuals who don’t require it for cancer treatment, the authors rightly conclude that “CD30 is a potential therapeutic target of persistent HIV-1 infection.”
Dr. Laurence is amfAR’s senior scientific consultant.