CD8+ killer T cells are known to play a critical role in controlling the growth of HIV. But those cells, as produced during the course of an infection, are insufficiently potent to eliminate a persistent HIV infection, regardless of the use of antiretroviral therapy and strategies to induce—or “shock”—HIV from a dormant to an active state.
amfAR-funded scientists Clio Rooney, Cynthia Gay, Catherine Bollard, and David Margolis, working at the University of North Carolina at Chapel Hill and the Children’s National Health System in Washington, DC, along with colleagues from Baylor University, started a clinical trial aimed at overcoming obstacles to T cell-mediated clearance of HIV in ART-treated individuals.
Writing in the October issue of the journal Molecular Therapy, these investigators borrowed a page from the immunotherapy of cancer and certain viral infections. They removed T cells from HIV-infected individuals taking ART, and grew them to very large numbers in the presence of small pieces of HIV protein, immune hormones, and anti-HIV drugs (to prohibit the simultaneous growth of HIV). They then re-infused these “educated” cells—predominantly CD8+ killer T cells and so-called natural killer cells—into their original hosts on two occasions, two weeks apart.
Six subjects ranging in age from 35 to 65, on effective ART for 1 to 9.5 years, underwent this procedure known as adoptive T cell therapy. This first phase of the experiment was structured to evaluate the safety of the procedure. The infusions were well tolerated. As expected based on the study design, there was no change in the size of the latent HIV reservoir. The next step is to combine these infusions with a drug serving as a “latency-reversing agent” capable of inducing HIV growth from latent reservoirs. Such a clinical trial is already underway.
Dr. Laurence is amfAR’s senior scientific consultant.