Blocking T-Cell Growth: Will It Shrink the Reservoir?
By Jeffrey Laurence, M.D.
Although the size of the HIV reservoir remains stable during the course of chronic infection, individual reservoir cells and populations wax and wane. Some cells die off, which means there must be a counterbalancing growth in other reservoir cells. If this proliferation of reservoir cells could be prevented, the natural ongoing depletion of reservoir cells could, over time, result in clearance of the reservoir.
Four men living with HIV, between the ages of 26 and 62, who had maintained HIV suppression on ART for 5–19 years, completed this small “pilot” clinical trial. (One individual started on the trial stopped for “personal reasons.”) All four received twice daily, relatively low oral doses of the T-cell immune suppressant drug mycophenolate (also known as MMF or CellCept), which acts as an immune cell anti-proliferative agent. It is widely used in bone marrow and kidney transplant patients to inhibit graft rejection. The drug was continued for 48 weeks and its effect on HIV reservoirs was assessed by determining the level of intact HIV DNA in T cells in blood and biopsies of the rectum. No reduction in the size or composition of HIV reservoirs was found.
The authors concluded that “despite strong evidence that cellular proliferation maintains the reservoir…low-dose MMF did not reduce the HIV reservoir when given for almost a year.” They also noted, however, that the dosage of mycophenolate used was insufficient to maintain T-cell suppression; there were highs and lows of effect throughout each day of treatment. Therefore, “further studies, using higher doses, extended-release formulations, or other combinations of T cell anti-proliferative agents are warranted.”
amfAR was a funder of this research. Authors of this paper include amfAR grantees Drs. Joshua T. Schiffer, Keith Jerome, Robert D. Harrington, and Florian Hladik of the University of Washington in Seattle.
Dr. Laurence is amfAR’s senior scientific consultant.