When a viral infection cannot be eradicated and becomes chronic, the immune system gets exhausted. Human studies have shown that lymphocytes that are exhausted by chronic HIV infection display greater numbers of a receptor called programmed death 1 (PD-1). In an in vitro study, researchers found that an antibody that blocked the ability of PD-1 to activate its suicidal signals allowed lymphocytes to fight HIV more effectively (JW Gen Med Oct 10 2006).
Nine monkeys were treated with partially humanized PD-1 antibodies at 10 weeks or at 90 weeks after they were infected with simian immunodeficiency virus (SIV; a cousin of HIV). Five SIV-infected control monkeys were treated with an antibody against another receptor. The active treatment greatly increased the numbers and the function of both virus-specific CD8+ T cells and memory B cells. Treatment also greatly reduced viral load and led to a remarkable difference in mortality: 150 days after treatment, no treated monkeys, but four controls (80%), had died. Safety studies revealed no abnormalities in liver, kidney, or marrow in treated animals.