Ahmed's findings prompted Walker and his colleagues to explore the role of the PD-1 pathway in a large population of HIV-infected patients in the KwaZulu-Natal province of South Africa. The province is at the epicenter of the HIV epidemic in sub-Saharan Africa; a third of pregnant women there are infected with HIV. The researchers conducted much of their work at the Doris Duke Medical Research Institute in Durban. Durban is the largest city in KwaZulu-Natal, and HIV prevalence among pregnant women in the city exceeds 50 percent.
The studies at the lab in South Africa found that PD-1 was significantly activated in 71 HIV-infected patients who had not yet begun antiviral treatment. In a separate study, the researchers demonstrated that PD-1 is also activated in the T cells of people with Epstein-Barr virus, which is a persistent infection, but much lower on T cells of persons immunized with vaccinia virus, a live virus vaccine against smallpox that is effectively cleared by the immune system. According to Walker, those findings indicate that activation of the PD-1 pathway occurs during the immune system's general response to viral infection.
In test tube studies, the researchers showed that higher PD-1 expression was associated with more severe functional "exhaustion" of HIV-specific killer T cells. The studies clearly demonstrated that the greater the PD-1 expre