What's Behind Lower Risk of HIV in Sickle Cell Disease?

Although African-Americans have the some of the highest rates of HIV in the United States, sickle cell disease (SCD)—which affects an estimated 1 out of every 365 African-American babies born in the US—seems to offer some protection from HIV. The reasons for this are not fully understood.

In an effort to further explore this phenomenon, a team of investigators published an analysis of existing data as well as a new study of immune cells from people without HIV in order to determine the reasons behind the lower rates of HIV in people with sickle cell disease. The findings were published in PLOS One.

Scientists at Vitalant Research Institute in San Francisco delved deeply into the Transfusion Safety Study, a years-long trial from the 1980s and 1990s conducted by the National Heart, Lung, and Blood Institute. The Transfusion Safety Study followed patients who had received blood transfusions)—as well as controls who hadn’t received transfusions)—to monitor for HIV infection. The blood supply was not as carefully monitored in the 1980s as it is today, with donors now being screened for HIV and other infectious diseases.

The participants in the transfusion study included 274 people who suffered from various anemias, including sickle cell disease, thalassemia and Diamond-Blackfan anemia. At the study’s start, just 1 out of the 143 previously transfused subjects with sickle cell disease had HIV, while 20 out of 131 of those with either thalassemia or Diamond-Blackfan anemia were HIV positive.

To confirm that sickle cell disease is linked with lower levels of HIV than are non-sickle cell anemias)—and to try to pinpoint the underlying reasons for this)—the Vitalant investigators conducted their own study. They enrolled 30 participants with sickle cell disease and 30 participants without sickle cell disease, all African-American, in order to analyze blood samples and figure out the mechanisms of HIV resistance in people with sickle cell disease.

The study team theorized that people with sickle cell disease have a lower chance of contracting HIV because co-receptors proteins might be less expressive and CD4+ T cells less active; however, the results did not necessarily bear this out.

“We first investigated if SCD patients differed in their expression of markers associated with HIV entry into CD4+ T cells (CCR5, CXCR4) or cellular markers of activation (CD38 and HLA-DR),” the study authors wrote.

“We demonstrated significantly lower expression of CCR5 in SCD patients, which was interesting as CCR5-tropic strains of HIV are generally associated with HIV transmission. Despite the fact that SCD patients showed higher levels of immune activation as a consequence of their disease, these data pointed to a potential for lower levels of infection due to the decreased expression of the critical HIV co-receptor. Even so, the in vitro experiments did not show decreased susceptibility in SCD CD4+ T cells compared to controls, so the in vivo significance of lower CCR5 expression on CD4+ T cells in SCD is unclear.”

Not only do people with sickle cell disease acquire HIV at lower rates than their counterparts, they also seem to experience a slower progression of disease, with lower viral loads and fewer deaths due to AIDS. This has relevance for future treatments and merits further study.

The investigators noted that although their recent study centered on CD4+ T cells and their response to HIV, other cells might come into play.

“Unlocking these mechanisms of HIV resistance is important not only for understanding the interplay of SCD pathophysiology with potential infections in persons with SCD, but also for identification of potential therapeutic targets for HIV in general.”