A genetic variation that may have protected people of African descent against a pandemic of malaria long ago now appears to increase their susceptibility to HIV infection, a report published this week shows.
The variation, described in the journal Cell Host & Microbe, is one of the first genetic risk factors for HIV to be identified only in those of African descent, and puts a spotlight on the differences in our genetic makeup that play a critical role in susceptibility to HIV-AIDS.
In a population of 1,266 HIV-positive U.S. military personnel and 2,000 non-infected healthy personnel, researchers studied the gene that expresses Duffy antigen receptor. This molecule on the surface of red blood cells serves as the docking site for the malaria species Plasmodium vivax.
“Subjects who have a genetic variation do not express Duffy antigen receptor and are known to be less likely to contract malaria vivax,” said Sunil K. Ahuja, M.D., professor at The University of Texas Health Science Center at San Antonio and a senior lead author of the study. “But now it turns out having this variation is a double-edged sword.”
“Duffy antigen influences levels of inflammatory and anti-HIV blood factors called chemokines,” noted Weijing He, M.D., senior post-doctoral fellow in Dr. Ahuja’s laboratory and first author of the paper. “Other as yet undefined host factors likely exert population-specific effects on HIV-AIDS, such that individuals of European or African descent are likely to have distinct host factors that affect their respective susceptibilities to HIV and AIDS.”
HIV affects 25 million people in sub-Saharan Africa today, an HIV burden greater than any other region of the world. Sexual behavior and other social factors do not fully explain the large discrepancy in HIV prevalence compared to populations worldwide, the authors note.
“In sub-Saharan Africa, the vast majority of people do not express Duffy on their red blood cells,” said senior lead author Robin A. Weiss, Ph.D., of University College London. “This is one of the first genetic factors particularly common in Africans that has been shown to confer more susceptibility to HIV.”
Paradoxically, the research team noted that once people become infected, the Duffy-deficient variation actually prolongs survival. Again, this was noted in the U.S. military personnel population.
“This is a clinical cohort of people who have been followed for nearly 25 years,” said a senior lead author, Matthew J. Dolan, M.D., of the Infectious Disease Clinical Research Program, Uniformed Services University, in Bethesda, Md. “The advantage is we have long-term follow-up, the population is ethnically balanced between European and African Americans, and everyone has had the same employer, health care and HIV medication access.”
Drs. Ahuja, He and Dolan; Hemant Kulkarni, M.D.; and other co-authors have published a series of papers on other genetic variations that play a role in HIV-AIDS susceptibility. “The Duffy finding is another valuable piece in the puzzle of HIV-AIDS genetics,” Dr. Ahuja said.