A gene variant found almost exclusively in East Africa may provide protection from acquiring HIV-1 and inhibit the progression of the disease in those already infected.
A gene variant found almost exclusively in East Africa may provide protection from acquiring HIV-1 and inhibit the progression of the disease in those already infected. Researchers at the U.S. Military HIV Research Program (MHRP) reported the findings in the Journal of Infectious Diseases.
In collaboration with researchers from the University of Munich, Germany, and the Mbeya Medical Research Program, Tanzania, MHRP scientists analyzed data from a 42-month community-based cohort study already underway in southwestern Tanzania. The study involved 2,581 HIV negative individuals—104 of whom contracted HIV during the study—and 513 individuals who were HIV positive at the beginning of the study. Researchers genetically analyzed specimens from the cohort using a genotyping system developed by MHRP scientists tailored for the East African samples.
Researchers found that individuals with the HLA-A*7401 allele, a genetic variant of the class I HLA alleles, were less likely to get infected during the study than those who did not carry the allele. Additionally, among the individuals who were HIV positive when they entered the study, those with the A*7401 allele were less likely to have CD4 counts below 200 (a clinical measure of progression to AIDS), compared to those not carrying A*7401.
Although other alleles were also uncovered as protective or harmful, A*7401 remained exclusively associated with protection even when factors including gender, age and other socio-demographic features were considered. While A*7401 has recently been found protective in other contexts, this study confirms the protective role in a community-based setting where the risk for HIV infection is mainly heterosexual contact.
Genetic variation in class I HLA genes has been known to have profound consequences on many infectious diseases, including HIV. However, despite high HIV prevalence in East Africa, few studies have examined the effects of the HLA alleles on HIV-1 infection and disease course in this population. Furthermore, East Africa is one of the most genetically diverse regions in the world. The cohort in Tanzania, therefore, provided a unique forum to study the relationship between class I HLA variation and HIV-1 infection.
Understanding the protective or harmful effects of the class I HLA alleles present in the region is crucial. The HLA genetic background of a population poses challenges for designing vaccines against endemic pathogens, such as HIV, and can complicate the interpretation of results from vaccine trials. Furthermore, the effects of HLA alleles can be complicated by the genetic diversity of the virus. In Tanzania the epidemic is currently a mixed subtype epidemic, with the circulation of A, C, D and recombinant viruses.
Results from this study are important to the ongoing understanding of the human host’s interaction with the HIV virus in the quest to understand natural mechanisms to combat HIV infection. The implications of these results may help in the design of HIV vaccines for the region.