Home institution: University of Zimbabwe
US Institution: Stanford University
Project Title: Immunogenetics of disease progression in HIV perinatally infected children in sub-Saharan Africa.
There are 2.5 million children living with HIV and the vast majority of these children acquired infection perinatally. Although antiretroviral therapy (ART) is effective there are significant adherence and cost challenges associated with lifelong therapy in children. Drug sparing approaches such as therapeutic vaccines are needed for infected children. These strategies would try to achieve functional cure status in children resulting in an immunologic phenotype that closely resembles that of HIV elite controllers who maintain undetectable viral loads in the absence of ART. The determinants of immune control and disease progression among HIV infected African children remain poorly understood. To help explain the variability in disease progression, several studies have examined the roles of viral factors, the innate and adaptive immune response and host genetic factors. Host genetic variation is currently estimated to account for about a quarter of the observed variation in HIV control. Among the genetic factors involved in the immune response to HIV, the human leucocyte antigens (HLAs) have the strongest influence. Natural killer cell receptors are also important in the innate response to HIV infection and may have a role in disease progression. There is limited data on HLA genotypes among Zimbabweans and no data on the role that HLA alleles may have in disease progression in perinatally infected children and adolescents. Given this background, this study is aimed at evaluating the impact of host genetics on HIV/AIDS progression conferred by the polymorphic immune response loci. This is a sub project nested within a broader project that will also characterize the function and phenotype of CD4+ and CD8+ T cell responses, determine the role of the thymus and IL-7 in maintaining T cell homeostasis in perinatally infected long-term non progressors, age-matched slow progressors and rapid progress ors.