Grant: Project Grant

HIV mutates rapidly in response to host immunity and antiretroviral therapy (ART). These mutations may have different impact on HIV disease progression and ART outcome. Some may impair viral fitness and slow down disease progression while others accelerate disease progression. Mutations driven by host immune responses or induced by ART may work alone or in combination to render ART ineffective, or predispose an individual to develop resistance to certain antiretroviral drugs (ARV). Current understanding of the interactions between the host immune response and ART on HIV viral mutation and fitness, and their impact on patient outcomes are very limited. There is no reference guide with such information that can be used to select the optimized ART regimens. The goal of our study is to fill this critical knowledge gap. By analyzing HIV full genome mutations before and after patients receiving ARVs, ART efficacies and disease status, we can understand how host immunity interacts with ART. We have assembled a research team with a proven track record of expertise and research experience in HIV and host genetics, HIV drug resistance, HIV evolution/fitness, and HIV clinical care. We will focus on two, predominantly female patient populations, a sex worker cohort in Kenya and a Canadian HIV+ patient population in Vancouver. We will: 1) analyze HIV sequences of these patients before and after ART by next generation sequencing technologies; 2) identify HIV mutations driven by host immunity alone or by ART using in-house bioinformatics tools; and 3) interpret their effect on disease progression and on ART effectiveness by integrating patient CD4, viral load, HLA profile, and HIV replication fitness data and statistics analysis. Mutations with impact on disease progression and ART will be mapped on the full HIV genome to generate a guide for precision patient treatment.