Molecular Virology

Feng Gao, MD

Highly active antiretroviral therapy (HAART) has been effective in reducing HIV-related mortality and morbidity. However, nearly half of HIV-infected patients still fail HAART. Genetic analyses of viral genomes from these patients show multiple-drug resistance mutations in the viral genes, but the molecular mechanisms for the emergence of drug-resistance are not yet known. Therefore, it is important to delineate the mechanisms for multiple-drug resistance in order to more effectively control HIV infection. To address this important issue, Dr. Gao’s team is studying the role of viral recombination in generation of multiple-drug resistance during HAART. The Gao laboratory has established a prospective clinical cohort and developed methods to analyze recombinant viral genomes within an infected individual.

They will:

genetically characterize the baseline viral population and determine their predictive values for treatment failure by sequencing multiple clones from each patient before HAART treatment;
determine the role of recombination in generation of multiple-drug resistance by comparing the drug-resistant viral population with the baseline viral population and identifying recombinant genomes; and
obtain viral populations before and after each treatment failure in the consecutive HAART regimes and analyze the dynamic changes of viral populations to determine mechanisms of repeated drug-resistance and fitness of drug-resistance viruses.

Understanding the viral population changes, drug-resistance mechanisms and viral fitness during HAART will allow for the development of more effective antiretroviral agents, better treatment regimens and accurate prediction of treatment efficacy. Knowledge obtained from this study can be broadly applied toward understanding mechanisms of viral escape from immune surveillance and other selective forces.