As the clinical arm of the HIV Dynamics and Replication Program (HIV DRP, formerly the HIV Drug Resistance Program), the Host-Virus Interaction Branch (HVIB) conducts fundamental studies on the nature of HIV drug resistance in vivo. The HVIB has developed sensitive and specific tools that are being used to address questions of HIV-1 population genetics, replication dynamics, and emergence of resistance in infected individuals. Ongoing studies are focused on the following objectives: characterizing the replicating population size and genetics of HIV in infected individuals before, during, and after antiretroviral therapy (ART); defining the genetic mechanisms, kinetics of emergence and decay, and clinical consequences of HIV drug resistance; identifying the tissue and cellular sources of persistent viremia despite suppressive ART; and testing novel therapeutics to reduce persistent viremia and deplete HIV reservoirs.
The HVIB comprises several elements.
The Clinical Retrovirology Section, headed by Dr. Frank Maldarelli, directs the protocol development, regulatory affairs, patient recruitment, and sample collection effort for the HVIB at the NIH Clinical Center, in collaboration with the AIDS clinical research programs of the National Cancer Institute (HAMB, Dr. Robert Yarchoan), the National Institute of Allergy and Infectious Diseases (Dr. H. Clifford Lane), and the Critical Care Medicine Department (Dr. Henry Masur). The Clinical Retrovirology Section also conducts fundamental studies of HIV pathogenesis in vivo, including studies of HIV genetic variation and the emergence of antiretroviral drug resistance.
The Translational Research Unit, led by Dr. Mary Kearney, works in concert with the Clinical Retrovirology Section by developing and applying new technologies to characterize and identify sources of persistent HIV-1 viremia despite ART and to evaluate the impact of HIV-1 genetic diversity and low-frequency drug resistance mutations on response to ART. Dr. John Mellors (Chief, Division of Infectious Diseases, and Director, HIV/AIDS Program, University of Pittsburgh) provides critical consultation on all aspects of HIV clinical research, including protocol design and implementation. Dr. Mellors provides an invaluable interface with the extramural academic HIV/AIDS, including the AIDS Clinical Trials Group and international collaborative trials, making possible the Program's participation in major multicenter trials. The Mellors laboratory also collaborates closely with the HVIB on development of novel laboratory techniques for analysis of clinical material, and in basic studies of the mechanism of resistance to reverse transcriptase inhibitors. Dr. John Coffin (American Cancer Society Research Professor of Molecular Biology and Microbiology at Tufts University and founding Director of the HIV DRP) now serves as advisor to the Director of the Center for Cancer Research and consultant to the clinical program, providing critical advice on all aspects of the HVIB's research, particularly in the areas of assay design, development, and evaluation; data analysis and interpretation; and basic and clinical research approaches.