Approximately 1.2 million Americans and 35 million people worldwide are currently living with HIV. For these individuals, and for those who will become infected with HIV in the next few years, any future vaccine will come too late, and effective antiviral therapies must be used to combat their HIV infections.
The application of therapies using combinations of antiviral drugs has shown that HIV replication in infected people can be suppressed, which provides considerable and long-lasting clinical improvement. These therapies have helped large numbers of infected patients live relatively normal lives. Most importantly, they validate the concept that antiviral drugs can offer long-term relief to patients with HIV infections. However, current therapies do not eliminate the virus from infected patients; thus, lifelong treatment is required. This long-term therapy is associated with a number of problems, including toxicity, poor patient compliance, and, in some cases, the appearance of drug-resistance mutations. There remains, therefore, an urgent need to understand how the virus develops resistance to drugs; this understanding can be used to develop more effective strategies and drugs for the treatment of HIV infections.
The HIV Dynamics and Replication Program (HIV DRP) was formed in 1997 as the HIV Drug Resistance Program, with the mission of conducting and fostering multidisciplinary basic, translational, and clinical research focused on problems related to drug-resistant HIV. The HIV DRP has built on the existing strengths of the NCI’s basic and clinical research programs in retrovirology, drug discovery, and AIDS, exploiting studies in structural biology, biochemistry, virology, virus-host interaction, evolution, and in vivo virus biology to better understand mechanisms of retroviral replication. These are areas of critical importance to the AIDS epidemic, and they raise both basic and clinical research challenges whose solution will enhance our understanding of fundamental aspects of virology and cell biology, and guide the development of more effective therapeutics and therapies. Although the Program focuses primarily on HIV, drug resistance is a major concern for other infectious agents as well as cancer, and it is likely that our research will be beneficial in these and other areas.
Because antiviral therapies are now relatively effective, some of the focus in the field, and within the HIV DRP, has shifted toward questions that include, but are not limited to, the interactions of HIV with the host. These include basic and molecular questions involving the host cell factors that HIV exploits during its replication and factors that the host cell uses to help control the replication of HIV and other viruses. There is also an interest in how the virus is able to persist in infected patients who have been successfully treated with antiviral drugs for many years. It now appears that some HIV-infected cells in patients can grow and divide. This clonal expansion helps the cells, and the viruses they carry, to persist, and may contribute to the reservoir that has made developing a cure for HIV infections a challenging goal.
The scope of research conducted by HIV DRP scientists has expanded over the years to encompass a broader range of important problems in retrovirus biology. Thus, in 2015, the name of the Program was changed to HIV Dynamics and Replication to better capture the breadth of the research carried out by the Program.
The HIV DRP comprises a basic research component (Retroviral Replication Laboratory) and a clinical component (Host-Virus Interaction Branch). Click on the links below to learn more about the investigators within each component.
Retroviral Replication Laboratory
Stephen H. Hughes, PhD
Alex Compton, PhD
Eric O. Freed, PhD
Wei-Shu Hu, PhD
Vinay K. Pathak, PhD
Alan Rein, PhD
Host-Virus Interaction Branch
Frank Maldarelli, MD, PhD
Mary Kearney, PhD