DEPARTMENT OF PATHOLOGY

Douglas D. Richman, M.D.

Douglas D. Richman, M.D.

  • Distinguished Professor
  • Director of the AIDS Research Institute, Veteran's Administration
  • M.D. - Stanford University
  • Residency Training: Stanford University Hospitals
  • Board Certifications: Internal Medicine; Infectious Diseases

Research Interests

Dr. Richman trained in infectious diseases and medical virology with research on influenza virus, herpesviruses and hemorrhagic fever viruses before focusing on HIV in the 1980s. HIV drug resistance was originally recognized in his laboratory in 1988. In addition to his continuing interest in HIV treatment and drug resistance, his research interests have focused on HIV pathogenesis including the issues of viral latency and evolution.

Current research in Dr. Richman's laboratory focuses on the natural history and molecular pathogenesis of HIV in a cohort of acutely infected patients. These studies include the cell mediated and neutralizing antibody immune responses to HIV and the viral escape and evolution in response to these. With regard to neutralization escape, we are interested in the epitopes that elicit the neutralizing antibody responses to autologous virus in human infections and the viral mutations that account for escape from these responses. We are also interested in characterizing the epitopes that elicit the too infrequent broadly reactive neutralizing responses in some patients. This information is central for the development of an effective HIV vaccine.

In addition virologic investigations include studies of HIV drug resistance, the pathogenetic consequences of virus replication in anatomic compartments and viral latency. Blood plasma, latently infected CD4 T lymphocytes, genital secretions and cerebrospinal specimens are being obtained from patients who are well characterized clinically, virologically and immunologically. These studies address important issues like selective pressures on the evolution of the HIV populations in different body compartments and pathogenesis. They also have important clinical implications with regard to the natural history of disease and treatment.

Dr. Richman has made major clinical and laboratory contributions to the field of HIV/AIDS, which represent a model of translational medical research. He helped design and conduct the clinical evaluation of new drugs and treatment strategies, including the first trial of combination antiretroviral therapy and the initial study documenting the value of the strategy of rendering HIV RNA undetectable. Two areas of his laboratory investigations represent landmark studies in HIV research. His laboratory first identified HIV drug resistance. This was the scientific foundation for the development of combination antiretroviral therapies. Subsequent studies documented the impact of drug resistance on treatment failure, the presence of mixtures of different viral phenotypes and genotypes circulating in the same patient, the pre-existence of drug-resistant mutants in untreated patients, the impact of disease stage and viral replication on the rates of viral evolution, and the independent evolution of different populations of HIV in lymphoid tissues and the brain. These studies have had a broad impact on the development, evaluation and regulatory approval of drugs, and helped to establish the importance of drug resistance assays in the day-to-day management of infected patients. His laboratory also documented the existence of reservoirs of latently infected CD4 cells in patients who appeared to be "fully suppressed" on potent antiretroviral therapy. These observations have raised fundamental questions about T lymphocyte biology and viral replication that bridge to a basic understanding of viral pathogenesis. More recently, his laboratory elucidated the remarkable evolution of neutralizing antibody responses in HIV infection, providing important insights for the development of an effective HIV vaccine. He plays an authoritative and constructive role as a speaker on both basic and clinical subjects, a lead editor of the major textbook on clinical virology, organizer of major international meetings and chair of national and international committees.

Representative Publications

  1. Strain MC, Gunthard HF, Havlir DV, Ignacio CC, Smith DM, Leigh Brown AJ, Macaranas TR, Lym RY, Daly OA, Fischer M, Opravil M, Levine H, Bacheler L, Spina CA, Richman DD, Wong JK. Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: intrinsic stability predicts longlife persistence. Proc Natl Acad Sci USA 100:4819-4824, 2003
  2. Pillai SK, Good B, Pond SK, Wong JK, Strain MC, Richman DD, Smith DM. Semen-specific genetic characteristics of human immunodeficiency virus type 1 env. J Virol 79:1734-1742, 2005
  3. Frost SDW, Little SJ, Kosakovsky Pond SL, Chappey C, Liu Y, Wrin T, Petropoulos CJ, Richman DD. Characterization of HIV-1 envelope variation and neutralizing antibody responses during transmission of HIV-1 subtype B. J Virol 79:6523-6527, 2005
  4. Frost S, Wrin T, Smith D, Kosakovsky Pond S, Liu Y, Paxinos E, Chappey C, Galovich J, Beauchaine J, Petropoulos C, Little S, Richman D. Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection. Proc Natl Acad Sci USA 102:18514-18519, 2005
  5. Smith DM, Strain MC, Frost SDW, Pillai SK, Wong JK, Wrin T, Liu Y, Petropolous CJ, Daar ES, Little SJ, Richman DD. Lack of Neutralizing Antibody Response to HIV-1 Predisposes to Superinfection. Virology, 355, pp. 1-6, 2006
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Biography

Dr. Douglas Richman received his A.B. from Dartmouth College and went on to receive his M.D. at Stanford University where he completed his residency. He was a Research Associate in the Laboratory of Infectious Diseases at the NIH's National Institute of Allergy and Infectious Diseases and Clinical Fellow in the Division of Infectious Diseases, Beth Israel Hospital and Children's Hospital Medical Center of Harvard

Dr. Richman joined the University of California, San Diego (UCSD) in 1976 and is currently Professor of Pathology and Medicine, and holds the Florence Seeley Riford Chair In AIDS Research. He is Director of the Center for AIDS Research at UCSD and of the Research Center for AIDS and HIV Infections at the San Diego VA Healthcare System where he attends in infectious diseases and is Chief and Director of the Clinical Virology Laboratory. He is a Fellow of the American Association for the Advancement of Science, the American Association of Physicians, the American Clinical and Climatological Association, and the Infectious Disease Society of America. He is a member of the NIH AIDS Vaccine Research Committee.

Dr. Richman was the first to discover HIV drug resistance in his laboratory in 1988. He is an internationally recognized leader in the treatment of patients living with HIV/AIDS and is a world authority on HIV drug resistance. Dr. Richman has authored or co-authored over 500 scientific publications. He is a co-editor of Clinical Virology, a state of the art clinical reference book, the editor of Antiviral Drug Resistance, and serves on the editorial boards of numerous scientific journals, including the Journal of Virology and Antimicrobial Agents and Chemotherapy.

He is Director of the Center for AIDS Research at UCSD and staff physician at the VA San Diego Healthcare System. He trained as an infectious disease physician and medical virologist at Stanford, the NIH and Harvard before joining the faculty at UCSD in 1976. He has focused his investigation on HIV disease and pathogenesis for the past 20 years. His laboratory was the first to identify HIV drug resistance. The lab joined two others in identifying latently infected CD4 cells as the obstacle to eradication of HIV with potent antiretroviral therapy. Recently his lab described the dynamics of the neutralizing antibody response to HIV and the rapidity of viral escape and evolution in response to this selective pressure.

Dr. Richman is Professor of Pathology and Medicine at UCSD (University of California San Diego). He is Director of the Research Center for AIDS and HIV infection at the VA San Diego Healthcare System, where they will conduct its first HIV trial for the HIV viral entry inhibitor, BlockAide/CR, during 2004. Dr. Richman is also Director of the Center for AIDS Research at UCSD. He trained as an infectious disease physician and medical virologist at Stanford, the NIH (National Institutes of Health) and Harvard before joining the faculty at UCSD in 1976. He has focused his investigations on HIV disease and pathogenesis for the past 20 years. His laboratory was the first to identify HIV drug resistance and joined two other labs in identifying latently infected CD4 cells as the obstacle to eradication of HIV with potent antiretroviral therapy.

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