Robert M. Grant, MD, MPH

Senior Investigator

Betty Jean and Hiro Ogawa Endowed Investigator

Phone: (415) 734-4810
Fax: (415) 355-0855
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Professor, Medicine, University of California, San Francisco

Administrative Assistant

Malu Robles
(415) 734-4813
malu.robles@gladstone.ucsf.edu

More about Dr. Grant

Dr. Grant has more than 26 years of experience with AIDS clinical care and research, including four years in leading roles in epidemiological studies in both San Francisco and Uganda.

He is the protocol chair for the Pre-Exposure Prophylaxis Initiative (iPrEx) clinical trial, a multinational study with 11 research sites in six countries on four continents and the first one to demonstrate the efficacy of pre-exposure prophylaxis (PrEP) in the prevention of HIV infection. On the same line of research Dr. Grant’s laboratory is also leading research to understand the biological and social implications of PrEP such as the immune response due to exposure to the HIV viral-antigen, low-level drug resistance, alterations in HIV testing and disclosure on social networks.

Another area of interest of his laboratory includes HIV-1 superinfection, in which individuals already infected with HIV-1 might acquire additional strains of the virus. Understanding when superinfection does and does not occur could guide future HIV-vaccine development.

Dr. Grant’s team has also investigated the consequences of how viruses evolve over time. Specifically, they are examining the molecular mechanisms behind drug-resistant HIV-1 in terms of replication, virulence and transmission. They are also studying the non-life-threatening simian immunodeficiency virus infection in apes. The long-term goal is to understand the viral and social characteristics that underlie patterns of epidemic spread of HIV-1 in human communities.

Dr. Grant started the Gladstone/UCSF Laboratory of Clinical Virology in 1997 and the Gladstone Laboratory of Molecular Evolution in 2000. He has served as a member of the U.S. Food and Drug Administration Antiviral Advisory Committee and is an author of more than 100 peer-reviewed publications.

Dr. Grant earned a bachelor’s degree in biological sciences at Stanford University, an MPH in epidemiology at the University of California, Berkeley and an MD at UCSF, where he took his internship and residency training in medicine and did a fellowship in molecular medicine.

More scientific details, please

Other Professional Titles

Professor, Medicine, University of California, San Francisco

Administrative Assistant

Malu Robles
(415) 734-4813
malu.robles@gladstone.ucsf.edu

Areas of Investigation

Our laboratory focuses on the evaluation of Pre-Exposure Prophylaxis (or PrEP) for prevention of HIV transmission. This strategy involves the use of antiviral agents to block transmission of HIV-1 to highly exposed persons. We are currently involved in a global clinical trial with sites in Peru, Ecuador, Brazil, United States, South Africa and Thailand—settings where HIV-1 continues to spread despite widespread access to condoms, counseling and STD management.

We are also interested in HIV-1 superinfection, in which persons who are already infected with HIV-1 acquire additional strains of the virus. Superinfection may allow viruses to spread that are more drug resistant or more virulent. This is a significant concern for people with HIV infection, especially those in relationships with other infected persons. We are also studying mechanisms that may block superinfection in some persons as knowledge of these mechanisms may guide vaccine development.

Finally, we are investigating the evolution of the HIV virus, including:

  • the fitness of drug-resistant HIV-1 for replication, virulence and transmission;
  • selection pressures bearing on HIV-1 populations in tissues; and
  • nonpathogenic simian immunodeficiency virus (SIV) infection in natural host species.

These topics are studied in close coordination with the AIDS Research Institute-UCSF Laboratory of Clinical Virology, for which I am the Medical Director. Our long-term goal is to understand the viral and host characteristics that underlie patterns of epidemic spread of HIV-1 in human communities.

Current Lab Focus

  • Can daily oral use of generally safe antiviral agents serve to prevent acquisition of HIV infection?
  • Does exposure to antiviral agents early in the course of HIV-1 infection attenuate the course of infection by sparing anti-viral immune responses and lowering viral load?
  • Are some types of drug resistant HIV-1 more transmissible than others?
  • Does drug resistance affect virulence and host tissue range?
  • What is the frequency of HIV-1 superinfection?
  • Can superinfection spread HIV-1 that is more transmissible, drug resistant, or virulent?
  • How does the sex of the host affect viral evolution?
  • What viral characteristics are important for transmission between human hosts?
  • What viral and host proteins affect viral mutagenesis?

Joined Gladstone

1996

Why Gladstone?

Gladstone provides a uniquely supportive environment for creative initiatives having public health importance.

Key Achievements

  • Identified the first case of sexual transmission of HIV-1 resistant to multiple classes of antiretroviral therapy.
  • Found that transmitted drug resistance is becoming more common in San Francisco, which has served as a sentinel site for trends around the world.
  • Found that drug-resistant viremia is often associated with persistent partial immunological and virological responses to therapy. These partial responses were found to be dependent on continued exposure to drugs, which continue to have antiviral activity and select for viral variants with diminished replication capacity.
  • Discovered that multi-drug resistant HIV-1 variants are cytopathic for activated peripheral blood mononuclear cell cultures and lymphoid histocultures, but are associated with low viral load in nonlymphoid tissue compartments, like cerebrospinal fluid that bathes the brain.
  • Discovered that sooty mangabeys, a natural host for simian immunodeficiency virus, tolerate high level viremia for many years with no evidence of progressive or clinical immunodeficiency. Like humans, sooty mangabeys can have a null allele of CCR5, providing an example of parallel evolution within two lentiviral host species.

Education

Stanford University (BS, AB), Biological Sciences and Latin American Studies, with Honors (1983)
University of California, Berkeley (MPH, MS), Epidemiology and Health & Medical Sciences (1986)
University of California, San Francisco (MD), Medicine (1989)

Affiliations

Association of American Physicians
American Society of Clinical Investigation
Antiviral Drug Advisory Board of the Food and Drug Administration
Medical Director, AIDS Research Institute, University of California, San Francisco
American Board of Internal Medicine
American Board of Pulmonary Medicine
American College of Chest Physicians

Awards

  • Phi Beta Kappa, Stanford University (1982)
  • Honors, Latin American Studies, Stanford (1983)
  • University of California Regent’s Fellowship, University of California, Berkeley (1984)
  • Public Health Alumni Scholarship, University of California, Berkeley (1985)
  • Alpha Omega Alpha, School of Medicine, University of California, San (1988)
  • Mountain Scholarship, Marine Biological Laboratory, Woods Hole Oceanographic Institute (1994)
  • Molecular Medicine Training Program Fellowship, University of California, San Francisco (1994)
  • Delegate, United Nations General Assembly Special Session on HIV/AIDS (2006)
  • Betty Jean and Hiro Ogawa Endowed Investigator (2008)
  • San Francisco AIDS Foundation Leadership Award (2011)
  • Time Magazine’s Person Who Mattered (2011)
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Featured Publications

Robert M. Grant, MD, MPHLiu AY, Vittinghoff E, Sellmeyer DE, Irvin R, Mulligan K, Mayer K, Thompson M, Grant R, Pathak S, O'Hara B, Gvetadze R, Chillag K, Grohskopf L, Buchbinder SP. Bone mineral density in HIV-negative men participating in a tenofovir pre-exposure prophylaxis randomized clinical trial in San Francisco. PLoS One. 2011; 6(8):e23688. View in: PubMed
Robert M. Grant, MD, MPHGrant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapía M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernández T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallás EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30; 363(27):2587-99. View in: PubMed