Surviving and Thriving 

 
 

Research and Care at UMMS

 

Sarah Cheeseman, MD

Sarah Cheeseman, MD

At the start of the AIDS epidemic, the University of Massachusetts Medical School (UMMS) was a very young institution.  Classes had only started in 1970; the hospital opened in 1976. And UMMS’ research program was just getting off the ground. In a remarkably short time, the institution established itself as a leader in HIV/AIDS research and treatment.

In 1978, John Sullivan, M.D. joined the Pediatrics Department at UMMS. He won his first R01 grant and set up his lab to study Epstein-Barr Virus (EBV) in 1981, the same year that the first reports on Kaposi’s Sarcoma (KS) and pneumocystis pneumonia (PCP) were published in the Morbidity and Mortality Weekly Report (MMWR). Within two years, he was seeing and treating infants with AIDS.

The nearby Worcester Memorial Hospital housed a large hemophilia treatment center, so Sullivan and fellow UMMS professor Sarah Cheeseman, M.D. (whose research focused on cytomegalovirus (CMV)) teamed up with Peter Levine, M.D. (Chief of Medicine at Worcester Memorial Hospital and Director of its New England Area Comprehensive Hemophilia Center) and Doreen Brettler, M.D. (Associate Director of the Hemophilia Center) to study the connections between hemophiliacs, EBV and CMV1. In 1984, they were part of a team that linked blood transfusion in hemophiliacs to AIDS transmission2.

The core of UMMS’ AIDS specialists continued to grow through the 80’s. Carol Bova, N.P., Ph.D., had trained as an RN specializing in oncology, but transferred to an HIV clinic in 1986 while pursuing her master’s degree. After graduating as a nurse practitioner (NP), she continued working with HIV/AIDS patients, helping them navigate clinical trials. Her research with Sarah Cheeseman revolved around helping HIV positive women adjust to chronic illness3. Richard Koup, M.D., the current chief of the NIH”s Immunology Laboratory served in a clinical fellowship (infectious diseases) at the Worcester Memorial Hospital and a research fellowship (viral immunology) for several years.

John Sullivan, MD

John Sullivan, MD

 

Katherine Luzuriaga, M.D., joined Sullivan’s lab in 1987, as a fellow in viral immunology. By then, treating AIDS was becoming a real possibility. A few drugs, like zidovudine (AZT) were being used to treat HIV/AIDS with some success. As part of the NIH’s AIDS Clinical Testing Group (ACTG), patients at the UMass HIV clinic had access to AZT as well as experimental treatments. That year, the pharmaceutical company Boehringer-Ingelheim recruited Bob Eckner, a professor and researcher at UMMS’ Microbiology and Radiation Oncology Department to develop a drug that could treat HIV/AIDS by inhibiting the replication of an enzyme called reverse transcriptase4. Eckner in turn recruited Sullivan for help screening potential drug compounds. Boehringer-Ingelheim gave UMMS the right to test one of those drugs, nevirapine. In conjunction with the ACTG UMMS began the first nevirapine clinical trial on January 21, 1991. That day, Cheeseman became the first physician to administer nevirapine to a human subject5. She directed the testing of the drug in adults, while Sullivan and Luzuriaga directed its simultaneous testing in children. Over the next several years, UMMS also conducted clinical trials to test nevirapine in adults and children, alone and in combination with AZT and didanosine (ddI). To reach more families, the three researchers set up clinics in Lowell and Lawrence, in addition to their work in Worcester.

 

Nevirapine proved to be a turning point in HIV/AIDS treatment. Alone and in combination, nevirapine prevents HIV from replicating and dramatically decreases the chances mother-to-child transmission of HIV in delivery. It is also inexpensive enough that it remains one of the most widely used AIDS drugs in the world. Cost was an important factor for Sullivan, who was concerned about pediatric AIDS as a global epidemic. In the mid 90’s, after the Phase 1 trial, Sullivan convinced Boehringer-Ingelheim to run a nevirapine trial in South Africa. The study results were presented at an international AIDS conference in 2000, and the company agreed to make the drug available free of charge to any country in the developing world to prevent mother-to-child transmission.

Continuing Research and Care @ UMMS

cropped UMassMed-Magazine-Year-In-Review-2013

Katherine Luzuriaga, MD

Luzuriaga, Sullivan, Cheeseman, and Bova are all still associated with UMMS working from bench to bedside and back again. Carol Bova earned her PhD and continues to work with HIV infected adults. She works with HIV positive patients with Hepatitis C to make informed decisions about their medical treatment and helped start a program around HIV education and prevention in Armenia with Carol Jaffarian, another UMMS nurse researcher. She holds appointments in both Nursing and Medicine as an associate professor. Sarah Cheeseman is a professor with the School of Medicine and the Graduate School of Biomedical Sciences. Sullivan likewise is a professor with the School of Medicine and the Graduate School of Biomedical Sciences. His lab focuses strongly on the development of therapeutics and vaccine regimens which can be used in the developing world to interrupt maternal to child transmission. He also played a major administrative role in UMMS’s winning a 5-year NIH grant to launch the Center for Clinical and Translational Science. He has held multiple positions, including the Chair of the Scientific Council, the Co-Chair of the Research Advisory Committee, the Director of the Office of Research, and Vice Provost for Research.

Luzuriaga made headlines this year for her work with Deborah Persaud, M.D. and Hannah Gay, MD. The three women were collectively named one of Time Magazine’s 100 Most Influential People in the World after they achieved a functional cure for a baby born with HIV6. The term “functional cure” means that the child appears healthy and HIV-free, although at this point there is no guarantee that this is a permanent cure. The child was born to an HIV positive mother who did not receive prenatal care. Rather than wait until the child tested HIV positive, the baby was treated with aggressive antiretroviral therapy for 18 months, when the mother stopped bringing the baby for treatments. The child later returned to the hospital, and even without follow up treatments, the team found no sign of HIV infection7.

 

Elizabeth Dodge, Linda Mangini and Carol Jaffarian.

Elizabeth Dodge, Linda Mangini and Carol Jaffarian.

 

Reading List

  1.  UMMC, Worcester Memorial Receive Major AIDS Grant. UMass Quarterly. 1983:1.
  2. Groopman JE, Salahuddin SZ, Sarngadharan MG, Mullins JI, Sullivan JL, Mulder C, et al. VIROLOGIC STUDIES IN A CASE OF TRANSFUSION-ASSOCIATED AIDS. New England Journal of Medicine. 1984;311(22):1419-22. PubMed PMID: WOS:A1984TT64500006.
  3. Oral History with Carol Bova, (2010).
  4. Oral History with John Sullivan, (2011).
  5. AIDS Drug Gets Green Light. UMMC Magazine. 1996:1.
  6. Dybul M. Hannah Gay, Katherine Luzuriaga and Deborah Persaud. Time. 2013.
  7. Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M, Chun TW, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013 Nov;369(19):1828-35. PubMed PMID: 24152233. eng.