Miller School Researcher Leading International Study on HIV Infections in Infants
Savita Pahwa, M.D., a University of Miami Miller School of Medicine researcher, is leading a collaborative international study on HIV infections in infants and older children in search of new insights that could point to a cure for the worldwide epidemic.
“We are focusing on how the human immunodeficiency virus establishes itself in an infant’s cellular and tissue reservoirs, where it is invisible to antiretroviral therapy and the body’s immune system,” said Pahwa, professor of microbiology and immunology, pediatrics and medicine, and Director of the Miami Center for AIDS Research (CFAR). There is increasing evidence that the sooner the treatment is started after infection, the smaller the reservoir, she said.
Unlike with adults, estimating the timing of HIV infection is more precise in infants, as it coincides with time of birth in most cases, said Pahwa, who was recently awarded a $3.2 million five-year grant from the National Institutes of Health for an international study, “Immunity and HIV Persistence in Perinatal HIV Infection.” The goal is to understand the relationship between time of infection, development of immune response, formation of reservoirs and timing of antiretroviral therapy (ART) initiation in infants.
Pahwa said more than 200,000 babies are born each year with HIV infections, primarily in resource-poor nations where HIV-infected pregnant women do not receive ART that can prevent HIV transmission to their babies. She will collaborate with Dr. Maria Grazia Lain, who oversees the pediatric program at F. Ariel, an independent Mozambican foundation whose mission is the elimination of pediatric HIV/AIDS in Mozambique, where approximately 6 percent of babies born to HIV-infected women are diagnosed as infected.
“We will study 40 babies in Maputo Province who have been diagnosed as HIV-infected and will start ART within two months of their birth,” Pahwa said. “The babies will be followed until two years of age to capture the influence of routine childhood vaccines on the immune system and virus reservoirs. We are particularly interested in a particular CD4 cell subset, known as T follicular helper cells, which are a major target of HIV infection and persistence, and which are also the biologic cell subset that helps B cells to produce antibodies in response to vaccines. A control group of 40 HIV-exposed but uninfected babies will be followed in the same way.”
In addition, Pahwa will work closely with Dr. Paolo Palma, who oversees the pediatric HIV and immunology program at Rome’s Bambino Gesu Hospital, one of the largest pediatric hospitals in Italy. “We will study 25 HIV-infected children and adolescents aged 5-18 years to investigate the effect of long-term antiretroviral therapy that had been started early in life,” she said.
Blood sampling and clinical follow-up of participants will be performed in Mozambique and Rome, and laboratory studies will be conducted on shipped samples in Rome and Miami. In Miami the studies will be performed by Pahwa and co-investigator Suresh Pallikkuth, Ph.D., using the resources of the laboratory of the Miami Center for AIDS Research, one of only 20 CFARs in the country and the only one in Florida.
Pahwa added that the Miami CFAR is also participating in the global project EPIICAL (Early Treated Perinatally HIV Infected Individuals: Improving Children’s Actual Life), under the leadership of Paolo Rossi, M.D., and Carlo Giaquinto, M.D., in Italy, with 24 partner centers. “Ours is one of two U.S. centers assigned as partners to conduct immunology investigations in blood samples collected retrospectively and prospectively from early treated HIV-infected children,” Pahwa said.
The project is being funded by ViiV Healthcare, a pharmaceutical company specializing in the development of therapies for HIV that was created in 2009 as a joint venture between Pfizer and GlaxoSmithKline.
Reflecting on the new five-year study, Pahwa said, “Our team has a unique opportunity to do incisive investigations in very well characterized and carefully monitored participants. This study will increase our knowledge about several aspects of HIV persistence and will drive the field toward vaccines and an eventual cure.”
This research is supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI127347.