Four Pitt HIV Projects Get $11.5 Million in Funding From Gates Foundation

Researchers in the University of Pittsburgh schools of the health sciences and Magee-Womens Research Institute have been awarded four grants totaling nearly $11.5 million from the Bill & Melinda Gates Foundation.The foundation seeks to stop the spread of HIV by expanding access to successful prevention strategies and to identify and research new ways to prevent HIV transmission. More than 22 million new HIV infections will occur by 2015 despite the current decline in infection rates, according to the foundation. 

Descriptions of the grants follow.

A New Way of Detecting Infection

A first-of-its-kind collaboration between Pitt’s Center for Vaccine Research, Drug Discovery Institute, and Graduate School of Public Health received a $1 million, three-year grant to develop a novel test to detect HIV in the earliest stages of the disease.

5“The earlier you know about an infection, the quicker you can treat it,” said project principal investigator Donald S. Burke, who is dean of the Graduate School of Public Health, director of the Center for Vaccine Research, associate vice chancellor for global health, and UPMC-Jonas Salk Professor of Global Health at Pitt. “Immediately starting antiretroviral drugs greatly reduces the chance of the disease progressing to full-blown AIDS and reduces person-to-person transmissibility of the virus. The test will also enable extensive epidemiological studies in developing countries, allowing health agencies to effectively target their precious resources.”

Currently, tests rely on a few proteins made only by the HIV virus itself to detect anti-HIV antibodies in the blood. In new infections, these antibodies are typically at low levels, so it often takes months before a person tests positive for HIV—and sometimes years before the development of symptoms. The Pitt test is taking a new approach. Instead of looking only at proteins made by the virus, this research will examine a novel class of HIV biomarkers in patient blood samples. This approach utilizes synthetic molecules that resemble proteins and can be produced in millions of different variations. This larger diversity of biomarker targets increases the ability to detect new HIV infections and to distinguish between recent and established infections.

Such a test would allow public health workers to determine whether a Third World country’s HIV infections are a recent development and how fast the virus is spreading. Physicians could also factor in duration of infection to better tailor anti-HIV regimens.

Preventing HIV Infection With Monthly Injections

In the $4.5 million, two-year Options Now project, researchers will assess the acceptability and safety of injecting rilpivirine, a long-acting HIV drug, into the muscle of HIV-negative people with the aim of preventing infection. The research team is led by Ian McGowan, a professor of medicine and obstetrics, gynecology, and reproductive sciences in the Pitt School of Medicine. In addition, the research team includes Beatrice A. Chen, an assistant professor in the Department of Obstetrics, Gynecology, and Reproductive Sciences, Pitt School of Medicine, and Ross D. Cranston, a professor in the School of Medicine’s Division of Infectious Diseases.

“A system of regular injections, for example, has been shown to be acceptable, feasible, and effective for women worldwide as a method of pregnancy prevention,” said McGowan, who is also coprincipal investigator of the federally funded Microbicide Trials Network and a Magee-Womens Research Institute investigator. “We want to see whether this kind of strategy will be effective at reducing the risk of HIV infection.

”This summer, federal officials approved Truvada, another treatment drug, for use as an HIV prevention agent after two large studies showed it was effective in men who have sex with men and in couples in which one partner is HIV positive and the other is not. Researchers from the Microbicide Trials Network are waiting for results from a major clinical trial called VOICE, which will be key in determining whether Truvada is a viable prevention option for women. In the meantime, researchers are looking at other drug formulations, like topical gels, vaginal rings, and monthly injections that might be preferred over a daily pill and more apt to be used.

Exploring the Influence of Hormonal Contraception on HIV Infection

In a $5 million, three-year project led by Sharon Achilles, an assistant professor in the Pitt School of Medicine’s Department of Obstetrics, Gynecology, and Reproductive Sciences, scientists will examine whether hormonal contraceptive methods cause changes in genital tract immune cells, the cells that HIV targets for infection.

“Some studies have indicated that the use of birth-control shots, pills or other hormone-based contraception is associated with a higher risk for HIV,” Achilles said. “This presents a challenge because HIV prevention strategies and contraception should work together, rather than in opposition, to maximize the public health benefit.”

Achilles’ study will assess the impact of hormone-based contraception on the cells of the genital tract, particularly the immune cells that are targeted by HIV. In Harare, Zimbabwe, 250 healthy women who are initiating use of one of five commonly used contraceptives will be monitored for six months.

“Characterizing changes in the immune cells of the genital tract could inform the design of future clinical trials aimed at assessing contraception and HIV risk, as well as shape recommendations for women at high risk of HIV exposure,” Achilles said.

Coinvestigators include Sharon L. Hillier, a professor of obstetrics, gynecology, and reproductive sciences in Pitt’s School of Medicine and a senior investigator at Magee-Womens Research Institute, and Mike Chirenje of the University of Zimbabwe.

Distributing Anti-HIV Drugs to the Global Community

Lisa Cencia Rohan, a professor in Pitt’s School of Pharmacy and an investigator at Magee-Womens Research Institute, is leading a 15-month, $758,000 project that will assess the feasibility of thin-film dosage forms for vaginal delivery of contraceptive or HIV prevention drugs.

Rohan serves as coprincipal investigator with Hillier on a recently launched, early-stage clinical trial to test the safety of a vaginal film preparation containing a microbicide called dapivirine to ward off HIV infection. But before safety and efficacy trials can be expanded, Rohan noted, “it must be determined whether such a product can be successfully manufactured and distributed to resource-poor locations and what traits it must have to be acceptable to large numbers of users in a variety of settings.”