International study investigates early biology of HIV infection

In July 2005, the race to find a vaccine that would stem the worldwide rate of 13,000 new cases of HIV infection each day moved from competition among research institutions to a strategy of cooperation.

An international “virtual research center” – the Center for HIV/AIDS Vaccine Immunology (CHAVI) – was awarded up to $300 million over seven years to support efforts to develop an HIV vaccine.

The first of several research studies in this collaboration now is under way and is aimed at gaining new knowledge into the biology of HIV infection during its earliest days, before the immune system has produced antibodies to the virus.

Dr. Myron S. Cohen, the J. Herbert Bate distinguished professor of medicine, microbiology, immunology and public health at the University of North Carolina at Chapel Hill, leads the new study.

A grant from the National Institute of Allergy and Infectious Diseases, a component of the National Institutes of Health, established CHAVI at Duke University under the leadership of Dr. Barton Haynes, Frederic M. Hanes professor of medicine and immunology at Duke University Medical Center and director of the Duke Human Vaccine Institute.

The UNC Center for Infectious Diseases, which Cohen directs, has pioneered the development of techniques to recognize patients with the earliest phase of HIV. Cohen and his colleagues have conducted HIV research internationally for more than a decade at clinical sites in Madagascar, China, Malawi, Cameroon and South Africa.

More than two decades after AIDS and the virus that causes it were first identified, an effective vaccine to halt the spread of HIV infection remains elusive.

“Until we know more about the transmission of HIV and early immune response, how the human body responds to the virus and how the virus behaves, we will have great difficulty in developing an effective vaccine,” Cohen said.

CHAVI investigators at institutions across the globe including the University of Oxford, Harvard University, the University of Alabama at Birmingham and UNC have agreed to share their expertise, technology, funding and findings.

“CHAVI’s goal is to conduct research that overcomes current barriers to AIDS vaccine development. These barriers include understanding which of the body’s immune responses to stimulate in order to fight off HIV-1 and understanding the specific type of virus that is transmitted from person to person,” Haynes said.

Cohen, a member of CHAVI’s Scientific Leadership Group, leads the center’s Study Site Core B, also known as the Acute HIV-1 Infections Network Core. This is one of five study cores in support of the vaccine initiative.

Cohen described the project, CHAVI-001, as an observational study that will gather information at clinics in Africa (Malawi and South Africa) and in North Carolina, where patients statewide will be referred to UNC and Duke. The initial goal of CHAVI-001 is to identify people with HIV still in its earliest stages, before seroconversion.

When people develop antibodies to HIV, they “seroconvert” from antibody-negative to antibody-positive, a process that may take from as little as a few weeks to several months or more after infection with HIV.

During the study, each individual’s health will be tracked, and interviews aimed at identifying their sexual partners will try to determine the person who transmitted the disease, thus completing a “transmission pair.”

“Since the epidemic began 25 years ago, only about 1,000 people in the earliest stages of HIV infection have been identified,” Cohen said. “Even more troubling, only a handful of transmission pairs have been reported. CHAVI has the resources to find them in substantial numbers.”

According to Cohen, knowledge of the viral requirements for transmission is crucial to understanding how to make a vaccine against HIV. That’s why one needs HIV both from the recipient and the person who transmitted it.

Also important to vaccine development is knowledge of the immunological environment in which transmission occurred, Cohen said. This means determining as close as possible to the time of transmission the kind of immune defenses that can restrain viral replication.

“We know that while the host defenses are not going to eliminate the virus, they can achieve some measure of control,” Cohen said. “When the control is achieved, the viral growth level is called the ’set point.’ We know that people who’ve achieved a lower set point – that is, better control of their virus – are likely on average to live longer healthier lives and seem to be less likely to transmit the virus to their sexual partners.”

Cohen said that along with studying the virus and immunological defenses, CHAVI also has the resources to study genetic factors that may be involved in HIV acquisition, including host genetic factors influencing infection and early progression of HIV-1 disease.

“CHAVI-001 will probably be able to study enough people so that genetics and the genetics of HIV acquisition and set points can be investigated.”

There are six sites for CHAVI-001: in Malawi, one in Llongwe and one in Blantyre; in South Africa, one in Johannesburg and one in Durban; and in North Carolina, one at UNC and one at Duke.