The introduction of potent antiretroviral therapy nearly 2 decades ago and the development since then of an effective arsenal of both treatment and prevention tools have sharply reduced the rates of new human immunodeficiency virus (HIV) infections as well as deaths from AIDS.
Despite these gains, however, Anthony Fauci, MD, director of the National Institutes of Allergy and Infectious Diseases (NIAID), argues forcefully that the disease will not be fully managed until a vaccine eradicates it.
“Therapy has been very effective. The infection rate is down and deaths are down. The problem is that we just do not reach every infected person who needs therapy. We can decrease the incidence of HIV, but we cannot control or eliminate it in a durable way without a vaccine,” he says.
In an opinion piece in the New England Journal of Medicine earlier this year, Fauci cited the conflicting evidence that buttresses his argument. On the one hand, he pointed to the 2013 Global Report of the Joint United Nations Program on HIV/AIDS, which showed that AIDS-related deaths and new HIV infections have fallen by about a third from their peaks. In particular, he noted that antiretroviral therapy (ART) had averted 5.4 million deaths in low- and middle-income countries between 1995 and 2012. At the same time, however, he pointed to data showing that only one-fourth of HIV-infected individuals in the United States have “successfully navigated the care continuum to achieve an undetectable viral load with ART. Thus, health interventions are failing 75% of infected persons in this country and larger percentages in other countries—a situation that cannot be allowed to continue.”1
“We have the tools in the perfect world to manage the disease, but there are behavioral challenges, problems with the health care system, and societal challenges such as stigmatization. There are multiple gaps in the healthcare system, including getting people into care and keeping them there. In places where homosexuality is outlawed, it makes it very difficult to reach out to the vulnerable individuals at high risk of infection. In some places, sex workers are prosecuted for even possessing a condom,” he says.
To date, the HIV Vaccine Trials Network (HVTN) has tested more than 20 vaccine products, or by another measure that includes regimens comprising various products, doses, and schedule combinations, conducted 48 vaccine trials, according to Larry Corey, MD, head of the University of Washington’s Virology Division and the Fred Hutchinson Cancer Research Center’s Program in Infectious Diseases, and the principal investigator for the HVTN, an international collaboration of scientists and educators that conduct clinical trials around the world. The organization is backed by NIAID.
In conducting trials, the organization faces challenges that go well beyond the obvious scientific and technical ones, including some of the social barriers that treatment programs run up against.
“In our trials we have to deal with some issues more unique to the HIV field. For example, there is a lot of stigma associated with being in an HIV-related trial, and that makes it harder to enroll participants,” Corey says. “HIV-vaccine trials have the added complication of a phenomenon called vaccine-induced seropositivity (VISP), sometimes called vaccine-induced seroreactivity (VISR). Almost any HIV study vaccine will cause a person to develop antibodies to HIV, even if they are not infected. Because commercial HIV tests still only look at the presence of antibodies as proof of infection, study participants who are tested outside the study clinics can be diagnosed as HIV positive, with all the attendant difficulties such diagnosis presents. We explain this in our consent process and provide free testing that looks for the virus, not the antibodies, for as long as the person has VISP.”
Despite these hurdles, however, the organization is working to speed up the pace of trials as well as to expand the population of participants. Corey says the HVTN is developing novel trial designs, for example, aiming to reduce the length of time it takes a product to go from phase 1 through phase III testing or decrease the length of time it takes to determine which products in a group of several candidates should advance beyond phase 1.
“Another evolution of the HVTN over the years has been its expansion of studies in other fields, such as the social-behavioral field. For example, we try to tease apart barriers and facilitators to clinical trial participation among various populations and communities with which we work,” he says. “In addition, the HVTN has initiated a program called the Legacy Project to increase the participation of people of color in HIV vaccine trials. Our goal is to make sure the HIV vaccine works for the populations most affected by the virus.”