Another MHRP group is focused on threat assessment. MHRP conducts epidemiologic studies, identifies specific targets for preventive intervention, and prepares specific recommendations for program and policy changes that are intended to decrease HIV transmission among most at-risk populations across the Army. This threat assessment expertise can be useful diplomatically; for example, if AFRICOM [Africa Command] is trying to build a better relationship with the Nigerian military, we can go in, with established relationships, and help them determine prevalence and what types of HIV are circulating. The threat assessment group helps to build strategic relationships.”

The RV144 Vaccine Trial:
A First Sign that
We Might Win

The work of the MHRP’s immunologists and virologists has advanced the MHRP’s threat assessment capabilities and also laid the groundwork for pursuit of the program’s ambition to eliminate the threat of HIV/AIDS. In an unusual arrangement, WRAIR’s researchers include both early-stage clinical vaccine researchers, led by Dr. Merlin Robb, and a group that helps plan and conduct large scale efficacy studies, led by Kim.

The MHRP has been developing HIV vaccines for nearly 20 years. The program made history in 2003, when it launched a trial among more than 16,000 Thai subjects combining two vaccines. Vaccinated subjects were first given ALVAC-HIV, which uses a canarypox virus to introduce select HIV genes into the body, and then a booster of AIDSVAX B/E, a glycoprotein vaccine used in an earlier Bangkok trial.

When the subjects of this trial, known as RV144 or simply “the Thai trial,” were examined six years later, the results demonstrated that the ALVAC-HIV and AIDSVAX B/E “prime-boost” had lowered the rate of HIV infection by 31.2 percent, compared to those who had been given a placebo. “So there was evidence that the vaccine could actually protect against infections. It was the first time that had ever been seen,” said Kim, “the only clear demonstration of protection in humans. And that’s important, because, at the time, we were thinking protection might not even be possible. We were thinking that, at best, the vaccine might decrease the amount of virus in your blood if you got infected.”

After the RV144 trial, the most important question became: How did the vaccine work? A series of follow-on collaborations, involving 150 researchers from 27 institutes around the world, combed through RV144 results to generate hypotheses. The effort culminated in a study led by scientists from WRAIR and Duke University, who in 2012, reported the vaccine was triggering an immune response that targeted a vulnerable site on the virus’s protein coat, a site known as V2.

The methodical, deliberate pace of these collaborative events may obscure what likely will be regarded, when the final history of the HIV/AIDS vaccine is written, as a historic milestone: In the span of a decade, MHRP researchers and their partners have proven that protecting humans with an HIV vaccine is possible, and identified a point of attack for future vaccines and therapies. Already, clinical trials have been launched to build on these findings.

MHRP has developed a promising next-generation MVA vaccine in collaboration with the National Institutes of Allergy and Infectious Diseases (NIAID) Laboratory of Viral Diseases that is aimed at global protection (one whose efficacy is not limited to a regional subtype). The MVA vaccine is already being tested in combination with several vaccine candidates in the United States, Sweden, and East Africa. This MVA vaccine will be used in combination with an Ad26 vaccine in the United States in 2014 through a private-public collaboration.

Since 2004, the MHRP has provided prevention, care, and treatment services in the African communities in which research is conducted. These activities were undertaken at the insistence of former MHRP Director Debbi Birx, M.D., who put forth the idea – an unusually forward-thinking idea, at the time – that the program was ethically obligated to treat people who participated in clinical trials and later became infected with HIV. This eliminated potential coercion by offering treatment to all regardless of participation in HIV vaccine trials. At around the same time, the White House launched the President’s Emergency Plan for AIDS Relief (PEPFAR), which continues to fund MHRP’s effort to provide these services both in civilian communities and with militaries. “By setting up PEPFAR programs at each of our sites,” said Kim, “we now have the ability to offer treatment to everyone in the region.” In Tanzania, for example – where the military has had battalions decimated by HIV – MHRP partners have been invited to set up care and treatment programs at military hospitals. “That kind of relationship is a critical part of our engagement with foreign militaries,” Kim said. “It has strategic importance.”

As it continues to work toward an effective vaccine, MHRP’s research has turned its attention to another future goal: curing infected patients. This research, explained Kim, focuses on the early stages of infection – an emphasis for which MHRP’s vaccine work has laid the groundwork. “If you stop an invader on the beaches,” he said, “it’s a lot better than letting it land, set up camp, and establish itself. We were studying early infection in order to understand what we need to do to prevent the initial landing, or to contain it just after landing – but it turns out some of the research we were doing is ideally suited for the cure agenda.”

. “If you stop an invader on the beaches,” he said, “it’s a lot better than letting it land, set up camp, and establish itself. We were studying early infection in order to understand what we need to do to prevent the initial landing, or to contain it just after landing – but it turns out some of the research we were doing is ideally suited for the cure agenda.”

In one study, researchers initiated anti-retrovirals within the first days of infection and then intensively studied them. “These people now have no detectable virus at the limit that we can detect in their blood,” said Kim. In collaboration with other scientists from universities and the National Institutes of Health (NIH), MHRP researchers are designing interventions aimed at eradicating HIV before it can take hold. “All of these different efforts are ongoing,” he said, “and really exciting cutting-edge research has been done in the last year.”

Despite sharp reductions in infection rates – according to a United Nations 2012 report, HIV infections have fallen by 50 percent or more in 25 countries, with an additional 14 countries having achieved declines of 25 to 49 percent – HIV still infects 34 million people annually, posing a significant threat not only to military readiness and force protection, but also to the stability and security of many already struggling nations.

In June 2001, before a United Nations General Assembly special session on HIV/AIDS, Gen. Colin Powell, the former secretary of state and U.S. Army chief of staff, echoed the anxieties of his predecessors – Washington’s dread of smallpox, and MacArthur’s fear of malaria – when he said: “No war on the face of the Earth is more destructive than the AIDS pandemic.” A dozen years later, and 120 years after Army Surgeon General Brig. Gen. George M. Sternberg established an Army Medical School whose researchers ventured out to study the world’s most virulent diseases, there are, at last, signs that WRAIR’s Center for Infectious Disease Research may someday make these diseases – like smallpox, which WHO declared eradicated in 1979 – a thing of the past.

This article first appeared in Walter Reed Army Institute of Research: 120 Years of Advances for Military and Public Health.