17 May, 2016 08:28

In Pursuit Of An HIV Vaccine And The AIDS-Free Generation

In the US, many people speak of “the AIDS crisis” as though it were something that happened and is now over. We do have effective treatments, and increasingly effective means of prevention. They include new, once-a-day pills that are very effective at preventing HIV infection as long as they are taken daily.


So why do scientists like us continue to devote our professional lives to finding means of preventing HIV transmission? Because the HIV/AIDS crisis is anything but over—even here in the United States, even with the tools that are now available.

Alarmingly, a recent analysis by the CDC predicts that half of black gay men and a quarter of Latino gay men will be infected in their lifetimes. While African Americans make up only 12% of the U.S. population, they account for 44% of new HIV infections. Infection rates among black women are persistently higher than other groups. In 2014, more than 5,000 African American women were diagnosed with HIV, compared to fewer than 1,500 new diagnoses among Hispanic/Latino and white women.

A vaccine would be an indispensable tool in ending the HIV epidemic for good and biomedical research has gotten us closer than ever to that goal. We can’t afford to let up on those efforts.

Despite a deceptively appealing counter-narrative about the AIDS crisis in decline, in reality the number of people infected with HIV continues to climb year after year. There are now 1.2 million people living with HIV in the United States, and last year that number grew by more than 50,000. Today, nearly 13,000 people who die in the United States each year have AIDS. The lurking aspects of the epidemic are evidenced by sporadic microepidemics. This year 150 cases of HIV occurred within six months in Scott County, Indiana, an area with only one case in the prior two years.

Today’s American HIV/AIDS crisis does look different than it did in the 1980s and 1990s. Effective treatments allow HIV-positive individuals to lead long and productive lives, and pre-exposure prophylaxis, or PrEP, allows HIV-negative individuals at risk to take an antiviral every day to prevent infection. Programs to implement widespread HIV testing with immediate treatment (test and treat) are lowering the overall spread of the infection in affected communities. Such approaches have started to reduce the rate of HIV through the concerted effort of the public health agencies in many of our nation’s communities, including leaders like San Francisco.

These prevention strategies need to be continued; yet there is no precedent to expect such approaches to reduce infections to the levels seen with an effective vaccine. Daily drug regimens and behavioral changes are highly effective for those who can access and afford them and maintain their vigilance, but vaccines remain, in the long run both here in the U.S. and abroad, the most equitable and promising route to ending the health crisis that is the HIV/AIDS epidemic.

No one can deny that biomedical research into HIV/AIDS vaccines has followed a bumpy path over the past several decades. HIV, one of the trickiest diseases on the planet, has been a difficult adversary. But a renaissance is taking place in our understanding of the virus. Drugs that have demonstrated strong results in preventing and treating HIV are part of a new wave of therapies, and potential vaccine precursors have emerged that provide optimism that our sustained scientific efforts are paying off.

One of these recent scientific achievements has been the ability to identify, modify and manufacture broadly neutralizing antibodies to HIV and give them to people as a way of protecting them from acquiring HIV-1–a strategy called antibody mediated prevention (AMP). Basic research into how to isolate and clone single antibody cells has allowed us to discover that 10-12% of HIV-infected persons make broadly neutralizing antibodies. These antibodies can be characterized and manufactured in quantities that might make it possible to prevent HIV-1 infection in people at risk of acquiring it.

A clinical study funded by the National Institute of Allergy and Infectious Diseases and run jointly by the HIV Vaccine Trials Network and the HIV Prevention Trials Network to test how effective this approach is and what concentrations of antibodies work the best recently started in the United States. A sister trial is being started in sub-Saharan Africa. AMP, an antibody demonstrated to prevent most strains of HIV, is given directly to participants via intravenous drip.

The AMP study infuses these antibodies every two months. This approach can be simplified using viral vectors to deliver antibody genes to the body’s muscle cells, allowing these cells to make these protective antibodies on a continuing basis, an alternative strategy known as VIP (vectored immunoprophylaxis). Most vaccines work by inducing the body to make antibodies; AMP or VIP provides the antibodies that we eventually might hope an HIV-1 vaccine would elicit.

The antibody used in these novel approaches was developed by the NIH in 2011, tested in early clinical trials in 2014 and has now entered large-scale human trials in 2016; an impressive speed demonstrating the resolve of the HIV scientific community to develop better ways to prevent people from acquiring HIV.

The use of antibodies to prevent HIV-1 acquisition has the potential to be a game changer and would provide a proof of concept for a new approach to both vaccination and prevention against HIV. Once we know whether these antibodies work and what concentrations are optimal, methods to engineer them in an affordable, population-scalable manner can begin in earnest.

Whatever happens in the near term, the only way to ensure that our future is HIV-free is with a highly effective vaccine or a scalable affordable method of prevention such as VIP. At the moment, we have better tools than we have ever had to both treat and stem the tide of new infections. But they will not end the HIV epidemic on their own. Only a vaccine or antibody preparation, priced fairly and made broadly available, has a strong chance of doing that. And only a continued national commitment to biomedical research, across both the public and private sectors, will get us there.

Larry Corey is president and director emeritus of the Fred Hutchinson Cancer Research Center and principal investigator for the HIV Vaccine Trials Network. David Baltimore is president emeritus of the California Institute of Technology, where he is currently a professor of biology. In 1975, he was a winner of the Nobel Prize in Physiology or Medicine.


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