“Turning the Tide Together” was the slogan of the 19th International AIDS Conference (AIDS 2012), the world’s largest periodic gathering of HIV/AIDS researchers, held last July in Washington, D.C. The theme was an appropriate one: the tide within the HIV research community has indeed turned in recent years for the better. Let’s briefly review why.
As Diane Havlir, M.D. and Chris Beyrer, M.D., recently noted in the pages of The New England Journal of Medicine, “We are at a moment of extraordinary optimism in the response to [HIV].” They go on to highlight several factors driving this optimism: a sequence of scientific advances including several trials demonstrating the partial efficacy of oral and topical chemoprophylaxis and the first signs of efficacy for an HIV vaccine candidate; evidence for the first cure of an HIV-infected person; and the result that early initiation of anti-retroviral therapy can both enhance outcomes and lower the potential for HIV transmission to sexual partners by 96%. This latter advance, write Havlir and Beyrer, “has led many to assert what had so long seemed impossible: that control of the HIV pandemic may be achievable.”
Encouraging Trial Results
Indeed, significant progress is being made toward the creation of an effective vaccine. In autumn 2009, a collaborative effort between the Ministry of Health in Thailand, the U.S. Military, and the U.S. National Institute of Allergy and Infectious Disease (NIAID) announced the first encouraging results from an efficacy trial—31% prevention of infection in a 16,402-person community-based trial in Thailand. This result achieved significance in an analysis that excluded seven subjects who were found to have been infected at the time of the first vaccination, demonstrating for the first time that an HIV vaccine could prevent infection.
That trial, the third efficacy trial to be conducted for candidate HIV/AIDS vaccines, was the first to test a product designed to elicit both antibodies and T cells. This vaccine used a recombinant canarypox vaccine to prime immune responses plus protein subunits of the HIV surface protein to boost immune responses.
Additional analysis of the data suggested that protection—i.e., prevention of infection—had peaked at 60% at six months following the fourth and final vaccination, waned to 44% 12 months later, and to 34% by two years following the final vaccination—declines associated with decreasing levels of the antibody responses over time. Thus, this vaccine, if regularly boosted to maintain antibody responses, might have the potential to achieve approximately 60% prevention from infection—a credible level of protection for a new vaccine.
Until the Thai trial, many thought the best achievable outcome for an HIV/AIDS vaccine would be to induce immune responses capable of controlling, but not preventing, infection. The data from the Thai trial suggested that prevention from infection is a possibility.
With this encouraging news in the background, several companies are working toward an AIDS vaccine. Aventis-Pasteur and Global Solutions for Infectious Diseases, which supplied the vaccine for the successful Thai trial, are preparing product to test the ability of their vaccine, given with regular boosts, to protect Thai men who have sex with men. Additional efforts include those of GlaxoSmithKline, which is testing adjuvants with proteins; the Netherlands-based biopharmaceutical company Crucell, collaborating with Harvard University to develop novel adenovirus vector-based vaccines; Pennsylvania-based Inovio, which is creating a vaccine that contains viral DNA plus a cytokine; Maryland-based Profectus, which is creating DNA, protein and vesicular stomatitis virus-vectored vaccines; and Novartis, which is developing adjuvanted protein vaccines as well as viral vectors. The European company Mymetics is working on virosomes displaying gp41-derived proteins as a mucosal vaccine. Aventis-Pasteur, in collaboration with Eurovac, a European vaccine consortium, is developing additional live poxviral vectors to be used with protein boosts from Novartis.
Of course, many challenges remain. Thanks to the President’s Emergency Plan for AIDS Relief (PEPFAR), and other donors, HIV treatment has become a reality for more than six million adults and children in developing countries; yet in 2012, fewer than half of those living with HIV who require treatment are receiving therapy. In only an estimated 28% of people living with HIV in the U.S. has suppression of HIV RNA been achieved; such suppression is a marker of treatment success and a sign of the transmission risk.
The oral medications used today to treat individuals who are HIV-positive work very well, and life expectancy for this population is close to normal. Having said this, we still need to be cognizant of the high cost and frequent side effects from taking these drugs. Second, oral medication can also be used to prevent infection, but again the cost is considerable—up to $12,000 per year—and compliance will continue to be a challenge. Vaccines for prevention have begun to show a benefit and will materialize first, but clinics are also interested in the potential for therapeutic vaccines to be used with the oral medication in HIV-positive individuals. Here the anticipation is that the virus could be eliminated, or could at least result in improved control.
Regarding the issue of funding for research, the National Institutes of Health (NIH), and in particular NIAID, are to be commended for their commitment to finding a vaccine solution to HIV/AIDS. The recent award of $186 million over seven years for basic research and vaccine development to the Center for HIV/AIDS Vaccine Immunology (CHAVI), based at Duke University, attests to the dedication of the NIH for HIV vaccine development. Basic research funds have also recently been slated for Emory University and the Scripps Research Institute in an effort to further understand antibody and T-cell antiviral function. The federal government’s broad-based approach to finding a solution or combination of solutions to the HIV epidemic is encouraging. Having said this, there are reasons why smaller biotechs with tighter budgets might find funding difficult—not least of which is the poor record of companies that have failed in their attempts to create a viable vaccine. Another reason is the length of time required until a licensing event occurs; many investors would rather not wait that long.
Furthermore, there is the ongoing challenge of maintaining expanded access to, and coverage of, high-quality prevention and treatment services tailored to affected populations; these are critical to keeping people living with HIV healthy and to dramatically lowering the number of new HIV infections.
In short, as we ponder the progress that has been made in developing an HIV/AIDS vaccine and look to the future advancements of these efforts, we have cause for optimism. The AIDS vaccine field has generated evidence for the ability of vaccines to prevent HIV infection in humans, and there is hope that the low levels of prevention achieved thus far can be enhanced by regular boosting. The field has also developed new nonhuman primate models for testing vaccines, enabling researchers to clearly distinguish the ability of prototype simian vaccines to prevent infection. I am confident vaccines will conquer the AIDS pandemic. Tremendous progress has been and is continuing to be made.