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Ending the AIDS epidemic

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The scientific options for vanquishing HIV are looking better. The prospects for paying for them may be getting worse.

Thirty-one years into the HIV epidemic, health authorities are finally starting to sound hopeful about the prospects for curbing it.

If that sentence sounds bitter or sarcastic, it isn't meant to be. Rather, it's an honest assessment of how long and frequently depressing the era of HIV and AIDS has been, and of how much misery it has spawned. But it also acknowledges reasons to think that maybe, just maybe that's beginning to change.

Progress of any kind against HIV has been hard won. For the first 15 years or so after the recognition of AIDS in 1981, a positive diagnosis for its virus was practically a death warrant. Campaigns for safe sex, sterile needle exchanges, and other measures for curbing transmission helped. The introduction of antiretroviral drug treatments in 1996 gradually helped to change HIV infection from a way-station diagnosis en route to full AIDS into a much more manageable chronic condition.

Even so, the state of the epidemic was extremely bad: too many people were infected, particularly in parts of the world that could ill afford expensive medical treatments; too many people disregarded advice about safe sex; too many people who were at risk even investigated their HIV status. Worst of all, the remedy that everyone wanted and that U.S. Health and Human Services Secretary Margaret Heckler had promised back in 1984 might be imminent -- an effective anti-HIV vaccine -- was elusive.

Nevertheless, this week, as 25,0000 scientists, policy makers, activists, and others gather in Washington, D.C., for the 19th International AIDS Conference, many are finding encouragement in recent scientific and clinical developments that suggest it might be possible to win the war against AIDS. The optimism shines in the Washington D.C. Declaration issued by AIDS activists in advance of the conference, which reads in part: "Through new scientific advances and societal, political and human rights gains, it is possible to turn the tide against the AIDS and begin to end the epidemic in our lifetimes." It is front and center in a New England Journal of Medicine (NEJM) essay by Diane Havlir, M.D., and Chris Beyrer, M.D., M.P.H. from last week cautiously titled, "The Beginning of the End of AIDS?"

That question mark is not merely a rhetorical hedge. That victory is possible but not definite, and not even probable without stepped-up coordinated international efforts and a lot more money.

AIDS then and now

A look at how the HIV/AIDS epidemic has changed since the 1990 International AIDS Conference in San Francisco, which was the last time that it was last held in the U.S., is instructive about how much worse the problem has become -- but also about why there is some cause for hope.

Particles of HIV (green) bud from a cultured white blood cell (blue) in this electron micrograph. (Credit: CDC/ C. Goldsmith, P. Feorino, E. L. Palmer, W. R. McManus)

(Incidentally, these meetings were initially held in the U.S. every other year, until the U.S. Senate made that effectively impossible in 1987 by banning HIV+ people from entering the country even for short times, and even for such purposes. That ban was lifted by President Obama two years ago. The return of the conferences is itself a mark of progress in that it improves the visibility of the issue in the Capitol.)

In 1990, the total number of cases of AIDS reported to the World Health Organization (WHO) was 307,000, but the true number of cases was estimated to be close to a million. Eight-to-10 million people were believed to be infected with HIV.

Today, according to the most recent report issued by UNAIDS (pdf), 34.2 million people are infected with HIV. More than 22 million of them are in sub-Saharan Africa. More than 60 percent of new infections occur among men having sex with other men, but globally, women between the ages of 15 and 24 are the group most at risk for contracting HIV. Only half of those who should be getting treatment are.

In the U.S. alone, 1.1 million people in the U.S. have HIV, and roughly a fifth of them don't know it, according to the Kaiser Foundation. Only 28 percent of Americans with HIV are suppressing the virus with antiretroviral drugs: most of the infected people are either avoiding or missing out on treatment, or are oblivious to their HIV status.

Out of about 60 million people worldwide who have been infected with HIV over the past three decades, more than 30 million of them have been killed by AIDS. (The AIDS death toll among Americans stood at 642,000 in 2009.)

Treatment works

Horrific as the statistics are, they harbor a particle of good news. The annual death toll from AIDS peaked in 2005 at 2.3 million. As of 2011, it had fallen to 1.7 million.

Part of the credit for that improvement belongs to behavioral prevention efforts, which have helped to slow the rate of growth in the numbers of the infected. Yet a bigger share goes to the use of antiretroviral drugs, which slow the progression of the disease and reduce HIV's ability to spread.

That improvement comes with a big price tag. Antiviral treatments in the U.S. can cost $12,000 a year, but poor countries can typically buy the drugs at a steep humanitarian discount.

Nevertheless, the world now spends $17 billion annually on HIV prevention and treatment in the developing world. Health authorities aim to raise the number of people there on antiretrovirals from eight million to 15 million by 2015, which could help to slash the death rate further. Doing so will reportedly require an extra $7 billion annually.

More reasons for more drugs

The argument for making anti-HIV drugs more widely available has only grown stronger with recent research news. Two weeks ago in the NEJM, Jared M. Baeten of the University of Washington and 44 co-authors presented evidence that if uninfected heterosexual men and women who had infected partners took daily doses of a combination of antiretrovirals (marketed as Truvada by Gilead Pharmaceuticals), they could cut their risk of HIV infection by 90 percent. This approach to prevention, called pre-exposure prophylaxis (PrEP), was previously tested and found effective among homosexual men by Robert M. Grant of the University of California, San Francisco, and his colleagues, as described in a 2010 NEJM paper: it found that PrEP lowered their risk by 44 percent.

Such levels of protection are far from sufficient over the long run, but as supplements to safe sex -- or fallback measures in situations where using condoms or abstaining aren't feasible -- they can have a huge impact on the spread of HIV.

Truvada has side effects (such as nausea) but they are generally deemed minor. A year's worth of the pills costs about $14,000 in the U.S. Gilead has not yet commented on suggestions that it should cut the price to $100 per year in needy countries.

Arguments for using PrEP to fight HIV have met with opposition on several grounds in the past. One is that some people might take false confidence from the drugs and start engaging in riskier sexual behaviors. Another is that use of the drugs by the uninfected might lead to more drug-resistant strains of HIV. For years, WHO and other authorities have therefore recommended holding off on administering such drugs until the concentration of CD4+ T-cells in an HIV patient's blood fell below 350 per microliter.

Those concerns now seem to be giving way. This past Thursday, on the heels of the recent research findings, WHO announced its endorsement of PrEP as an anti-HIV strategy. And one of the first pieces of news to emerge from the International AIDS Conference on Sunday was a statement by Melanie Thomson, speaking for the International Antiviral Society-USA, that it was recommending that everyone start treatments with antivirals as soon as they knew they were infected.

Vaccines and more

The best long-term hope for prevention still lies with the development of an anti-HIV vaccine. Doing so has turned out to be phenomenally, perversely difficult for many reasons, not least that HIV mutates so rapidly that its shifting antigenic profile is a slippery target for antibodies. Most anti-HIV vaccine candidates over the past three decades have been dismal failures; in at least one case, a vaccine trial was canceled because it seemed to increase some men's susceptibility to the virus.

An important turning point, however, was a 2009 trial in Thailand of RV144, a combination of vaccines that had previously proved disappointing on their own. As the Ministry of Public Health–Thai AIDS Vaccine Evaluation Group reported in NEJM, the RV144 compound reduced infections by about 30 percent -- too low to be a satisfactory preventative but an important (and highly welcome) validation of vaccines' relevance. Follow-up studies are now in progress, and the clues gathered from the RV144 trial are helping to guide the development of other new vaccine candidates.

Sunday at the International AIDS Conference, according to published reports, Nelson Michael, director of the U.S. Military HIV Research Program at the Walter Reed Army Institute of Research, who led the RV144 trial, speculated that large-scale studies of some of the new vaccines' effectiveness might begin in four years, after further clinical safety trials, and that the first practical vaccine might be ready for licensing by 2019. Such a vaccine might still only be about 50 percent effective.

The price of progress

Encouraging research progress does not always need to display immediate clinical results. Another important but lower key research announcement was made last week in the pages of Science Translational Medicine by Timothy M. Dudek of Massachusetts General Hospital and his colleagues. They succeeded in creating a better, more "human" mouse for the laboratory study of HIV. Chimeric mice engineered to have human immune-system cells have been used in HIV research for some time (because HIV will not infect mouse tissue). These new mice, however, have human cells infiltrating a wide variety of their tissues. Because of this more human milieu, the researchers say, the mice's immune responses to HIV are closer to those seen in infected humans. The animals should be able to help HIV researchers study how humans -- maybe even individual humans with particular genomic characteristics -- try to fight off HIV.

Expect more encouraging research news to emerge from the AIDS conference all week. And watch for other creative approaches to improving public awareness of HIV, such as the program in Washington that allows people visiting the Department of Motor Vehicles to get tested for HIV for just $7.

The dark cloud overhanging all these ideas, however, is the worry that public funding for HIV/AIDS research, prevention, and treatment won't keep up with the demands of either the scientific possibilities or the humanitarian priorities. International AIDS funding has essentially been frozen for the past four years. The mismatch between the allocated global resources and the scientific options is getting worse, not better.

As Havlir and Beyrir noted in their NEJM essay:

The global fiscal realities are compounded by what we would argue are artificial debates that pit AIDS against other global health needs. We believe that the yield on investment in HIV research and care is unparalleled in modern medicine. ... Comprehensive economic models predict that making the needed investments in HIV-related efforts will result in cost savings over the long term. It would be an extraordinary failure of global will and conscience if financial constraints and false dichotomies truncated our ability to begin to end AIDS just when the science is showing that this goal is achievable.

Top image: International AIDS quilt in Washington, D.C., in 2004. (Credit: Elvert Barnes/Flickr)

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John Rennie

Contributing Editor

Columnist, Science John Rennie is the former editor-in-chief of Scientific American. He has written for IEEE Spectrum, New York Times and The Economist and has appeared on the History Channel, Discovery Channel, NPR and Minnesota Public Radio. He has spoken at the World Business Forum, Massachusetts Institute of Technology, Wharton School of Business, University of Tennessee and Middlebury College and is an adjunct instructor at New York University, editor at large for Txchnologist.com and contributing editor to ecomagination.com. He is based in New York. Follow him on Twitter. Disclosure