Through its six days of presentations for 19,000 attendees, hundreds of seminars and more than 4,000 scientific "posters' examining every aspect of AIDS, the single message that stands out from the XVIII International AIDS Conference, which ended in Vienna last week, is the cumulative progress on every front---prevention, treatment, basic science and human rights. Changes in human behavior once considered unlikely, from condom use to adult circumcision (which halves men's risk of contracting HIV heterosexually), are now so widespread that in 21 of 25 of African nations where AIDS is worst, infection rates of young adults have fallen by 25% or more. Key government policies are changing so fundamentally that a list of nations---including Vietnam, China, and the Ukraine---which utterly derided drug treatment as coddling addicts are beginning the treatment programs that will lower both their HIV and addiction rates. The antiretroviral medications (ARVs) which, in the past decade, came into wide use as the first effective AIDS treatment have turned out to have an unexpected bonus; their ability to suppress the virus to very low levels not only increases lifespan, but slash the prospects that a person with HIV/AIDS will transmit the virus sexually. In studies of heterosexual couples, for example, where one partner is HIV+ and the other is not, ARV use by the partner with HIV/AIDS appears to offer better protection to the partner who does not have HIV than condoms. No doubt this is partly because people sometimes "forget" to use condoms, but it is still a very important finding.
What is so striking about this progress is that it is not the result of one "breakthrough"---like the preventive vaccine which has always been the Holy Grail of AIDS research---but the cumulative effort of years of work and worry across the globe. From sophisticated scientific labs to volunteer educators promoting prevention on frontlines from African villages to the South Bronx, the AIDS effort has become a fascinating world-wide effort. With its increasing integration of science, government policy and impressive, local community programs, along with activists constantly pushing to propel progress, it forms a radical new and important model for fighting disease. We are left, therefore, to consider a radical idea. The idea that AIDS may never be conquered until there is a vaccine is natural and compelling in an infectious epidemic. But, with the scantest of progress to show in two decades----proponents, themselves, concede that a preventive vaccine is still unlikely to appear for another decade or more---this slow search remains the great devourer of research dollars from governments and foundations alike.
Yet, as we wait and wait again, all the other progress starts to add up to seeing AIDS contained and controlled on a level that was not thought to be possible absent a preventive vaccine. Potentially, with treatment science now in the wings, we can have better, cheaper treatments that, even in an era of reduced budgets, reach more people and also constantly slash transmission and the rate of new HIV infection.
Let's briefly summarize the state of treatment. ARVs were more than a welcome advance; they gave millions of people their lives back. Nonetheless, their expense and the fact that these chemotherapy agents have to be taken every day for life make them a partial remedy. Despite billions in international donations, mainly from the United States, and cheaper, generic versions of ARVs being largely used in the developing world, only some 5 million of the estimated 30 million people worldwide who need ARVs can now obtain them. In the United States, itself, funding problems have left more than 1,700 HIV-positive people on long "waiting lists" for ARVs. Painful side effects make them unusable for some and, over time, they simply stop working for a significant portion of people.
At the Conference, however, activists and community groups highlighted another direction for treatment progress--- immune-based therapies. Unlike ARVs, which directly attack the virus, immune-based therapies variously bolster the patient's own immune system to fight HIV. The leading candidates, known as a therapeutic vaccines---or vaccines designed to boost the immune systems of people who already have an illness----would perhaps be given once or twice a year, a regimen that markedly lowers costs from the lifelong daily regimen of ARVs, while making treatment easier and feasible for millions more people. They, too, are not likely to be a cure, but their goal is long term suppression of the virus to the point that patients won't need other treatment for years. Bolstering the immune system, moreover, so far appears to bypass the serious side effects of ARVs.
Yet, therapeutic vaccines have been the stepchildren of research attention and funding; progress here has been made mainly by smaller biotechnology companies. "Therapeutic vaccines and drugs that stop the HIV-induced hyperactivation of the immune system are our best chance," states David Miller, a nonstop and highly knowledgeable Bronx treatment activist. "But the National Institutes of Health isn't putting money into this. They just keep studying old drugs."
Although therapies that look good in the laboratory---and even in their first trials with small numbers of patients---often fail to prove their promise in larger patient trials, an attraction of immune-based therapies that they present multiple approaches that show promise. A National Association of People with AIDS forum, co-sponsored with The AIDS Institute at the International Conference, suggested the range of innovative immune-based therapies now appearing. Treatments presented in early research stages included the success of Immunacia, an American-Hungarian-Italian biotech, with a new class of drugs known as AV-HALTs, which reduce both HIV levels and the over-activation of the immune system that is so destructive to people with HIV; VIRxSYS Corporation's gene-modified cellular therapy, which modifies the patient's own immune cells to make a personal "mini-vaccine" that combats the virus in patients for whom ARVs no longer work; the combined approach of an unique topical nano-medicine which reduces HIV by 70% after four skin applications with a "booster" therapeutic vaccine also from Immunacia; FIT Biotech's novel DNA vaccine and Receptopharm's Pepteron, which stimulates the immune system to inhibit HIV replication.
Most important, two therapeutic vaccines also presented have reached the critical point of being evaluated in larger clinical trials that will not only give substantial answers about their utility for wide use, but mark a key step in moving the field of immune-based therapy out of stepchild status. One is Vacc-4x, a peptide-based vaccine made by Bionor Pharma, a Norwegian company. In a trial concluded two years ago with 40 patients, the vaccine suppressed HIV for an average of 31 months---and, in a few patients, for up to seven years. Moving forward, by the end of the year, Bionor will present results from the first ever large "double-blind placebo controlled" study that directly compares outcomes for HIV patients for whom therapeutic vaccine is used to "replace" ARVs to those given a placebo while also halting ARV use. Those results may take therapeutic vaccines to a turning point.
Argos Therapeutics, an American company, meanwhile, is just launching the first multi-center trial of a vaccine that uses dendritic cells, the "entrance" cells of the immune system, from patients to customize a vaccine to them.
Steadily, and step by step, science is advancing the hope for therapies that are safer and more accessible for patients even as they suppress the virus to levels that could be expected to provide the "extra" benefit of slashing the sexual transmission of HIV. But, will we advance? Only two of these promising immune-based therapies have ever received funding from the National Institutes of Health to assist their development or clinical trials---a contrast to the by now multi-millions and constant star attention that preventive vaccine development has claimed from foundations and government institutes alike; a preventive vaccine is considered the "real" vaccine---the great thing that scientists crave to discover and the "breakthrough" that funders want credit for funding. Yet, the lesson of AIDS, with its complex and unique challenges, lies elsewhere---that cumulative, steady progress will ultimately become its own "breakthrough."
In this vein, an international group of researchers, writing in Science Magazine, recently underscored that sustained work to develop therapeutic vaccines could both advance knowledge for the ultimate development of a preventive vaccine---while providing an arena where it is easier, faster--- and incredibly less expensive---to test strategies and results. "Proper incentives and programs should be put in place to recruit the broad and multidisciplinary scientific research community that will be indispensible to succeed in this endeavor," they urged.
That's the scientific way of saying money should go towards immune based research now.
Yes, it's sad that despite the years of research and millions of dollars spent, there's no AIDS cure and there's no preventive vaccine; but saddest yet would be to ignore the real possibility for real control of AIDS in the foreseeable future. When immune-based therapies prove themselves to a point that they go into production---a process that will be aided by the fact that some of these products are genuinely cheap to produce within the usual costs for sophisticated biologic agents---the worldwide network, unique to AIDS, will get right to work. The scrappy local programs and irrepressible volunteers in country after country, who so advanced prevention and distributed all the ARVs they could scrounge, the people ready and waiting to take the advances of science to huts and the streets alike, will see that millions still left out benefit---and benefit fast.
Notes: The author is on the Community Advisory Board (an unpaid position) of Bionor Pharma, one of the companies mentioned. Those interested in a comprehensive overview of the state of AIDS research, from diagnostics to treatments to vaccines, may wish to consult the Treatment Action Group's important guide, the "TAG 2010 Pipeline Report."
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