HIV/AIDS Experts and Advocates Say Research Should Focus on a Cure

Effective combination antiretroviral therapy has dramatically reduced rates of illness and death among people with HIV, but it does not cure the disease. Recent research presented at the 16th Conference on Retroviruses and Opportunistic Infections (CROI 2009) last month in Montreal showed that even though today's best antiretroviral drugs can completely suppress viral replication, HIV remains in the body in resting CD4 T-cells and probably also in another as-yet unidentified "reservoir."

Now that the hurdle of viral suppression has been overcome, HIV/AIDS researchers and advocates are turning their sights toward finding an actual cure. This goal was discussed in an article in the March 6, 2009, issue of Science by Douglas Richman (University of California at San Diego), David Margolis (University of North Carolina at Chapel Hill), Warner Greene (Gladstone Institute of Virology and Immunology), Daria Hazuda (Merck), Roger Pomerantz (Tibotec/Johnson & Johnson), and Project Inform founder Martin Delaney, who recently passed away after a battle with hepatitis B-related liver cancer.

Laying out the challenge, the authors noted that despite its success, "chronic suppressive [antiretroviral] therapy is limited by its cost, the requirement of lifelong adherence, and the unknown effects of long-term treatment." Furthermore, research increasingly suggests that even low-level HIV viremia may have previously unrecognized deleterious consequences such as cardiovascular disease, cancer, cellular aging, and premature neurocognitive decline.

Despite the very low rates of toxicity of many of the newer HAART regimens, the authors continued, "[e]ven modest toxicities may have cumulative effects over decades of treatment." Finally, they added, "the cost of HAART may be too much to sustain treatments on a global scale, as millions are affected."

The idea of HIV eradication was proposed in the mid-1990s, around the time the development of protease inhibitors enabled effective combination therapy. The "hit early, hit hard" theory attributed to David Ho -- Time magazine's Man of the Year in 1996 -- suggested that starting treatment very early in the course of infection with powerful drugs could completely rid the body of HIV.

This goal was put to the side after studies showed that even very early therapy did not seem to eradicate the virus, and people taking the new drugs began to experience unexpected long-term side effects, leading many clinicians and patients to prefer deferring therapy until absolutely necessary.

The Science article called for a collaboration between academic researchers, clinicians, the pharmaceutical industry, and community advocates in a public-private partnership. While the National Institutes of Health currently provides funding to specific investigators working on eradication, to date there has been no concerted cooperative effort.

Such a "collaboratory" would involve sharing data and resources in a common effort to find the elusive permanent cure that could eliminate the need for lifelong therapy. The Treatment Action Group also recently called on researchers to devote more attention to a cure.

One of the most difficult aspects of eliminating the virus is finding a way to activate latent cells harboring HIV -- releasing the virus to render it susceptible to existing antiretroviral drugs -- without activating all uninfected latent cells; to date, several initially promising attempt in this area have not proven effective.

"Years of effort have led to public health strategies to reduce the risk of cancer, a vaccine that prevents cervical cancer, better therapies to treat malignancies, and curative therapies for some cancers," the authors noted as a potential model. "Such a multifaceted approach should also be applied to the effort to cure HIV infection. This will require behavioral and biological tools to prevent HIV infection; safe, affordable, and nontoxic therapies for initial control of HIV infection; and new interventions that can achieve a drug-free remission of viremia in some patients."

3/20/09

Reference

D Richman, DM Margolis, M Delaney, and others. The challenge of finding a cure for HIV infection. Science 323(5919): 1304-1307. March 6, 2009.