TAG HIV Basic Science, Vaccines, and Cure Project Blog

Provenge: An Approvable Therapeutic Vaccine?

The idea that vaccines might be used as therapies in some settings was first proposed by Robert Koch more than a century ago. But despite much study, there remains very little data suggesting any efficacy of vaccination against an established disease. The only approved uses of vaccines that might be considered vaguely therapeutic are rabies and smallpox when given very quickly after exposure  (for a great overview on therapeutic vaccination see this presentation by Mike Lederman). Now, according to recent releases from a company called Dendreon, it appears that the US Food and Drug Administration may be on the verge of approving a therapeutic vaccine for prostrate cancer called Provenge. To quote from yesterday's press release from Dendreon:

"Dendreon recently held a pre-BLA meeting with the FDA to review safety and efficacy data from its two completed Phase 3 clinical trials of PROVENGE, D9901 and D9902A, in men with asymptomatic, metastatic, advanced prostate cancer. In these discussions, the FDA agreed that the survival benefit observed in the D9901 study in conjunction with the supportive data obtained from study D9902A and the absence of significant toxicity in both studies is sufficient to serve as the clinical basis of a BLA submission for PROVENGE. As a result of that meeting, Dendreon recently announced plans to submit a BLA to the FDA in 2006 to market PROVENGE for the treatment of men with asymptomatic, metastatic, androgen-independent prostate cancer."

A BLA is a Biologics License Application, the equivalent of a New Drug Application or NDA for biological products like vaccines and cytokine therapies. While unfortunately this does not mean that therapeutic vaccines for HIV are right around the corner, it does offer some hope that the immune system can be prodded into exerting useful therapeutic effects and may address the most commonly cited reason for pessimism about prospects for therapeutic vaccines: the lack of an effective precedent .

Thanks to Daniel Raymond, Policy Director for the Harm Reduction Coalition and presider over the Hepatitis C Harm Reduction Project blog, for alerting me to this release.

AAV-based HIV Vaccine Moves Ahead

In TAG's recent pipeline report I wrote a little about an HIV vaccine candidate that uses Adeno-Associated Virus (AAV) as a vector. One of the unique features of this candidate is that it seems to persist and express the HIV antigens that it is carrying for months, at least in small animals and macaque monkeys, raising the possibility of giving just a single immunization. A phase I trial in humans was started back in 2002 in Germany and, although the data have yet to be presented, the trial's sponsor - the International AIDS Vaccine Initiative - announced yesterday that they are starting a phase II trial in South Africa. Hopefully, this is an indication that the vaccine is proving safe and immunogenic in humans. The new trial is the first phase II HIV vaccine study to take place in South Africa, it will enroll 78 men and women and last 18 months. The AAV vaccine to be used in the trial carries HIV antigens from subtype C, the most prevalent HIV subtype in southern and eastern Africa.

Cure Story Circulates

A story about a possibly "cured" individual from one of the UK's least reputable tabloids - The News of the World - is causing a bit of a stir. In typically crazed fashion (think Weekly World News), the paper uses the headline: " I'm the First in the World to be Cured of HIV." A young Scottish man, Andrew Stimpson, reportedly (and I'd stress that word) tested positive on an HIV antibody test in 2002 but has subsequently tested negative on three occasions since 2003. The story states that he developed symptoms of acute HIV infection in May 2002 and seroconverted in August. In October 2003 he was restested and the result was negative, which was confirmed by two further antibody tests. According to the article Stimpson's doctors at the Royal Chelsea and Westminster Hospital believe the tests were accurate. There aren't any details on viral load testing, just a single mention that he had "a low HIV count in his blood" after diagnosis. Stimpson says he just took a daily supplement regimen after learning of his status because antiretroviral therapy wasn't indicated. His initial reaction to learning of the negative tests was to threaten to sue the hospital, which seems to be how it emerged that the tests were accurate. It is perhaps worth noting that the hospital therefore also has a vested interest in claiming the test results were correct.

There seems to be a disagreement about the extent to which further research will be conducted on this case. The Chelsea & Westminster Hospital state that Stimpson has not returned for additional tests and make a plea for him to do so, while Stimpson gets quoted saying that he hopes he can contribute information that will help the search for a cure. Hopefully researchers will be able to analyze whether Stimpson developed HIV-specific T cell responses, since their presence would be further evidence that an exposure had occurred. Until further research is conducted this case remains an anecdote, and, unfortunately, one from a rather dubious source.

Ironically, in February of this year at the Retrovirus Conference a group of reputable Israeli researchers presented a poster abstract about an individual who has repeatedly tested negative (for both antibodies and viral RNA) after ceasing antiretroviral therapy some time ago. This case has received no media attention that I'm aware of.

UPDATE 11/14: "Man who says he beat HIV goes to ground." This Sydney Morning Herald article is based on a longer piece in today's Guardian. It appears that the story is unraveling:

"Campaigners are annoyed that having not yet undergone the vital tests, Mr Stimpson nevertheless signed contracts with the News of The World and the Mail on Sunday, both of which published his claims yesterday.

They also sounded a note of caution, noting that disclosures in his case arose not from medical research or peer review but from legal correspondence relating to an action Mr Stimpson was pursuing against the health trust. He had feared the positive results might have been wrong and had sought compensation. The trust's contention that both sets of blood tests were accurate emerged as it tried to defend itself from litigation."

UPDATE 11/16: And finally, the denouement: "Miracle HIV patient didn't have virus." The story includes this tortured quote from the Chelsea & Westminster Hospital: "It is probably there was never any evidence of him having the HIV virus," the Chelsea and Westminster NHS Trust admitted. "We don't know exactly what happened."