Blue Genes – Science news

Posted by: colinhockings

When HIV was discovered as the causative agent of AIDS in 1984 (and has since been repeatedly proven, despite denialists claims – see Ben’s post) scientists were relieved: “It’s a virus! Phew, viruses are something we can deal with. Alright, somebody go cook up a vaccine: problem solved”. According to wikipedia, senior figures in the US health system claimed that a vaccine would be ready in as little as two years. 25 years later HIV is getting the better of us like no other disease, and the vaccine front has seen failure after failure. It seemed to me that it was truly impossible to build a vaccine against HIV and our only hope would be some form of procedure where T cells are removed from the patient, ‘cured’ of HIV (not quite as easy as it sounds, surprisingly enough) and reimplanted into irradiated patients – or something similarly novel (read: impossible and/or impractical). Imagine my surprise then when I finished work to find a BBC article saying that an HIV vaccine had ‘reduced infection’, and after a little bit of surfing I check Twitter to see that ‘HIV’ is trending. Even the Huffington Post had some (relatively) positive things to say.

So what’s all the fuss about? It’s hard to give much detail because the study – beautifully named RV144 – hasn’t yet been published (as far as I can tell, and I’ve looked pretty hard [Update: see footnotes]). There’s several press releases around, from all the various organisations that were involved, including:

• MHRP (U.S. Military HIV Research Program)
• UNAIDS (Joint United Nations Programme on HIV/AIDS)
• NIAID (National Institute of Allergy and Infections Disease)

The study had two (blinded) groups, one control group (receiving placebo injections) and one experimental group (receiving four ‘prime’ doses of ALVAC HIV and two boost doses of AIDSVAX gp120 B/E), with over 8,000 volunteers in each group, lasting from 2003 until now. AIDSVAX has been tested before, but showed no effect, and the ALVAC has only been evaluated for safety. The researchers were quite careful to make the study as ethical as possible, giving lots of good safe sex advice and promising free medication to anyone who contracted HIV during the course of the study (as well as testing the participants for HIV every six months). The impact this has on the infection rate is clear to see in the results: 74 people in the control group and 51 vaccinated volunteers caught HIV – in a country where approximately 1 in 100 people is HIV positive. Before you say ‘well that’s a tiny difference’, remember that there were 16,402 people, which gives the study a fair amount of power. One would, however, need to take a look at the original data to be sure that the statistical significance is really significant. On a side note, I get really annoyed at studies that are released to the press before anyone is allowed to check the data. In this case it’s a large, well-known, highly-anticipated trial run by several reputable institutions so I’m sure their methodology isn’t intentionally dodgy, but it’s still very bad scientific practice.

I found an interesting 2004 release from TAG, the Treatment Action Group, which campaigns ‘for larger and more efficient research efforts…towards finding a cure for AIDS’, saying that the Thailand trial (called RV144) is flawed for several reasons.

• A single experimental arm won’t allow the relative effects of the two vaccines to be tested. At the time, there had been no clinical trials of ALVAC vCP1521 efficacy and I don’t think that that has changed since then. If it’s still true then they have a very valid point: the experimenters cannot tell how much of the effect is from the ALVAC vaccine alone. TAG also had some concerns that the AIDSVAX gp120 boost may neutralise the other vaccine, based on experiments in macaque monkeys. It is therefore quite possible that ALVAC vCP1521 worked much better, but we won’t know until another large trial is completed.
• TAG also questioned the ethics of recruiting volunteers – who mostly claimed altruism as their motivation for joining – to a trial that would, at best, lead only to further trials (based on the arguments above).

The reason why such a large trial was performed that won’t actually answer any questions is fairly stupid. It was planned well before two clinical trials for AIDSVAX came back negative, and a trial for the ALVAC vaccine (called HVTN 501) was cancelled. Despite the drastically changed circumstances, RV144 went ahead, leaving us with tantalising evidence that we’re making progress, but not really changing the game much.

On the bright side,  at least we have proof that HIV isn’t invincible. This study follows hot on the heels of the first case of a man cured of HIV (published in February 2009), so I think the entire AIDS research field is looking a little more optimistic. While the number of HIV positive people in the world is still increasing, I think it’s fair to say that we have good cause to be hopeful.

***Update***

Martin Robbins of the Lay Scientist is not so impressed. Apparently the results are only barely significant (p = 0.048 i.e. there is a 4.8% chance that the difference between the groups is down to random fluctuation)

ERV has an interesting description of thesoft of immunological reaction they were trying to elicit with the Prime-Boost strategy

***Update***

Katie Stover (Media Representative for NIAID) told me that the study will probably be published in October, in NEJM, to roughly coincide with the AIDS Vaccine conference in Paris