October 2009 Archives

For the next few days at least- and hopefully longer- I will be in a New York groove. No, I won't be in the City, but following the Yankees playoff drive.  Game 1: CC is a horse, Jeter is a stud, A Rod has chased away his ghosts, and the Yankees lead the series 1-0. 

In HIV land, you might have seen this story from the fine folks across the hall in the aidsmeds.com cubicles about the early closure of a phase III trial of apricitabine (ATC). Apricitabine is an NRTI, like AZT or tenofovir- that was being tested in people whose HIV had developed resistance to 3TC or FTC. 

Avexa, the company developing apriciabine, released a cryptic (a-vexing?) press release saying that the study, meant to be 48 weeks, was being closed early in order to 'offer key insight into ATC's role in the overall HIV treatment landscape, and discussions with regulatory authorities may clarify the ATC approval path. Secondly, this will allow for a mature enough data point to enable potential partners the ability to make a definitive decision on licensing of ATC'

I have no insider scuttlebutt on this story, but it doesn't sound good. The development of this drug has been slow and meandering. The studies done to date have shown some efficacy, but nothing really special. 

The Avexa press release, while not really telling us anything, suggests to me that this drug is dead in the water. Typically when companies have positive news they share it. This is even more true of smaller companies, who are dependent on investors.

The need for such a drug is questionable as well. On one hand, many (most?) people's HIV will develop resistance to FTC or 3TC. These drugs are part of most HIV regimens and a single point mutation- called M184V- is enough to greatly reduce the virus' susceptibility to the drugs. However, some research- including a study presented at the recent ICAAC conference, shows that people seem to do just fine clinically if they keep taking these drugs after that resistance mutation emerges. 

The bigger picture question for me is the need for NRTIs. NRTIs- the first class of HIV drugs developed and still the 'backbone' of the vast majority of HAART regimens- don't match up favorably when compared to the rest of the anti-HIV armementarium. They are relatively weak and toxic and their place in the 'HIV treatment landscape' is largely an accident of history- that is it has more to do with when the drugs were developed than any strong research. 

This should not be read as 'stop taking your NRTIs.' While I have doubts about this entire class of drugs, there simply aren't enough data yet to adequately understand the role they play, or more accurately should play in HIV treatment. 

As we wait for more data- Go Yankees!

After I hit save word came down the proverbial wire that the FDA has voted to approve Selzentry (maraviroc) for people taking HIV drugs for the first time. Stay tuned for more info. 

I admit it it. My first reaction to this story was, 'told ya so!' My second reaction wasn't much more evolved- something along the lines of 'duh!' Eventually I was able to access a deeper part of my humanity and feel genuine disappointment that the vaccine breakthrough is even less than it appeared on first blush. 

To review: Almost 2 weeks ago, the mainstream press ran stories trumpeting the first ever successful HIV vaccine test results. The basic story was that researchers combined two failed vaccines, using a two step prime-boost method, and tested them in Thailand. It was a large, expensive, randomized, controlled trial- enrolling 16,000 people and following them for five years. 

The press release touted an approximately 1/3 reduction in the number of new infections among people in the vaccine arm, compared to those who received a dummy or placebo vaccine. If validated a vaccine with even this modest level of protection would indeed be a breakthrough.

I was initially skeptical for two reasons. First, the vaccines used in the study had failed in previous studies, and combining two ineffective vaccines seemed highly unlikely to result in a successful vaccine. The second reason is some of the people involved in this study, were with Vaxgen when they engaged in unethical data spinning, in a desperate attempt to secure more funding. 

So, I was not surprised when I read that another analysis of these data showed that the results failed to meet statistical significance, and that analysis was suppressed. This second analysis removed anyone from the calculations who did not strictly follow the study protocol. Analyzing the results this way amounts to a strength test for the original analysis- a vaccine that is truly protective, even modestly so should test out so in either way. 

The fact that it didn't and that the researchers chose not to share that analysis deepens my skepticism. 

And while I felt a bit of schadenfreude, I do feel an honest sense of disappointment. The HIV

 vaccine effort could really use some good news- a proverbial shot in the arm if you will forgive me. But this kind of data cooking is exactly not what is needed. Science relies on honesty, failed studies are often just as valuable as successful ones, when they deepen our understanding. A full, unbiased understanding of this, or any study might serve as something to build on. Nothing of meaning can be built on scientific dishonesty.