Tuesday, October 4, 2016

Publication by press release: When an HIV cure may not be a cure

I'm sure that many people have seen the news that a cure for HIV has been found; however, when you start digging into the claims, it is very clearly premature to declare this. It is true that a trial has begun to see if a chemotherapy drug, vorinostat, could be effective at helping the body to clear HIV with the aid of anti-retroviral therapy drugs. A total of 50 people are going to be in the trial and only one has completed treatment. The patient doesn't have HIV in their blood so the NIHR made a press release touting their "cure" and the media blew up with many sensational headlines. Once reporters had a chance to digest what was actually being said, calmer headlines have started to appear, including this excellent piece from BBC. I'll go through some of the finer points that need to be fully addressed before we can tout this a cure. 

The first is that they only tested this on people already undergoing HAART (highly active anti-retroviral treatment) treatment and had minimal detectable HIV titers. This hasn't really been tested in people with an active infection, only the integrated infection. The drug may not work in this scenario which would mean it's not a true cure. Looking further, the in vitro testing has only been done with latent infections and the drug does a good job of causing the latent virus to actively replicate. There is also no information on whether the virus can mutate so that this treatment is no longer effective. HIV mutation has been one of the main reasons that a cure for this virus has not been developed yet. Even the highly powerful CRISPR/Cas9 system was found to be susceptible to HIV mutation rendering it ineffective as tested.

A second major issue is that the people being treated continued with HAART while being treated with voinostat. This makes the results of the study difficult to interpret. HAART therapy causes the viral titers to be low as it interferes with the ability of the virus to replicate. Since they are measuring titer, they could potentially miss some latent infections (if this is indeed what they are doing; see the next point). 

The third major issue is that the trial is nowhere near complete. They have only recruited 39 out of 50 patients and the full results are not expected until 2018. This is a small pilot study that doesn't have the numbers to see how effective the treatment is, just if it can work or not. To be blunt, the press release was lean on specific measurements and methodologies, which is to be expected as it is not a paper but a press release. However, this makes it difficult to judge the way that the study was performed. 

A fourth issue is that only one person has completed the trial and they just finished. The researchers still need to test the patient for months to see if the therapy worked. Based on this and the previous three points, it is far too premature to call this a cure for HIV. The trend of publishing by press release is a growing trend that is not a welcome one. By issuing a press release, the normal peer review process is by passed, including post-publication peer review which is crucial to the process. Without the full methodologies or unbiased reporting of the results, there is no way for the scientific community to accurately judge the value of this work. In all fairness, I doubt the researchers had little say in the decision to give a press release. As it came from the funding agency, they likely seized on a promising report and used that to make the announcement.

Publication by press release is the bane of many researchers and has been of particular concern in HIV work. It seems that everyone rushing to cure this virus is using this method for disseminating findings. All too often, the sensational headlines announcing a particular technique as a cure do not live up to the hype that they have created. I'm sure that the drive to be the first to cure HIV is driving this. However, this is not based in the scientific method and it would be far better to have a solid cure that has gone through the rigors of the scientific method. Part of the reason for this is that every time a cure is announced, those suffering from this virus get their hopes up only to have them crushed yet again. To me, this is worse than just reporting that a treatment didn't work. The toll on people's health is real and this is not okay.

Update: A page called HIVforum.info shared the registration information on the clinical trial that includes some details about methods used in the trial. There still are questions, such as what method they are using to asses HIV DNA and if they are checking for integration beyond that or not, but this does give us more clues to what they are doing.