Miranda Smith
Don’t believe the hype: Gammora is not an HIV cure
With the internet and a twitter account, spreading information is easy. When it comes to HIV cure research, it can be hard to distinguish genuine, good quality science from spin-doctored, over-hyped attention seeking.
The story of ‘Gammora’ is a cautionary tale.
Flood of false claims
Towards the end of October, an Israeli company, Zion Medical, issued a press release. The press release described the results of a small phase 1/2a human clinical trial of their peptide-based compound ‘Gammora’.
They claimed that Gammora eliminated up to 99% of HIV within four weeks and has the potential to cure HIV infected patients.
Treatment for HIV involves the use of antivirals that stop the virus from replicating. But here’s the catch! Current antivirals can’t eliminate the virus that goes in to hiding and persists indefinitely. We call this the HIV reservoir and at the moment, we have no way to reduce this reservoir. It is unclear whether Gammora is acting as an antiviral or is tackling the reservoir – hence the significant confusion in the publicity around the drug.
Unpacking the press release
The press release does not contain any scientific data. It offers statements such as ‘Most patients showed a significant reduction of the viral load of up to 90% from the baseline during the first four weeks’. If we’re looking for an HIV cure, the critical issue is whether there’s a reduction in the HIV reservoir. The press release does not say if the study even looked at the HIV reservoir. Viral load is usually measured in the blood plasma – the liquid part of blood. Regular antiviral therapy should reduce the viral load in plasma.
There were only a small number of study participants, and almost no information provided about them. We don’t know if the participants were male or female, or how long they had been infected with HIV. We don’t know what previous treatments they had received (or for how long), what their immune status was or how old they were.
Details of the trial design are also sketchy. We don’t know whether the participants were already receiving antiviral therapy. The details of how, and how much, Gammora was administered is also unclear.
In part two of the study, participants received antiviral therapy either with or without Gammora for a short 4-5 weeks. This detail in itself is concerning since some study participants were only receiving a single antiviral agent, not the gold standard triple therapy. The press release claims that ‘combined-treated patients demonstrated sustained viral suppression and achieved HIV-1 RNA <300 copies/mL, and showed up to 99% reduction in viral load from baseline within four weeks’. Let’s unpack this.
Firstly, measuring virus in the plasma doesn’t address the HIV reservoir. Most people with HIV who start antiviral therapy will end up with undetectable virus in their plasma. The problem for achieving an HIV cure is that in infected individuals on HIV treatment, there is still virus inside cells in blood and tissue. This residual virus is not measured in plasma by routine assays. There are no details on the HIV reservoir in the Gammora press release.
Secondly, the press release makes no mention of what happened in the group who only received the antiviral treatment, so we can’t compare the two groups. Perhaps the antiviral group showed similar results to the group that received Gammora?
The total study period of about 10 weeks is hardly ‘sustained’ for a chronic infection that can last years.
Finally, the ‘99% reduction’ claim for viral load from baseline suggests that the study participants were not on therapy at the beginning. These sorts of reductions are usual when someone starts therapy for the first time.
The trial was not registered in any clinical trial registry. This means that there is no publicly available details of the study design or recruitment criteria.
What about the back story?
Let’s take a step back and look at the preclinical data that the trial was based on.
There is a (peer reviewed) article which refers to the early development of what is now ‘Gammora’. The early experiments were done in a human cell line called ‘H9’ that was infected with ‘wild type HIV’. The authors do not list where this virus came from or what clade or subtype it belonged to. They also don’t clearly display their results. This makes it difficult to view the difference between cells exposed to the various experimental conditions. The paper is vague and lacks many important details.
There is some evidence that the peptide mix (now ‘Gammora’) has an impact on the number of infected cells. Even the authors admit, however, that they did not look for latently infected cells. The authors state that ‘the novel approach described here for AIDS therapy is only in its initial steps and further attempts to improve the activity of the stimulating peptides are currently conducted in our laboratory’. Published in 2010, we found no further related publications. The published study has been cited four times. There is no evidence that the strategy has been replicated by other research groups.
What now?
Peer reviewed publication of the ‘Gammora’ clinical trial data will be the best format to review the effects. A press release scattered with catchphrases is misleading and definitely not a way to communicate scientific advances.
What does all this tell us? Gammora is not a cure for HIV.
For more on interpreting media reports of HIV cure, read our article on sorting fact from fiction.
For further commentary on the Gammora drama, see here, here and here.
.png)