One intriguing area of research is the SAV001 vaccine, which is being investigated by Dr Chil-Yong Kang at the University of Western Ontario’s Schulich School of Medicine & Dentistry. Its phase I clinical trials (the first screens for safety of treatment) were completed in August 2013. The vaccine uses a modified version of the virus that has been ‘killed’, which then attacks cells infected with HIV – a similar approach to that used in the polio vaccine, among others. How promising does Barré-Sinoussi think this is?
“We should not separate cure research from vaccine research because probably we will need a drug to reactivate the virus from the latently infected cells, and then to come up with a vaccine that induces T-cell response that will be able to eliminate the reactivated T cells,” she says.
“I’m not convinced that the antibody will be enough to reduce the size of the reservoir. I think it is interesting, but not alone – it’s clear that it [a cure] is not a single approach; we will have to combine [approaches], and why not? Maybe we will have different combinations.”
Unveiling the virus
Barré-Sinoussi is equally measured about the use of a modified version of the drug Ciclosporin, traditionally deployed to suppress the immune system of organ transplant patients to prevent rejection. After biologist Professor Greg Towers and his team at University College London unmasked the two molecules that help HIV hide from the immune system – a potentially seismic breakthrough – they then used this drug to block the ‘cloaking’ mechanism in the virus, a development that has caused immense excitement.
“The potential for this approach is huge – as a possible treatment in itself, but also as a complement to existing therapies,” said Towers in 2013.
For Barré-Sinoussi, “it’s too early to say. The approach should be continued to give more convincing data.” But she certainly thinks this particular area is a potentially fruitful avenue. “We understand better the mechanism of persistence of HIV infection and several approaches are based on that. [The use of] anti-inflammatory drugs like Ciclosporin is based on our knowledge that in HIV infection one critical component is inflammation and we know inflammation may play a role in maintaining the reservoir, so this has to be considered.”
Another area to cause frenzied interest in recent months has been a new technique called CRISPR, in which human genomes can be engineered with unprecedented precision: the new wave of gene therapy. Its use has been hailed as a possible breakthrough not only for HIV research but also for genetic conditions such as Down’s syndrome and sickle-cell anaemia. Barré-Sinoussi’s concerns, however, relate to its scalability.
“I cannot see how this kind of approach could be translated and used in a resource-limited setting,” she says, conceding that all these areas of research help build our understanding of the virus like a “puzzle”. However, they cannot, she argues, form the full picture without understanding the profile of a patient: the patient’s genetic background, the quality of the patient’s response to interventions according to his or her inflammatory response, and the patient’s number of latently infected cells, as well as “other markers we still don’t know about”. In a career awash with breakthroughs and disappointment, Barré-Sinoussi knows more than most about the folly of premature hope.