Trial suggests vaccines could aid HIV therapy

from Nature

Erika Check

Brigitte Autran thinks the vaccines can augment drug therapies for managing HIV.

A therapeutic vaccine could help patients with HIV to take a break from their exacting drug treatments, according to a prominent immunologist.

Brigitte Autran, a physician at the Pitié-Salpêtrière Hospital in Paris, revealed the results of her recent study on 3 April at a Keystone symposium on HIV vaccines in Banff, Canada.

At the very least, Autran claims, the study offers the best evidence yet for the promise of a therapeutic vaccine in managing HIV. But the small size of the clinical trial has led some researchers to question the findings.

"Our results suggest that a vaccine that does not provide sterilizing immunity could still have an impact on the clinical management of the disease," Autran told the meeting. "This is one of the first proofs of principle supporting the concept of therapeutic immunization."

A therapeutic vaccine would not stop people from contracting HIV. But, in theory, it could be used to boost the immune systems of individuals with HIV who are undergoing 'highly active anti-retroviral therapy' (HAART).

Many HIV patients in wealthy countries are now being prescribed HAART in an effort to delay the onset of AIDS. It suppresses HIV but also causes harsh side-effects, and patients eventually develop resistance to the treatment. Using a therapeutic vaccine to boost the body's immune system in the fight against the virus might allow patients to take a break from HAART. This would provide both a respite from the side-effects and an extension to the useful lifetime of the therapy.

Autran says that her trial is the first to show that a vaccine can do just that. She and her colleagues injected 48 HIV-infected people on HAART with a therapeutic vaccine, which contained HIV genes stitched into a harmless bird virus.

Autran says that more than half of the patients developed immune responses to the vaccine. All of the patients then went off HAART, and doctors measured how long their immune systems could control HIV. Those who developed immune responses to the vaccine managed to stay off HAART for a median of 10 weeks, around 18 days longer than those who did not respond, Autran says. Although she admits that the effect was relatively small, Autran says that it could be amplified with better vaccines.

Other scientists point out that Autran's trial did not include a control group of patients on HAART who did not receive the vaccine, so it is hard to know whether the vaccine actually benefited the patients. Researchers such as Martin Markowitz and his colleagues at the Aaron Diamond AIDS Research Center in New York have also found that patients on HAART can develop strong immune responses to vaccines. But in the long term, this did not allow the patients to stay off HAART any longer than patients who were not vaccinated (M. Markowitz et al. J. Infect. Dis. 186, 634–643; 2002).

"Autran's data confirm the fact that the immune system can control the virus to some degree," Markowitz says, "but the challenge is whether we can harness the immune system to control the virus over the long term."

This does not invalidate the therapeutic-vaccine approach, Markowitz adds. Like Autran, he believes that better vaccine candidates could translate into stronger results. Both he and Autran used the best vaccines available for their trials, but newer vaccine candidates might prove to be more effective.

Convincing regulators to approve a therapeutic HIV vaccine may be a challenge in itself, however, as it is unclear what data would be needed to indicate efficacy. Most vaccines work by blocking infection entirely, says Alan Landay, an immunologist at Rush Medical College in Chicago. Landay is organizing a meeting in Washington later this month to bring government officials, industry representatives and scientists together to talk about how best to proceed with therapeutic vaccines.