After the shock of the second failure of an HIV-1 vaccine in Phase III trials recently – detailed to some extent here – we were surely due some relief.
And it is here: William Borkowsky and team have just published in AIDS and Human Retroviruses a paper which describes what amounts to successful “autologous immunisation” of a paediatric HIV-infected cohort by a series of progressively longer treatment interruptions, or drug holidays.
The children, who ranged in age from 4 to 19, were all on HAART or highly active anti-retroviral drug therapy, and all had initially undetectable viral loads. The subjects in the experimental arm of the trial were given a series of drug holidays of progressively increasing length over up to 17 cycles of treatment in some cases. In the words of the authors:
“Increased HIV-specific immune responses and decreased HIV RNA were seen in those children who have had >10 cycles of antiretroviral discontinuations of increasing durations acting as autologous virus vaccinations. Other studies may have failed due to an insufficient number of exposures to HIV; most of the studies had fewer than six drug interruptions.”
This is a quite momentous finding: given that it is known that increased CD8+ T-cell responses to Gag proteins of HIV are correlated with decreased viral load in infected patients, this means that many times-repeated exposures of immunocompetent people to live virus seems to successfully elicit suitable immunity and reduce viral load, just as a vaccine could be wished to do.
But in all the vaccine trials, and in previous treatment interruption trials, no more than 4 vaccinations or 6 drug interruptions were performed – which may mean, given the lack of persistence of T-cell as compared to antibody responses, that simply too few treatments have been given in the past.
So is the solution to dose people considerably more often in prophylactic vaccine trials aimed at protecting against HIV infection?
And possibly with subunit vaccines (such as our recent offering…B-) or killed whole-virus vaccines instead of “genetic vaccines” such as the DNA and virus-vectored HIV gene vaccines which have been so popular up to now?
We need to explore these possibilities – and to explore them soon. There is a lot riding on the outcome….