SciDev.Net

A new, more accurate 'real-life' model for trials of HIV vaccines and microbicides in animals is at hand, say the team of researchers who designed it.

Their model proposes giving test animals several low doses of HIV to test a vaccine or microbicide, rather than the more conventional single large dose.

This, the team says, will more closely mimic the way people become infected with the virus.

The researchers, led by Roland Regoes at Emory University in Atlanta, Georgia, United States, published their results online this week (20 July) in PLoS Medicine.

Until now, scientists believed that trials in which animals were given low, repeated doses of HIV – which is the usual pattern of human exposure to the virus — would require unfeasibly large numbers of animals. 

As a result, animals in HIV trials — macaque monkeys, for instance — are given a single high dose of the virus.

Using a computer model, Regoes's team simulated different trials in which monkeys were given different doses of HIV. They found that trials using low doses would require far fewer animals than previously thought.

After running the computer model more than 100,000 times, the team concluded that the ideal dose of the virus is one that infects half the subjects.

But they say that trials in which animals are given just one low dose of HIV would still be too large.

Instead, they say, subjects should be given repeated low doses. This design would work  because it requires fewer animals (the researchers say this could be as few as five per trial group), and mimics real life.

The scientists also suggest how other aspects of HIV trials could be made more realistic. For example, animals in trials should be infected via the vagina or rectum, rather than by injection, to better imitate sexual transmission of HIV in people.

Trials, in which not all animals become infected, can also help answer questions that trials using high doses cannot, say the scientists.

For example, researchers might be able to investigate where the virus gets blocked in animals that do not become infected with HIV. Another question that could be answered, say the scientists, is whether animals that do not become infected gain immunity or whether they are more susceptible.

José Esparza, HIV vaccines advisor to the Bill and Melinda Gates Foundation, told SciDev.Net, "This is the first time I have seen a rationale to seriously consider repeated low-dose virus challenges in future animal [HIV] experiments."

Link to paper in PLoS Medicine

Reference:
PLoS Medicine doi: 10.1371/journal.pmed.0020249.sd001