John S. James Comments On the Future of HIV/AIDS Research

John S. James: Editor and publisher of

AIDS Treatment News

Could a seeming glitch in HIV vaccine progress also be key to getting vaccines to Africa and elsewhere much faster than expected?

Some of the new experimental vaccines do not prevent infection, but may instead greatly lower viral load, preventing or much reducing both illness and transmission. It appears that such "non-sterilizing" vaccines could be tested much faster than those which prevent infection -- by comparing viral loads of persons infected after receiving the vaccine, vs. those infected after receiving the placebo. Probably the first few dozen infections (in both groups combined) would be more than enough for statistical proof -- regardless of the total N (number of people) in the trial (which probably would still be large, but only to show the needed infections sooner). The difference is that with a non-sterilizing vaccine, you can see how well it works in particular individuals. And the inevitable random fluctuation and resulting unbalance in the size of the infected/vaccine vs. infected/placebo groups does not bias the result of the trial -- while this fluctuation does bias the result in a conventional vaccine trial, requiring a larger and longer trial to compensate.

Such a phase III trial might prove a vaccine works within a year or two. Yes, the proven efficacy would then be short term. But even short-term efficacy alone might justify use of the vaccine in epidemic areas, because it would at least reduce transmission (especially during the very infectious primary illness). And later failure of the vaccine would show up quickly in viral load comparisons -- and in case it did, boosters could be tested in the same trial, and proven rapidly in the same way, probably ahead of need in the field (where people would have been vaccinated later). If it's true that non-sterilizing vaccines can be tested much faster than vaccines which prevent infection, the public-health opportunities need immediate attention.

In another area, most but not all researchers have given up on antibodies for helping to control HIV. Clearly, most antibodies produced in response to HIV are not effective. But immunologists are now finding some antibodies that do work -- which may provide a way to rationally design an antibody component of a vaccine (or possibly a treatment). Researchers could quickly screen these vaccines in small trials, to make sure they do indeed produce the antibodies which had been shown effective in laboratory, animal, or human tests.

In other immune-based research, a big problem is standardization of laboratory tests. Immunologists have shown interesting results for many years, but often their work is not followed up because it's hard to compare data from different laboratories. There isn't much commercial incentive as long as the only market is research projects, which often want to develop their own tests anyway. And individual researchers are seldom interested in standardizing tests. NIAID has experience in this area, and we should make sure there are no funding or other avoidable obstacles preventing it from doing this work.

In other areas, pathogenesis research may be able to identify new targets in the development of infection, or of disease -- possibly resulting in new classes of drugs.

As for existing antiretrovirals, we need more research and medical attention to the possibility that safe nutritional or other treatments could help prevent or relieve some of the side effects. Unfortunately this hasn't been a glamorous area. And while pharmaceutical companies have done some research on the causes of drug toxicities, the bottom line is that they make their big money on spin, so they have incentive to avoid raising the public profile of the problems with their drugs. Perhaps the community will have to take the lead in this area -- organizing and applying what's already known, pointing out key strategic research projects, and making sure they get done.