A funding bonanza that will save lives

Professor Salim Abdool Karim, one of the world's most respected AIDS scientists, is understandably a very happy man. After years of underfunding and a lack of resources, he can now confidently state that scientists in South Africa are now not only willing, but also able, to undertake cutting edge research on HIV/AIDS.

This week, the National Institute of Health (NIH), America's most powerful and influential health body, awarded Professor Karim and the cream of South African scientists a massive R120 million for their research over the next five years.

"We were asked to suggest projects for an AIDS research programme in South Africa," explained Professor Karim. "Two key projects were chosen. I have to say it's almost like a dream come true. With a budget in excess of R25 million in the first year alone, we can now do the science that we have always talked about."

The ethos of the newly formed Centre for the AIDS Programme of Research in South Africa (CAPRISA) is to pursue research suited to the local environment. The projects are ambitious and enormously far-reaching, but as Karim puts it "so feasible" that they are just waiting to be tested.

"Imagine that the day arrives when we are offered free or affordable anti-retroviral drugs for all people who need them," says Karim. "Where would we start? How would we identify en masse those whose viral loads and CD4 cells are at a stage where opportunistic diseases may occur? Those are the people who will need anti-retrovirals."

However, adherence to the drugs, which often have nasty side-effects, is the biggest challenge. Karim and his team believe the answer lies in the links between HIV and tuberculosis. In South Africa, TB is commonly the first opportunistic disease affecting those with HIV, and TB has similar drug adherence problems. Says Karim: "The first onset of TB in AIDS patients commonly indicates that the patient is just below the viral load cut-off level for AIDS therapy - being 200 cells per cubic centimetre of blood. As most TB cases are part of the Directly Observed Treatment Strategy (DOTS), we have an ideal opportunity for administering anti-retrovirals as well."

Using the AIDS-TB link could mean that the anti-retroviral treatment could be developed with TB services, avoiding the kinds of infrastructure problems that have been experienced in the provision of Nevirapine. But now come the difficult research questions:

Would four TB drugs per day, plus three anti-retrovirals be too large a burden for an already weakened immune system? If there were side-effects from the AIDS therapy, would they compromise the TB programme? Would it be better to treat the TB first and then administer anti-retrovirals at a later stage? "Only research will give us those answers," says Karim.

Taking part in the research will be about 500 patients from the Cyril Zulu Communicable Disease Centre in Warwick Avenue, all of whom have both TB and AIDS. It will be a randomised trial, some receiving TB and AIDS therapy together, while others receive the treatments sequentially.

The second research project will ask this question: How, besides through behavioural changes, can we reduce the risk of HIV-infected people spreading HIV/AIDS to others? Explains Karim: "We need to determine exactly why, after initial infection, the viral load drops to different levels. In some people it will go to almost undetectable levels and stay there for several years. In others it will be at a higher level and cause an earlier onset of full-blown AIDS."

"Is it nutrition? Are other diseases present at the time of infection? The exciting thing is that with state-of-the-art equipment, we can now examine these different infected blood levels and hopefully discover the answers. Once we know what keeps viral loads down, we can start to identify ways to contain the spread of the disease."

Commercial sex workers from KwaZulu-Natal will be involved in this research. It is hoped to track them at the earliest onset of infection. Research could also show why many of the sex workers, despite the risky nature of their lives, often have remarkably low viral load levels.

He said that another high priority on the investigative side is to track and understand the extraordinary mutation capabilities of HIV. "We need to better understand the viral escape mode. By the time the immune system and antibodies have recognised the virus, the virus has already changed its appearance. This time-lag and possible ways to speed up the immune system response can now be investigated."

Three core projects are also part of the five-year funding project: new infrastructure (which includes the setting up and standardisation of laboratory assays and a biostatistics facility for collecting data), the administration of a nationwide research programme and the training of a new generation of young researchers, especially those from disadvantaged backgrounds.