AEGiS-DMG: It's the trials, not the drugs: The deaths of five women in HIV/Aids drug trials have been blamed on the handling of the trials rather than the drugs themselves.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

It's the trials, not the drugs: The deaths of five women in HIV/Aids drug trials have been blamed on the handling of the trials rather than the drugs themselves.

Daily Mail & Guardian - Johannesburg, South Africa. April 10 2000
David Le Page

THE deaths of five women in HIV/Aids drug trials were more likely the result of flaws in the handling of the trials than problems with the drugs themselves, researchers working on related trials said last week. The researchers were responding to the controversial decision by the government last week to suspend recruitment of new subjects for anti-retroviral drug trials after it emerged that five patients had died in trials testing a new drug, STC, and involving the widely effective Nevaripine.

Scientists are concerned the decision could stop the use of Nevaripine in preventing mother-to-child transmission of HIV -- a use for which the drug increasingly appears to be effective.

It is arguable whether the problem highlighted by the five STC deaths justifies the sweeping measures that have been taken -- measures which follow the controversy over President Thabo Mbeki's doubts about anti-retroviral drugs.

The five women who died were part of trials being run testing a triple therapy, including Nevaripine and a new drug called STC, related to the better-known 3TC. The trials have been commissioned by the United States drug company Triangle Pharmaceuticals, and are being run at sites across the country.

The mother-to-child trials, also called the Saint trials, have involved extremely low doses of Nevaripine, two to the mother before giving birth, and one to the newborn infant. The Saint trials, run by Jerry Coovadia at the University of Natal, involved more than 1 000 patients, and while the results have yet to be fully analysed, have demonstrated few immediate side effects other than dermatological problems.

According to Coovadia, three women involved in these latter trials have since died, one under anaesthetic, one of chronic Aids-related infections, and one of unknown causes two months after receiving Nevaripine. These are not the women to whom Minister of Health Manto Tshabalala-Msimang referred when announcing in Parliament the decision to halt trial subject recruitment. Coovadia regards it as impossible, though, to reasonably link these deaths with Nevaripine. However, he fully supports an investigation into the STC deaths.

The STC trial deaths, however, highlight not problems with the drug Nevaripine itself, but with the way drug trials are run in South Africa, according to researchers involved in the STC trials themselves.

The researchers said this week that the STC trials are being conducted at several different sites across the country, and that it is far from certain that the same standards are being applied across all the trials. In other words, while proper infrastructure for monitoring the health of trial subjects exists at Chris Hani Baragwanath and other leading research centres, it may not have existed at those sites where the five women died.

One researcher called the anti-retroviral drugs extremely "potent", saying it takes considerable experience to properly administer them. If tests reveal problems, drivers need to be despatched immediately to collect patients so that they can be stabilised. Investigators need to be on hand 24 hours a day to deal with such problems.

Tshabalala-Msimang spoke in Parliament last week of a "problem with the proliferation of clinical trials in South Africa". Her speech suggested that South Africa has proved to be a fertile source of trial subjects for international drug companies, but that South Africans are unlikely to benefit in the long run from being guinea pigs for the rest of the world.

The Ministry of Health has established a new clinical trials committee within the Medicines Control Council for the review of proposals of clinical trials, and this is certainly a positive step.

But it is questionable whether the problems with the STC trial justifies freezing all testing of anti-retrovirals.

"There is no doubt that [anti-retrovirals] work," said Coovadia this week.

Meanwhile, the World Health Organisation and the United Nations Aids programme have formally recommended the use of an antibiotic called Bactrim to counteract secondary infections in African Aids patients. Bactrim is cheap, and while further studies are recommended, one conducted in the C|te d' Ivoire cut morbidity by 50% over a year.

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