Short course of zidovudine cuts transmission of HIV

The rates at which HIV is transmitted from infected mothers to their infants can be halved by a treatment regimen that is shorter and less expensive than the accepted standard of care, the Centers for Disease Control and Prevention in the United States announced last week.

The finding is particularly relevant to developing countries, where 90% of new HIV infections are estimated to occur. The World Health Organisation estimates that over the next five years 5-10 million children will contract HIV perinatally: most of them will be in the developing world.

For four years the antiretroviral drug zidovudine has been known to reduce perinatal transmission of HIV. In 1994 the AIDS Clinical Trials Group 076 showed that a treatment regimen of zidovudine reduced perinatal HIV transmission by up to 70%. Under the 076 regimen, a pregnant woman with HIV infection begins taking zidovudine at 24 weeks of pregnancy and continues to take it throughout the rest of her pregnancy. She receives an intravenous dose of zidovudine during labour, and the newborn baby is also given zidovudine. This has now become standard care in the United States.

Although the 076 regimen is effective, it is expensive—around $800 (£500) per treatment—and impractical in areas where intravenous drugs cannot be delivered in a sterile environment. So the goal has been to find a way of using the same drug with a comparable rate of effectiveness but at less expense.

In April 1996 the Centers for Disease Control and Prevention, in collaboration with the ministry of health in Thailand and the United Nations Programme on HIV/AIDS (UNAIDS), began enrolling women in two placebo controlled trials to determine the effectiveness of a shorter, oral course of zidovudine. One trial took place in Bangkok, Thailand, and the other in Abidjan, Côte d'Ivoire, Africa.

Because transmission is thought to occur towards the end of pregnancy, the short course entails giving pregnant women with HIV infection zidovudine during the last three or four weeks of pregnancy and an oral dose during labour. No dose is given to the newborn infant. Interim data just released from the Thailand study show that mother to infant transmission of HIV is reduced by 50% at a cost of $50 per treatment. The Centers for Disease Control and Prevention said that as the regimen has now been shown to be safe and effective, all the pregnant women in the Abidjan study would receive the short course zidovudine regimen.

“We now have statistical evidence that a short course works,” said Dr Timothy Dondero, from the division of HIV/AIDS prevention at the Centers for Disease Control and Prevention. “Fifty per cent is not high enough to think about not trying to improve but, pragmatically, it's enough to try to start delivery.”

Yet while the study has been hailed as a breakthrough for women in developing countries, it has also been the subject of much controversy within the world of scientific and medical research. The trials were sponsored by the Centers for Disease Control and Prevention and formed part of 15 ongoing placebo controlled clinical trials that were funded by different organisations throughout the developing world—all with the same goal of finding an effective and less expensive means to reduce transmission of HIV from mother to infant.

Controversial study

Critics have attacked the use of placebo rather than the effective 076 regimen, which places infants who could have been saved from contracting HIV at unnecessary risk. The rate of HIV infection from mother to infant, while widely inconsistent from area to area, is between 18% and 24%.

In an editorial on 18 September 1997 Dr Marcia Angell, the executive editor of the New England Journal of Medicine, compared the placebo controlled trials with the Tuskegee study. This study, which lasted from 1932 to 1972, tracked the progression of untreated syphilis in a cohort of black men and continued even after penicillin became available and was known to be effective in treating the disease.

The Centers for Disease Control and Prevention argued, however, that the placebo controlled design allowed new regimens to be compared with the current standard of care in the developing world (which mostly amounts to no intervention) and to identify any potential side effects associated with the new regimens.

Dr Sidney Wolfe, director of Public Citizen, a non-profit agency that monitors medicine and science, in an editorial in the same issue of the journal, says this logic creates a double standard in medical research, “which permits research designs that are unacceptable in the sponsoring country, and creates an incentive to use as research subjects those with the least access to health care.”

Dr Wolfe has uncovered data from the original study of the AIDS Clinical Trial Group 076 which, he says, should have been considered in the design of future trials. The 076 study measured the long course of zidovudine treatment against placebos to show effectiveness, but a subset of women received a course of zidovudine over 17 weeks that was effective. The Centers for Disease Control and Prevention has said this evidence was not strong enough.

Adrienne Germain of the International Women's Health Coalition in New York said that the findings were good news, but more needs to be done. “We don't have out of this research a silver bullet,” she said. “It's useful, but not useful enough.”

UNAIDS will hold an international meeting in March to discuss the implications of the study.

90% of new HIV infections occur in developing countries

BUREAU BANGKOK/IMPACT