Articles criticising nevirapine trial may endanger babies' lives

Three articles published by the Associated Press in mid-December criticising the conduct of a trial of the antiretroviral drug nevirapine in Uganda are threatening to undermine its use in newborn babies in developing countries, according to South African experts. A single dose of the drug given to mothers while in labour and to their babies at the time of birth is known to greatly reduce transmission of HIV from mother to child.

The articles, which appeared in newspapers and were broadcast on radio stations in the United States, Britain, South Africa, and many other countries, made allegations about a trial that was conducted from 1997 to 1999 in Uganda by researchers from Johns Hopkins University and Makerere University in Kampala, Uganda, and subsequently published.

The writer of the articles alleged that leaked documents showed that record keeping in the trial was shoddy, that single use of the drug led to resistance to it in patients in the long term, and that the National Institutes of Health, under whose auspices the trial was conducted, knew of the drug's drawbacks but hid them from the White House until after President Bush announced an initiative on AIDS in Africa in the summer of 2002.

In fact, many experts on HIV and AIDS claim that the articles said little that was not already known about risks associated with the drug and that some of the facts were distorted or wrong. The articles said, for example, that the trial itself showed that single use of nevirapine led to long term resistance, a fact that did not emerge until some time after the trial was ended.

The articles, however, provided ammunition to groups of campaigners who have long been opposed to expanding the provision of HIV treatment in some developing nations.

The source of the leaked documents was Dr Jonathan Fishbein, hired in July 2003 by the Division of AIDS at the US National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), to strengthen the conduct of clinical trials run in collaboration with local researchers in developing countries.

Proceedings are under way to terminate Dr Fishbein's employment, and Dr Fishbein is now claiming that he is being punished for being a “whistleblower.” His allegations can be found at his website at www.honestdoctor.org.

The key findings of the 1997-9 study are not challenged in the articles. A single dose of nevirapine given to mothers while in labour and to their newborn babies was found to be safe and was associated with a transmission rate of HIV of 8.2% at birth. Patients in the control arm of the study received the longer and more expensive regimen of zidovudine, which resulted in a transmission rate of 10.4%. Natural history studies indicate that a quarter to a half of all infants born to HIV infected mothers will, if left untreated, acquire the virus at birth.

The NIH asked the Institute of Medicine of the National Academies, in July 2004, to conduct a full review of the trial. Its report is due in March.

The African National Congress, the governing party of South Africa, which has long been opposed to greater availability of antitretrovirals, seized on the press accounts to charge, in the 17 December issue of ANC Today, that with single dose nevirapine Africans are being “used as guinea pigs.”

It said the NIH had joined “a conspiracy with a pharmaceutical company to tell lies to promote the sales of nevirapine in Africa, with absolutely no consideration of the health impact of those lies on the lives of millions of Africans.”

The grassroots Treatment Action Campaign in South Africa rejected that assessment, however. “There is not a single reported life threatening adverse event associated with this regimen, which is widely used in the developing world.”

UNAIDS, the joint United Nations programme on HIV and AIDS, estimates that 1900 infants become infected with HIV every day throughout the world and that most of those infections could be prevented.

Concerns about resistance resulting from monotherapy led South Africa's Medicines Control Council, in July, to recommend switching to combination antiretroviral treatment for mothers and babies, consisting of nevirapine at the time of birth, followed by several days days of Combivir (a combination of zidovudine and lamivudine). But cost remains a prohibitive factor.

“You can't apply a standard here in Africa that says until we can get the Rolls-Royce of treatment, let's not do anything,” Dr Ashraf Coovadia, the head of the paediatric HIV clinic at Johannesburg's Coronation Mother and Child Hospital, told the Associated Press. He added: “If we pull the plug on nevirapine, many, many more babies will die.”