With additional reporting from PLUS NEWS
The South African government is looking to terminate its pilot trial into the safety and effectiveness of nevirapine in preventing mother-to baby transmission of HIV after the Food and Drug Adminstration (FDA) in the USA effectively refused to license the drug for this purpose.
Nevirapine manufacturer Boehringer-Ingelheim withdrew its application after the the National Institute of Allergy and Infectious Diseases (NIAID) in the US raised questions about data collection in the key 1999 clinical trial in Uganda which showed that the drug was safe and effective in preventing mother to baby transmission of HIV.
Boehringer Ingelheim had applied to the US Food and Drug Administration for a US licence to allow the use of nevirapine for the prevention of mother-to-baby transmission.
Although a spokesperson for the FDA described the problems with the study as "potentially quite serious", Dr. John R. LaMontagne of the NIAID, which paid for the 1999 study, said that there was no question about the validity of the study's conclusions, rather the problem was with "rather arcane requirements in record keeping." These are focused on the description and recording of "serious adverse events."
The 1999 Uganda trial, which as conducted by researchers from John Hopkins University in the US, was not sponsored by Boehringer Ingleheim and nor was it designed for product registration purposes. The finding were put before the peer review panel of the prestigious UK medical journal The Lancet which subsequently published an article on the study.
A new application for a US licence for nevirapine for the prevention of mother-to-baby transmission will be made by Boehringer Ingleheim once the issues had been resolved pointing out that there was no reason to suspect the validity of the trial's fundamental conclusions.
The World Health Organisation has issued a statement saying that the apparent reporting irregularities in the 1999 trial did "not warrant any change in the recommendations issued following a WHO technical consultation on mother-to-child HIV transmission in October 2000" on the safety and effectiveness of nevirapine.
Alarmingly, the problems raised by the FDA are being used by the South African government to call into question to the continuation of its pilot trial at 18 state run hospitals into nevirapine and the prevention of mother-to-baby transmission of HIV. South African high court judge Chris Botha recently ordered the South African authorities to make the drug available to HIV-positive pregnant women immediately, and several provincial governments in South Africa have recently initiated their own nevirapine programmes. However, South Africa's regulatory body, the Medicines Control Council (MCC), has announced that it will review the use of nevirapine for prevention of mother to cchild transmission, a move that could lead to the de-registering of the drug if the Commmission is unhappy with the doumentation of adverse events in the HIVNET 012 study.
"There is no reason why they [the MCC] should [withdraw registration for nevirapine] as one would think that their independence would be compromised," Treatment Action Campaign (TAC) spokesman Nathan Geffen told Plus News on Monday.
The implications for the government's MTCT pilot projects were raised on Friday in the Pretoria High Court, where the state was seeking to overturn a court order which required them to make nevirapine available to all HIV-positive pregnant women.
The government's advocate, Marumo Moerane, told the court the state would shut down its pilot sites if nevirapine's registration was withdrawn or if new investigations revealed fraudulent reporting and documentation in the Ugandan study.
However, the court ruled that although a Constitutional Court appeal is pending, the government must obey the order to supply the drug.
Meanwhile, the African National Congress, the ruling party in South Africa has just published a report circulated to all regional offices highlighting the toxicity of anti-HIV drugs, questioning the link between HIV and AIDS and attacking drug company profiteering. Boehringer Ingelheim makes nevirapine available free of charge to developing countries with a serious HIV problem for the prevention of mother-to-baby transmission.