The Medicines Control Council (MCC) played with semantics at the South African Aids conference on Wednesday when it said it would not ban nevirapine — except, perhaps, for use in preventing mother-to-child transmission of HIV.
Speaking before a packed plenary at lunchtime on Wednesday, MCC registrar Precious Matsoso’s play on words was heckled by delegates.
Sketching how the MCC had arrived at its decision to withdraw nevirapine for use in preventing mother-to-child transmission of HIV (PTMCT), she talked of problems with a Ugandan study on nevirapine, HIVNET012.
This is despite the fact that the US National Institutes of Health and the World Health Organisation made submissions to the MCC saying that the queries on the study were bureaucratic and not safety — or efficacy-related.
Nevirapine is one of the drugs, along with AZT and Combovir (AZT and 3TC) recommended by the US health authorities for PTMCT.
The MCC last week said that unless manufacturers, Boehringer Ingelheim could produce more efficacy data in 90 days the drug would be deregistered for use in PTMCT — but would remain accessible to long-term Aids patients.
Matsoso was critical of the fact that there were ”glaring differences between the designs” of a major South African based study into nevirapine, the SA Intrapartum Nevirapine Trial (Saint) and the Ugandan trial.
Professor James McIntyre, head of the Perinatal HIV Unit at Soweto’s Chris Hani Baragwanath hospital, who participated in and helped design Saint, said such differences were part of scientific research and did not negate the findings of either trial, namely that nevirapine was safe and efficient in PTMCT.
He warned that the lives of 2 200 babies born each day to HIV-positive mothers would be at risk if they did not receive nevirapine.
He said that between 80 000 to 100 000 mothers and babies had already received the drug in South Africa over the last two years, with, on average, less than 10% of the babies becoming HIV-positive.
Before widespread use of nevirapine the SA Paediatric Association reported in 2000 that at that stage 7 000 babies were dying of Aids each month.
Matsoso said the MCC provisionally approved nevirapine for use in PMTCT and in government pilot sites in March 2001. This conditional approval was based on the Ugandan trial results and followed ”no real safety concerns reported in 2000 with the Saint study”.
She said the MCC did not accept the Ugandan trial as a ”pivotal study” — although McIntyre pointed out that 71 other countries in the world using nevirapine for PTMTCT had, with South Africa now the only exception.
Matsoso said too, that the Saint report could not be accepted as pivotal because there were ”problems with its design. Expert reports cannot substitute for clinical data and therefore nevirapine does not meet regulatory requirements for use in PTMCT”.
Nonetheless, Matsoso said nevirapine was ”important in public programmes. A generic nevirapine and other generic anti-retrovirals have been registered to facilitate access to treatment”.
However, she did not point out, although McIntyre did, that only AZT is registered for PMTCT. It is more expensive and needs to be administered to each baby for a week instead of nevirapine’s single dose.
Catherine Wilfert of the Elizabeth Glaser Paediatric Aids Foundation in Washington said the Ugandan trial revealed that single dose nevirapine (a tablet to the mother in labour, and a teaspoon of syrup to baby three days after birth) saw only 15,7% of babies become HIV-positive. In comparison, a single dose of AZT to mother during labour and a week’s treatment to the baby saw 25,8% become HIV-positive.
In the Saint trial, she said, single dose nevirapine saw only 12,3% of babies become HIV-positive. AZT and 3TC used in combination had greater success, with only 9,3% of babies becoming HIV-positive.
Again, it is more expensive. Also it requires mother and baby to receive the drugs for a week, and is two drugs instead of just one.
According to research presented by Wilfert, South Africa had the world’s third-highest rate of HIV-positive pregnant women, at around a quarter of all pregnant women. Zimbabwe has the second-highest rate.
Botswana has the highest incidence of HIV-positive pregnant women at around 48%. Botswana has in the last two years developed extensive PTMTCT sites to combat its high HIV infection figures.
Wilfert presented further research that showed that only Rwanda gives nevirapine to more pregnant women — in percentage terms — than South Africa, close to 80% for Rwanda, with close to 70% for South Africa.
SA is closely followed by Uganda, which although it has significantly less HIV infections, has a wider range of treatment sites. Zambia, the Democratic Republic of Congo and Zambia follow in that order. – Sapa