South Africa’s handling of the HIV crisis took a further surreal turn this week with the announcement that the country’s Medicines Control Council could withdraw approval for nevirapine to be used in MTCT prevention within 90 days. The MCC says that irregularities in data collection during the HIVNET 012 study in Uganda cast doubts on the efficacy of nevirapine in the prevention of mother to child HIV transmission.
The doubts arise from a review by the US National Institute for Allergy and Infectious Diseases (NIAID) carried out last year.
During a review of the study, NIAID found that some of the study's data collection did not conform to Food and Drug Administration reporting requirements. However, the data collection irregularities were not considered to affect the reliability of the study’s finding by NIAID.
The MCC has asked nevirapine’s manufacturer Boehringer-Ingelheim to provide data within 90 days proving that nevirapine reduces the risk of mother to child HIV transmission.
In a report commissioned by Boehringer-Ingelheim and submitted to the MCC, South Africa’s leading experts on the prevention of mother to child transmission say: "In our opinion … these [data collection] lapses do not compromise the efficacy and safety data from the trial." Dr James McIntyre and Dr Glenda Gray wrote.
The Treatment Action Campaign in South Africa has condemned the decision, highlighting the studies which support the use of nevirapine.
These include:
- the SAINT study, a comparison of nevirapine and AZT/3TC short course treatment;
- the PEP study, a comparison of a single nevirapine dose versus six weeks of AZT before birth
- the Blantyre study still ongoing in Malawi, which is comparing post-partum treatment for the infant with nevirapine alone or nevirapine plus AZT (preliminary results suggest two drugs are better than one)
No randomised study has found that nevirapine treatment results in significantly greater toxicity, and all studies indicate that nevirapine is either comparable to, or not inferior to, other drugs or combinations of drugs.
From a programmatic point of view, nevirapine retains significant advantages compared to other treatments. It requires very limited dosing and it is supplied free by the manufacturer.
Its only disadvantage is the risk of resistance, which may compromise future treatment options. A large study being conducted at Chris Hani Baragwanath Hospital in Soweto is likely to report on the incidence and durability of resistance acquired during perinatal treatment by the end of 2003.
The MCC’s focus on the HIVNET 012 study is peculiar, given that it has also been in possession of detailed data from the SAINT study since November 2001. The SAINT study compared the efficacy of two doses of nevirapine around the time of labour or AZT/3TC at the onset of labour and for seven days thereafter, and found no difference in the rate of transmission between the two groups. The study also showed no significant differences in tolerability between the arms, and in particular, no unusual incidence of hepatotoxicity in the nevirapine arm.
The MCC has argued that the SAINT trial was designed to demonstrate the superiority of short-course nevirapine over AZT/3TC, and that since it was not set up as an equivalence trial, its findings on the efficacy of short-course nevirapine cannot be inferred.
The South African National AIDS Conference, which starts on Sunday in Durban, is likely to hear more criticisms of the MCC’s decision. Detailed reporting from that meeting will appear on aidsmap next week.
The MCC’s statement
Click here for a pdf version of the MCC statement
Further information on this website
Key studies highlighting efficacy of nevirapine in preventing mother to child transmission