In recent years, the use of nevirapine has attracted considerable attention because of its demonstrated efficacy in clinical trials in reducing MTCT, low cost and ease of use in MTCT-prevention programmes. Further information about its use for this purpose is provided below.
Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) that binds directly to HIV-1 reverse transcriptase, slowing the rate of viral DNA synthesis and thereby inhibiting viral replication. Nevirapine is rapidly absorbed when given orally to adults, and has a long elimination half-life t1/2 of approximately 40 hours. Nevirapine crosses the placenta efficiently after a single oral 200 mg dose to the mother at the onset of labour. In infants, median t1/2 ranges from 45 to 72 hours for elimination of the maternal nevirapine, and from 37 to 46 hours for the elimination of a single 2mg/kg neonatal dose.19
Short-term safety and tolerance of single dose nevirapine has been demonstrated in clinical trials. Data from 38 women and infant pairs enrolled in the initial phase I trials, PACTG 250 and HIVNET 006, showed no rash or serious adverse events detected either through laboratory tests of through observation of clinical symptoms in women or infants, attributable to nevirapine. In the HIVNET 01214 and SAINT studies,18 960 women and infant pairs were exposed to the intrapartum/newborn nevirapine regimen; there were no significant differences in serious toxicity, occurrence of rash, anaemia, liver abnormalities or death between nevirapine and short course regimens of zidovudine or zidovudine/lamivudine in women or infants. In the PACTG 316 study, 1506 women receiving antiretroviral treatment (usually combination therapy) were randomized to receive an extra dose of nevirapine or placebo at the time of delivery. There was no difference in maternal or infant toxicity between the two study arms.20 Collection of long-term safety data following administration of single dose nevirapine is ongoing.
Selection of resistant virus has been observed among some women and infants who received single dose nevirapine21,22 or lamivudine.22,23 for preventing MTCT. The resistant virus will revert to wild type susceptible strains within 12 to 24 months after stopping the treatment with nevirapine. The clinical significance of the emergence of resistance in the context of MTCT prevention programmes is as yet unknown, particularly with regard to future treatment options for the mother or the child, or to the outcome of prophylaxis during a subsequent pregnancy if the same drug is used. The WHO Technical Consultation in October 2000 carefully reviewed the available information and concluded that the benefit of decreasing mother-to-child HIV transmission with these antiretroviral drug prophylaxis regimens greatly outweighed concerns related to development of drug resistance.1
Nevirapine and zidovudine were included in the WHO Model List of Essential Drugs in 1999, solely for the indication of MTCT prevention of HIV.24 The HIVNET 012 regimen of nevirapine used for MTCT-prevention is a single 200 mg oral tablet to be taken by the mother at the onset of labour and a single oral dose of nevirapine in suspension (2mg/kg) to be given to the newborn within 72 hours of birth.
Experience in the field suggests that the oral tablet for the mother can be taken at home at onset of labour. However, it is essential that the child should be brought to a health facility within 72 hours of birth for the oral dose of nevirapine in suspension.