Nevirapine: a review of its use in the prevention and treatment of paediatric HIV infection.

UNLABELLED: Nevirapine is a highly specific inhibitor of HIV-1 reverse transcriptase (RT), an important therapeutic target for the treatment of HIV infection. It was the first non-nucleoside RT inhibitor (NNRTI) to be approved for use in HIV-infected individuals, including children. Nevirapine inhibits replication of multiple HIV-1 strains and clinical isolates in cultured human T cells, but has no activity against other retroviral RTs (including HIV-2 RT) or endogenous human DNA polymerases. Monotherapy with nevirapine rapidly selects for high level drug resistance conferred by a single amino acid substitution in the HIV RT gene. The pattern of resistance mutations selected by nevirapine overlaps with those of other NNRTIs, but is distinct from those of nucleoside analogue RT inhibitors and protease inhibitors. The pharmacokinetics of nevirapine are characterised by rapid and nearly complete oral absorption, an apparently even distribution throughout all organs and tissues in the body, and a long elimination half-life. Nevirapine is both metabolised by and induces the activity of cytochrome P450 isoenzymes. Caution is required when coadministering nevirapine with other drugs metabolised by this system, including HIV protease inhibitors. As a single dose therapy given to pregnant women in labour and to neonates shortly after birth, nevirapine reduced the rate of perinatal HIV transmission by 47% compared with a short course of intrapartum and neonatal zidovudine in a randomised trial in breastfeeding women in Uganda. Nevirapine was more cost effective than zidovudine-based regimens for the prevention of perinatal HIV transmission in a cost-effectiveness model in sub-Saharan Africa. Nevirapine has shown antiretroviral efficacy as part of combination therapy with zidovudine and either didanosine or lamivudine in small numbers of paediatric patients in phase I/II trials. Triple therapy of nevirapine, zidovudine and didanosine was moderately effective in a randomised, nonblind trial in patients with advanced disease. The most frequent adverse event associated with nevirapine is rash, which occasionally develops into severe rash or Stevens-Johnson syndrome. Elevations in liver enzyme levels can occasionally lead to severe complications in patients receiving multiple dose nevirapine.
CONCLUSION: Single dose nevirapine appears to be the most cost-effective of available options for the prevention of perinatal HIV transmission suitable for use in developing countries. In addition, preliminary clinical trial data suggest that nevirapine adds to the efficacy of combination therapy for the treatment of HIV infection in infants and children, and is reasonably well tolerated.