Nevirapine can be given safely once a day to breast-feeding infants as a strategy to reduce the risk of mother-to-infant transmission, according to a new study from southern Africa. However, the efficacy of this strategy is yet to be proven.
Breast-feeding is known to double the rate of mother-to-child HIV transmission of HIV, with most cases occurring during the first few months of life.
Dr Avinash Shetty and colleagues conducted the dosing study HIVNET 023 in 75 breast-feeding infants born to HIV-infected mothers in Chitungwiza, Zimbabwe, and Durban, South Africa. The study was designed to investigate the safety and minimum dosing schedule to maintain a nevirapine trough concentration above 100 ng/ml (ten times the 50% inhibitory concentration) among breast-feeding infants for 24 weeks.
Infants received one of three nevirapine doses: once-weekly (4 mg/kg from birth to 14 days, then 8 mg/kg from 15 days to 24 weeks); twice-weekly (4 mg/kg from birth to 14 days, then 8 mg/kg from 15 days to 24 weeks); and once-daily (2 mg/kg from birth to 14 days, then 4 mg/kg from 15 days to 24 weeks).
Drug concentration data clearly favoured the once-daily dose. In the once-weekly group, only 36% of infants had minimum drug concentrations above the therapeutic target of 100 ng/ml. In the twice-daily group, 62 of 65 infants (95.4%) of infants achieved the target trough concentration, and all infants in the once-daily group achieved the target cut-off.
Sixty-three infants completed follow-up to 32 weeks. The drug was well tolerated, with no severe cases of skin rash or liver or kidney toxicity. The three deaths which occurred were unrelated to the study drug: one due to sepsis and two due to HIV-associated pneumonia.
Thirty-six infants were tested for HIV infection at weeks 24 and 36 using the Roche Amplicor assay. Of the four infants found to be infected with HIV, two were deemed to be infected with HIV prior to birth, one between weeks 2 and 8, and the fourth was infected between weeks 24 and 32. Three infections occurred in the once-weekly group and one occurred in the twice-weekly group.
Due to the low number of infants involved, Shetty and colleagues state that no conclusions can be drawn regarding the efficacy of the dosing regimens in the prevention of post-delivery mother-to-child HIV transmission. However, they state that once-daily nevirapine is “an attractive option for a phase 3 study” to evaluate ability of nevirapine to prevent HIV transmission during breast-feeding.
Shetty A.K. et al. Safety and trough concentrations of nevirapine prophylaxis given daily, twice weekly, or weekly in breast-feeding infants from birth to 6 months. Journal of Acquired Immune Deficiency Syndromes 34(5): 482-290, 2003.