Timing of the maternal drug dose and risk of perinatal HIV transmission in the setting of intrapartum and neonatal single-dose nevirapine
Stringer, J.S.A.; Sinkala, M.; Chapman, V.; Acosta, E.P.; Aldrovandi, G.M.; Mudenda, V.; Stout, J.P.; Goldenberg, R.L.; Kumwenda, R.; Vermund, S.H.
Aids 17(11): 1659-1665
2003
ISSN/ISBN: 0269-9370 PMID: 12853748 Document Number: 249653
Context: Single-dose intrapartum and neonatal nevirapine (NVP) reduces perinatal HIV transmission and is in increasingly common use throughout the developing world. Objective: We studied risk factors for perinatal transmission in the setting of NVP. Design and setting: A prospective cohort study at two public obstetrical clinics in Lusaka, Zambia. Patients and methods: In a volunteer sample of HIV-infected pregnant women and their newborns, the women received a 200 mg oral dose of NVP at the onset of labor; their infants received 2 mg/kg of NVP syrup within 24 h of birth. The main outcome measure was the infant HIV infection status at 6 weeks of life, determined by DNA polymerase chain reaction. Results: Only 31 of 278 (11.2%) infants were infected at 6 weeks. In logistic regression, viral load exceeding the median (adjusted odds ratio (AOR), 3.1; 95% confidence interval (CI), 1.1-8.7) and 1 h or less elapsing between NVP ingestion and delivery (AOR, 5.0; 95% CI, 1.8-14) were associated with transmission. Women delivering within 1 h of NVP ingestion had a lower mean drug concentration (351 versus 942 ng/ml; P < 0.001) and were more likely to have a 'sub-therapeutic' NVP level of less than 100 ng/ml (56 versus 20%; P < 0.001) than those who delivered more than 1 h post-ingestion. However, concentrations < 100 ng/ml were not more likely to be associated with transmission than concentrations gtoreq 100 ng/ml (12.9 versus 11.7%; P = 0.8). We did not identify a threshold concentration below which risk of transmission increased. Conclusions: We confirmed low perinatal transmission rates with single-dose NVP. At least 1 h of pre-delivery NVP prophylaxis was a critical threshold for efficacy.