HPTN Bibliographic Record

Stringer JS, Sinkala M, Chapman V, Acosta EP, Aldrovandi GM, Mudenda V, Stout JP, Goldenberg RL, Kumwenda R, Vermund SH. Timing of the maternal drug dose and risk of perinatal HIV transmission in the setting of intrapartum and neonatal single-dose nevirapine. AIDS. 2003, 17: 1659-65.
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 > or = 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.