title: Timing of the maternal drug dose and risk of perinatal HIV transmission in the setting of intrapartum and neonatal single-dose nevirapine.
abstract: BACKGROUND
  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.
  
  
  METHODS
  A prospective cohort study at two public obstetrical clinics in Lusaka, Zambia.
  
  
  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.
authors.affiliation: Schools of Medicine and Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA. stringer@uab.edu
authors.forename: Jeffrey S A
authors.initials: JS
authors.lastname: Stringer
authors.forename: Moses
authors.initials: M
authors.lastname: Sinkala
authors.forename: Victoria
authors.initials: V
authors.lastname: Chapman
authors.forename: Edward P
authors.initials: EP
authors.lastname: Acosta
authors.forename: Grace M
authors.initials: GM
authors.lastname: Aldrovandi
authors.forename: Victor
authors.initials: V
authors.lastname: Mudenda
authors.forename: Julia P
authors.initials: JP
authors.lastname: Stout
authors.forename: Robert L
authors.initials: RL
authors.lastname: Goldenberg
authors.forename: Rosemary
authors.initials: R
authors.lastname: Kumwenda
authors.forename: Sten H
authors.initials: SH
authors.lastname: Vermund
mesh_terms: D000293:Adolescent; D000328:Adult; D001942:Breast Feeding; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D006679:HIV Seropositivity / Q000175:diagnosis; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007743:Labor, Obstetric; D019829:Nevirapine / Q000008:administration & dosage* / Q000627:therapeutic use; D007744:Obstetric Labor Complications / Q000188:drug therapy*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012307:Risk Factors; D013997:Time Factors
chemical_list: D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine