Phase II Study of the Pharmacokinetics of Nevirapine and the Incidence of Nevirapine Resistance Mutations in HIV-Infected Women Receiving a Single Intrapartum Dose of Nevirapine With the Concomitant Administration of Zidovudine/Didanosine or Zidovudine/Didanosine/Lopinavir/Ritonavir

NCT00109590 Phase 2 COMPLETED Results posted

The purpose of this study is to determine which of 3 different anti-HIV drug regimens given to HIV infected pregnant women during and after their pregnancies is most effective in reducing the incidence of nevirapine (NVP) resistance mutations. Blood levels of NVP and lopinavir/ritonavir (LPV/r) will also be studied. Study hypothesis: NVP resistance following single-dose NVP can be prevented with the concomitant administration of additional antiretroviral therapy (ART).

Details

Lead sponsor	National Institute of Allergy and Infectious Diseases (NIAID)
Phase	Phase 2
Status	COMPLETED
Enrolment	175
Start date	2006-06
Completion	2009-11

Conditions

• HIV Infections

Interventions

• Didanosine, enteric-coated
• Lopinavir/ritonavir
• Nevirapine
• Zidovudine

Primary outcomes

• The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum). — within 8 weeks postpartum.
  The incidence of new NVP resistance mutation in plasma HIV within 8 weeks postpartum in each randomized arm was estimated using an exact binomial confidence interval. If a resistance mutation was detected at any of the timepoints then an endpoint was met. Samples with VL \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml (e.g.missed visit), it was conservatively imputed as resistant in the primary analysis.
• The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma — at Day 10 or Week 6 postpartum.
  The incidence of new NVP resistance mutations at day 10 or week 6 postpartum in each randomized arm. Samples with viral load \<500 copies/mL were considered free of mutations. If a resistance result was missing for reasons other than VL \<500 copies/ml it was conservatively imputed as resistant in the primary analysis.
• Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL) — Within 72 hours postpartum and during the first 30 days postpartum
  Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
• Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) . — Within 72 hours postpartum and during the first 30 days postpartum
  Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
• Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL). — Within 72 hours postpartum and during the first 30 days postpartum
  Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.
• Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL). — Within 72 hours postpartum and during the first 30 days postpartum
  Data was analyzed with WinNonLin (Version 5.2, Pharsight, USA) using non-compartmental methods. The pharmacokinetic parameters were calculated using the linear-trapezoidal rule. Cpredose and C4hour at the two measurement times were compared within-subject using the Wilcoxon signed-rank test.

Countries

Thailand