Clinical trial NCT00109590
Conditions: HIV Infections
Keywords: HIV Seronegativity Treatment Naive Pregnancy Perinatal Transmission Vertical Transmission Mother-To-Child Transmission MTCT
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2006-06-01; Completion date: 2009-11-01
Enrollment: 175 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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).

Detailed description:
A single dose of nevirapine (SD-NVP) given to an HIV infected pregnant woman in labor followed by a single dose to her infant had been shown to be a simple and effective means of reducing mother-to-child transmission (MTCT) of HIV among women who had not received antiretroviral (ART) during pregnancy. However, development of NVP and other nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant virus was a concern. An optimal ART regimen that can prevent selection of resistant virus while efficiently preventing MTCT was needed. This study evaluated 3 different ART strategies for preventing the development of NVP resistance in HIV infected pregnant women and compared the incidence of NVP resistance mutations postpartum observed with each regimen to the incidence among historical controls. NVP and LPV/r pharmacokinetics (PK) were also evaluated in this study.

Participants were randomly assigned to one of three study arms. All study participants received a single dose of oral NVP at the onset of labor and, oral zidovudine (ZDV) at the onset of labor, and every three hours during labor. Arm A: (LPV/r x 7d) participants received enteric-coated didanosine (ddI) and LPV/r orally twice daily beginning at the onset of labor and continuing through 7 days postpartum; oral ZDV was also taken twice daily for 7 days postpartum. Arm B: (no LPV/r) participants received enteric-coated ddI beginning at the onset of labor and continued through 30 days postpartum; oral ZDV was also taken twice daily for 30 days postpartum. Arm C : (LPV/r x 30d) participants received enteric-coated ddI and LPV/r orally twice daily beginning at the onset of labor and continued through 30 days postpartum; oral ZDV was also taken twice daily for 30 days postpartum.

All women were followed for at least 24 weeks postpartum. Women with resistance mutations identified within 8 weeks postpartum were to be followed until 72 weeks postpartum to evaluate the persistence of the mutations. All infants were followed until at least 12 weeks of age. HIV-infected infants were to be followed until 24 weeks of age. There were 11 study visits for women at day 10, 21, and 30 and week 5, 6, 8, 12, 24, 36, 48, and 72. Medical history assessment, a physical exam, and blood collection occurred at all visits. Blood collection for PK studies occurred at Days 10, 21, and 30. All women were asked to complete an adherence questionnaire at Day 10; women assigned to Arms A : LPV/r x 7d and B: no LPV/r were also asked to complete an adherence questionnaire at Day 30. There were 6 study visits for infants at birth - 48 hours, day 21, week 5, 12, 16 and 24. Medical history assessment and a physical exam occurred at most visits; blood collection occurred at all visits.

Data and specimens for the historical control comparison group were obtained from the PHPT-2 trial\*, in which five of the P1032 study sites had participated between 2001 and 2003. PHPT-2 was a study of the efficacy of SD-NVP to prevent MTCT among women who received ZDV after 27 weeks gestation but no postpartum ART. Criteria for inclusion in the historical comparison group included receipt of SD-NVP, a CD4 count of more than 250 cells per cubic millimeter within 30 days of screening or entry, and the availability of plasma samples at 10 days or 6 weeks post-partum.

\* Lallement M, Jourdain G, Le Coeur S, et al. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med 2004; 351:217-28.

Arms: arm 1: NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and BID for 7 days postpartum, ddI 250 mg orally daily (if body weight \<60 kg) or 400 mg orally twice daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 7 days postpartum, LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 7 days postpartum. arm 2: NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 7 days postpartum , ddI 250 mg orally daily (if body weight \<60 kg) or 400 mg orally daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 30 days postpartum. arm 3: NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 7 days postpartum , ddI 250 mg orally daily (if body weight \<60 kg) or 400 mg orally daily (if body weight \>= 60 kg) at the onset of labor, during labor, and for 30 days postpartum,LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 30 days postpartum.
Interventions: intervention 1: Didanosine, enteric-coated intervention 2: Lopinavir/ritonavir intervention 3: Nevirapine intervention 4: Zidovudine
Intervention descriptions: intervention 1: once daily intervention 2: twice daily intervention 3: single-dose at the onset of labor intervention 4: twice daily

Protocol documents: