Clinical trial NCT00099632
Conditions: HIV Infections
Keywords: Treatment Naive
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2006-03-01; Completion date: 2011-11-01
Enrollment: 484 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
HIV infected pregnant women may take single-dose nevirapine (SD NVP) prior to giving birth to prevent mother-to-child transmission (MTCT) of HIV. However, SD NVP may cause NVP resistance in the mother, potentially ruling out some treatment options in the future. The purpose of this study is to determine which of three anti-HIV drug regimens most effectively reduces the development of maternal NVP resistance in HIV infected pregnant women. The effectiveness of short-term (7 day therapy) versus long-term (21-day therapy) regimens will also be compared.

The study hypotheses are: 1) intrapartum SD NVP with a 21-day course of antiretroviral therapy (ART) results in less frequent selection of NVP-resistant HIV-1 variants than intrapartum SD NVP with a 7-day course of ART, and 2) a 7- or 21-day course of lamivudine/zidovudine (3TC/ZDV), emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), or lopinavir/ritonavir (LPV/r) following SD NVP will not select nucleoside reverse transcriptase inhibitor (NRTI)- or protease inhibitor (PI)- resistant HIV-1 variants.

Detailed description:
A major disadvantage of giving SD NVP is the potential for maternal development of NVP resistance and additional resistance to other nonnucleoside reverse transcriptase inhibitors (NNRTI) in the mother; as a result, future treatment options may be limited for these HIV infected women. The purpose of the study is to determine which of three ART regimens most effectively deters the development of maternal NVP resistance in HIV infected pregnant women postpartum. This study also compared the effectiveness of short-term versus long-term ART in discouraging the development of maternal NVP resistance.

Some mothers in this study received ZDV monotherapy prior to SD NVP administration; initiation of ZDV monotherapy was at the discretion of the site investigator and was be provided by this study. Randomization was stratified by receipt of ZDV monotherapy during the pregnancy.

Prior to labor, mothers were randomly assigned to receive SD NVP at the onset of labor and one of three postpartum ART regimens: 3TC/ZDV, FTC/TDF, and LPV/r. In addition, participants were randomly assigned to receive 7 or 21 days of their assigned postpartum treatment.

Mothers were followed for 96 weeks following delivery; there were 11 study visits for mothers during the study. At the onset of labor, medical and medication history, a targeted physical exam, and an obstetrical exam occurred. Additional physical exams occurred on Day 1 and Weeks 1 and 3. Blood collection occurred at 8 study visits between Weeks 3 and 96. Infants were followed for up to 96 weeks after birth; there were 8 study visits for infants during the study. Infants who had ever been breastfed had study visits at Weeks 16, 24, 48, and 96, and at about 1 and 2 years of age. A physical exam, medication history, and blood collection occurred at each infant visit. Mothers and infants could be prescribed continuing ART, but such ART was be provided by this study.

Arms: arm 1: SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV. arm 2: SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV. arm 3: SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF. arm 4: SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF. arm 5: SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r. arm 6: SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Interventions: intervention 1: Emtricitabine/Tenofovir Disoproxil Fumarate intervention 2: Lamivudine/Zidovudine intervention 3: Lopinavir/Ritonavir intervention 4: single dose Nevirapine
Intervention descriptions: intervention 1: 200mg/300mg as one tablet taken orally once daily intervention 2: 150mg/300mg as one tablet taken orally twice daily intervention 3: 133.3mg/33.3mg as three capsules taken orally twice daily intervention 4: one 200 mg tablet taken orally

Protocol documents: