Maintaining Options for Mothers Study (MOMS): A Phase II Randomized Comparison of Three Antiretroviral Strategies Administered for 7 or 21 Days to Reduce the Emergence of Nevirapine Resistant HIV-1 Following a Single Intrapartum Dose of Nevirapine
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 484
- Locations
- 8
- Primary Endpoint
- Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 13 Years to — (Child, Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
7-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
Intervention: Lamivudine/Zidovudine (Drug)
7-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
Intervention: single dose Nevirapine (Drug)
21-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
Intervention: Lamivudine/Zidovudine (Drug)
21-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
Intervention: single dose Nevirapine (Drug)
7-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
Intervention: Emtricitabine/Tenofovir Disoproxil Fumarate (Drug)
7-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
Intervention: single dose Nevirapine (Drug)
21-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
Intervention: Emtricitabine/Tenofovir Disoproxil Fumarate (Drug)
21-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
Intervention: single dose Nevirapine (Drug)
7-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
Intervention: Lopinavir/Ritonavir (Drug)
7-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
Intervention: single dose Nevirapine (Drug)
21-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Intervention: Lopinavir/Ritonavir (Drug)
21-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Intervention: single dose Nevirapine (Drug)
Outcomes
Primary Outcomes
Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
Time Frame: 2 and 6 weeks after completion of treatment
For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint. 10 participants who did not have resistance samples available were excluded from the primary endpoint analysis.
Secondary Outcomes
- Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.(2 and 6 weeks after completion of treatment)
- Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.(2 and 6 weeks after completion of treatment)
- Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12(From first day of study treatment to week 12)
- Number of Participants Who Discontinued Study Treatment Prematurely(From first day of study treatment to last day of study treatment (up to 21 days))