Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy

November 2, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

484

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Haiti
      • Port-au-Prince, Haiti, 6110
        • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
  • India
    • Maharashtra
      • Pune, Maharashtra, India, 411001
        • Byramjee Jeejeebhoy Government Medical College CRS
    • Tamil Nadu
      • Chennai, Tamil Nadu, India, 600113
        • Chennai Antiviral Research and Treatment (CART) CRS
  • Malawi
      • Blantyre, Malawi
        • Blantyre CRS
  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2092
        • Wits Helen Joseph Hospital CRS (Wits HJH CRS)
    • KwaZulu-Natal
      • Westville, KwaZulu-Natal, South Africa, 3610
        • Durban International CRS
  • Tanzania
      • Moshi, Tanzania
        • Kilimanjaro Christian Medical CRS
  • Uganda
      • Kampala, Uganda
        • Joint Clinical Research Center (JCRC)/Kampala CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria for Mothers:

  • HIV-1 infected
  • CD4 count 250 cells/mm3 or greater within 30 days of study entry
  • The following laboratory values obtained within 30 days prior to study entry: absolute neutropil count >= 750/mm3; hemoglobin >= 8.0 g/dL; platelet count >= 50,000/mm3; calculated creatinine clearance (Cockcroft-Gault formula) > 60 mL/min; AST(SGOT) and ALT(SGPT) < 5 x ULN; total bilirubin < 1.5 X ULN.
  • Pregnant with a viable fetus at 28 to 38 weeks gestation at study entry.
  • Willing to give birth to baby in a hospital or clinic
  • Written informed consent from parent or guardian, if applicable

Exclusion Criteria for Mothers:

  • Any ART, including single-dose NVP, prior to study entry. Mothers who receive ZDV monotherapy prior to labor under the supervision of the site investigator are not excluded.
  • Known allergy or sensitivity to study drugs or their formulations
  • Current drug or alcohol abuse that may interfere with the study
  • Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.
  • Hepatitis B surface antigen positive within 180 days prior to study entry
  • Active tuberculosis infection requiring treatment
  • Prior enrollment in this study
  • Expect to use ART, except ZDV monotherapy, prior to onset of labor
  • Expect to use ART other than study medications from delivery to 9 weeks postpartum

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 7-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
Drug: Lamivudine/Zidovudine
150mg/300mg as one tablet taken orally twice daily
Other Names:
  • 3TC/ZDV
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Experimental: 21-day 3TC/ZDV
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
Drug: Lamivudine/Zidovudine
150mg/300mg as one tablet taken orally twice daily
Other Names:
  • 3TC/ZDV
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Experimental: 7-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
Other Names:
  • FTC/TDF
Experimental: 21-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
Other Names:
  • FTC/TDF
Experimental: 7-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Drug: Lopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
Other Names:
  • LPV/r
Experimental: 21-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Names:
  • SD NVP
Drug: Lopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
Other Names:
  • LPV/r

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
2 and 6 weeks after completion of treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With New Circulating NRTI-resistant Variants 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; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
2 and 6 weeks after completion of treatment
Number of Participants With New PI-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; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed.
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
Time Frame: From first day of study treatment to week 12

Grade 3 or higher signs and symptoms, laboratory abnormalities, events that are reported through the EAE system, and any grade event that leads to a treatment change from first day of study treatment to week 12.

Grade 3 = Severe Grade 4 = Life threatening Grade 5 = Death
From first day of study treatment to week 12
Number of Participants Who Discontinued Study Treatment Prematurely
Time Frame: From first day of study treatment to last day of study treatment (up to 21 days)
participants assigned to 7-day treatment arm and 21-day treatment arm were supposed to stay in study treatment for 7 days and 21 days respectively.
From first day of study treatment to last day of study treatment (up to 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Jane Hitti, MD, MPH, Department of Obstetrics/Gynecology, Perinatal Medicine, University of Washington Medical Center
  • Study Chair: Deborah McMahon, MD, Division of Infectious Diseases, Department of Medicine, University of Pittsburgh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2006

Primary Completion (Actual)

April 1, 2010

Study Completion (Actual)

November 1, 2011

Study Registration Dates

First Submitted

December 17, 2004

First Submitted That Met QC Criteria

December 17, 2004

First Posted (Estimate)

December 20, 2004

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

November 2, 2021

Last Verified

January 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5207
  • MOMS
  • 10127 (Registry Identifier: DAIDS ES)
  • ACTG A5207

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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