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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00099632
First received: December 17, 2004
Last updated: August 12, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
Drug: Lamivudine/Zidovudine
Drug: Lopinavir/Ritonavir
Drug: single dose Nevirapine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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 Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: Yes ]

    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


  • 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) ] [ Designated as safety issue: No ]
    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.


Enrollment: 484
Study Start Date: March 2006
Study Completion Date: November 2011
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 3TC/ZDV
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: 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 Name: 3TC/ZDV
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: 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: Emtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
Other Name: FTC/TDF
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: SD NVP
Experimental: 21-day FTC/TDF
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
200mg/300mg as one tablet taken orally once daily
Other Name: FTC/TDF
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: SD NVP
Experimental: 7-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
Drug: Lopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
Other Name: LPV/r
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: SD NVP
Experimental: 21-day LPV/r
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Drug: Lopinavir/Ritonavir
133.3mg/33.3mg as three capsules taken orally twice daily
Other Name: LPV/r
Drug: single dose Nevirapine
one 200 mg tablet taken orally
Other Name: SD NVP

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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099632

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00099632     History of Changes
Other Study ID Numbers: A5207, 10127, ACTG A5207, MOMS
Study First Received: December 17, 2004
Results First Received: December 6, 2011
Last Updated: August 12, 2014
Health Authority: United States: Food and Drug Administration
United States: Data and Safety Monitoring Board

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Lamivudine
Tenofovir
Tenofovir disoproxil
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 25, 2014