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

Primary Purpose

HIV Infections

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Emtricitabine/Tenofovir Disoproxil Fumarate
Lamivudine/Zidovudine
Lopinavir/Ritonavir
single dose Nevirapine
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Treatment Naive

Eligibility Criteria

13 Years - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
  • Byramjee Jeejeebhoy Government Medical College CRS
  • Chennai Antiviral Research and Treatment (CART) CRS
  • Blantyre CRS
  • Wits Helen Joseph Hospital CRS (Wits HJH CRS)
  • Durban International CRS
  • Kilimanjaro Christian Medical CRS
  • Joint Clinical Research Center (JCRC)/Kampala CRS

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

7-day 3TC/ZDV

21-day 3TC/ZDV

7-day FTC/TDF

21-day FTC/TDF

7-day LPV/r

21-day LPV/r

Arm Description

SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.

SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.

SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.

SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.

SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.

SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r

Outcomes

Primary Outcome Measures

Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
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.
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.
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
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
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.

Full Information

First Posted
December 17, 2004
Last Updated
November 2, 2021
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00099632
Brief Title
Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
November 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
Treatment Naive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
484 (Actual)

8. Arms, Groups, and Interventions

Arm Title
7-day 3TC/ZDV
Arm Type
Experimental
Arm Description
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.
Arm Title
21-day 3TC/ZDV
Arm Type
Experimental
Arm Description
SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.
Arm Title
7-day FTC/TDF
Arm Type
Experimental
Arm Description
SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.
Arm Title
21-day FTC/TDF
Arm Type
Experimental
Arm Description
SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.
Arm Title
7-day LPV/r
Arm Type
Experimental
Arm Description
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.
Arm Title
21-day LPV/r
Arm Type
Experimental
Arm Description
SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r
Intervention Type
Drug
Intervention Name(s)
Emtricitabine/Tenofovir Disoproxil Fumarate
Other Intervention Name(s)
FTC/TDF
Intervention Description
200mg/300mg as one tablet taken orally once daily
Intervention Type
Drug
Intervention Name(s)
Lamivudine/Zidovudine
Other Intervention Name(s)
3TC/ZDV
Intervention Description
150mg/300mg as one tablet taken orally twice daily
Intervention Type
Drug
Intervention Name(s)
Lopinavir/Ritonavir
Other Intervention Name(s)
LPV/r
Intervention Description
133.3mg/33.3mg as three capsules taken orally twice daily
Intervention Type
Drug
Intervention Name(s)
single dose Nevirapine
Other Intervention Name(s)
SD NVP
Intervention Description
one 200 mg tablet taken orally
Primary Outcome Measure Information:
Title
Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping
Description
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.
Time Frame
2 and 6 weeks after completion of treatment
Secondary Outcome Measure Information:
Title
Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.
Description
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.
Time Frame
2 and 6 weeks after completion of treatment
Title
Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.
Description
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.
Time Frame
2 and 6 weeks after completion of treatment
Title
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
Description
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
Time Frame
From first day of study treatment to week 12
Title
Number of Participants Who Discontinued Study Treatment Prematurely
Description
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.
Time Frame
From first day of study treatment to last day of study treatment (up to 21 days)

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
13 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jane Hitti, MD, MPH
Organizational Affiliation
Department of Obstetrics/Gynecology, Perinatal Medicine, University of Washington Medical Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Deborah McMahon, MD
Organizational Affiliation
Division of Infectious Diseases, Department of Medicine, University of Pittsburgh
Official's Role
Study Chair
Facility Information:
Facility Name
Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS
City
Port-au-Prince
ZIP/Postal Code
6110
Country
Haiti
Facility Name
Byramjee Jeejeebhoy Government Medical College CRS
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411001
Country
India
Facility Name
Chennai Antiviral Research and Treatment (CART) CRS
City
Chennai
State/Province
Tamil Nadu
ZIP/Postal Code
600113
Country
India
Facility Name
Blantyre CRS
City
Blantyre
Country
Malawi
Facility Name
Wits Helen Joseph Hospital CRS (Wits HJH CRS)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Facility Name
Durban International CRS
City
Westville
State/Province
KwaZulu-Natal
ZIP/Postal Code
3610
Country
South Africa
Facility Name
Kilimanjaro Christian Medical CRS
City
Moshi
Country
Tanzania
Facility Name
Joint Clinical Research Center (JCRC)/Kampala CRS
City
Kampala
Country
Uganda

12. IPD Sharing Statement

Citations:
PubMed Identifier
12134253
Citation
Cunningham CK, Chaix ML, Rekacewicz C, Britto P, Rouzioux C, Gelber RD, Dorenbaum A, Delfraissy JF, Bazin B, Mofenson L, Sullivan JL. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis. 2002 Jul 15;186(2):181-8. doi: 10.1086/341300. Epub 2002 Jun 26.
Results Reference
background
PubMed Identifier
12152519
Citation
Eshleman SH, Jackson JB. Nevirapine resistance after single dose prophylaxis. AIDS Rev. 2002 Apr-Jun;4(2):59-63.
Results Reference
background
PubMed Identifier
15247339
Citation
Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
15627034
Citation
Lyons FE, Coughlan S, Byrne CM, Hopkins SM, Hall WW, Mulcahy FM. Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy. AIDS. 2005 Jan 3;19(1):63-7. doi: 10.1097/00002030-200501030-00007. Erratum In: AIDS. 2007 Jul 31;21(12):1671.
Results Reference
background
PubMed Identifier
14562860
Citation
Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. doi: 10.1097/00126334-200309011-00010.
Results Reference
background
Citation
McMahon D, Noel F, Zheng L, Kabanda J, Halvas E, Taulo F, Kumarasamy N, Wallis C, Hughes M, Mellors J. Suppression of NVP Resistance with 7- vs 21-day ARV Regimens after Single-dose NVP: Results of A5207. Presented at 18th Conference on Retroviruses & Opportunistic Infections (CROI 11) on 03/01/2011 at Boston, MA
Results Reference
result
Citation
Hong F, Halvas E, Chan E, Zheng L, Hughes M, Hitti J, McMahon D, Mellors J. Suppression of Minor NVP-Resistant Variants With 7- vs. 21-Day Antiretroviral Regimens After Single Dose Nevirapine. Presented at 20th Anniversary of the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies on Jun 9, 2011, Los Cabos, Mexico
Results Reference
result
PubMed Identifier
23300238
Citation
McMahon DK, Zheng L, Hitti J, Chan ES, Halvas EK, Hong F, Kabanda J, Taulo F, Kumarasamy N, Bonhomme J, Wallis CL, Klingman KL, Hughes MD, Mellors JW. Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV. Clin Infect Dis. 2013 Apr;56(7):1044-51. doi: 10.1093/cid/cis1219. Epub 2013 Jan 8.
Results Reference
derived

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

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