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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Emtricitabine/Tenofovir Disoproxil Fumarate
* Drug: Lamivudine/Zidovudine
* Drug: Lopinavir/Ritonavir
* Drug: single dose Nevirapine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 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. | 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. | 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 | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Treatment Naive