HIV Treatment Reinitiation in Women Who Received Anti-HIV Drugs to Prevent Mother-to-Child Transmission of HIV

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate

• Registration Number: NCT00442962
• Lead Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

Brief Summary

The purpose of this study is to determine if pregnancy-limited, short-term combination HIV treatment regimens -- which were used solely for the prevention of mother to child transmission of HIV and discontinued postpartum -- decreases the effectiveness of a standard initial regimen of anti-HIV drugs when subsequent treatment is needed.

Detailed Description

Stopping and restarting highly active antiretroviral therapy (HAART) is not generally recommended because it has the potential to allow drug-resistant HIV to emerge. However, to prevent mother-to-child transmission (MTCT), HIV infected women who are pregnant are temporarily put on HAART, even if HIV treatment is not indicated at the time. It is unknown if such short-term therapy affects the viral response to HAART later, when permanent therapy is clinically indicated. The purpose of this study is to determine if HAART taken to prevent MTCT during pregnancy has an effect on the ability of a standard initial regimen of HAART to suppress HIV viral load.\> \>\>

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\>\> Study follow-up will last for 48 weeks per participant. Participants will take a daily regimen of efavirenz and emtricitabine/tenofovir disoproxil fumarate. There will be 8 clinical visits in this study; visits will occur at baseline and at Weeks 2, 4, 8, 16, 24, 36, and 48. At each visit, a physical exam, blood and urine collection, and pregnancy tests will occur. At some visits, adherence, quality-of-life, and birth control interviews will be completed.\>

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\>\> Enrollment in this study will last until 47 participants have joined or until December 31, 2009, whichever comes later.

Study Timeline

• Study First Submitted: 2007-03-02
• Study First Submitted QC: 2007-03-02
• Study First Posted: 2007-03-05
• Study Start: 2007-05
• Primary Completion: 2010-07
• Study Completion: 2010-12
• Results First Submitted: 2011-07-13
• Results First Submitted QC: 2011-07-13
• Results First Posted: 2011-08-09
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-11
• Last Update Posted: 2018-10-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 54

Inclusion Criteria

• HIV-1 infected
• Viral load of 500 copies/mL or more
• Prior HAART for more than 7 days, but less than 40 weeks during at least one previous pregnancy for prevention of MTCT of HIV
• Clinical or laboratory indication to start HAART, in the opinion of the participant's physician
• Certain laboratory values
• Willingness to use acceptable forms of contraception
• Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria

• Taking any antiretroviral medication within 24 weeks prior to study entry
• Evidence of certain HIV-1 RT mutations within 90 days prior to study entry (version 1.0)
• Evidence of certain HIV-1 RT mutations identified by standard bulk viral population genotypic resistance tests at any time prior to study entry, if available (version 2.0, 09/03/2009)
• Treatment at any time, for any reason with nevirapine as a single agent OR addition of any part of the study regimen as a single agent to a failing regimen
• Use of certain antihistamines, certain anti-infectives, cisapride, St John's wort, midazolam, triazolam, dihydroergotamine, ergonovine, ergotamine, or methylergonovine within 14 days prior to study entry
• Use of HIV vaccine, chronic systemic corticosteroids, interleukins, interferons, other cytokines, or investigational therapy within 30 days prior to study entry
• Acute or chronic therapy for certain serious medical illnesses within 14 days of study entry. Participants who have completed 7 days of therapy and are judged clinically stable are not excluded.
• Cancer requiring systemic chemotherapy
• Known allergy/sensitivity to the study drugs or their formulations
• Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study
• Two consecutive HIV viral loads of more than 5,000 copies/mL 8 weeks or more following initiation of HAART during pregnancy and while still receiving HAART
• Two consecutive viral loads of more than 400 copies/mL 24 weeks or more following initiation of HAART during pregnancy while still receiving HAART
• Current imprisonment or involuntary incarceration in a medical facility for psychiatric or physical illness
• Pregnancy or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
EFV + FTC/TDF	Emtricitabine/Tenofovir disoproxil fumarate	Participants will efavirenz (600mg in pill form, taken orally, once daily) and emtricitabine/tenofovir disoproxil fumarate (200/300mg in pill form, taken orally, once daily), for 48 weeks
EFV + FTC/TDF	Efavirenz	Participants will efavirenz (600mg in pill form, taken orally, once daily) and emtricitabine/tenofovir disoproxil fumarate (200/300mg in pill form, taken orally, once daily), for 48 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Early Virologic Response	At Week 24	Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml

Secondary Outcome Measures

Name	Time	Method
Time to Initial Virologic Response	Throughout study	Time from enrollment to scheduled week of first plasma HIV-1 RNA viral load fewer than 400 copies/mL.
Percentage of Participants With Early Virologic Suppression	At Weeks 24	Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml
Percentage of Participants With Late Virologic Response	At Week 48	Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml
Time to First Safety Event	Throughout study	Time from starting study treatment to first grade 3 or 4 sign/symptom or laboratory abnormality and at least one grade higher than baseline. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables.
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm)	Throughout study
Time to Initial Virological Failure	Throughout study	Virologic failure defined as two consecutive measurements of plasma HIV-1 RNA at least 400 copies/mL at or after the week 16 study visit. Time measured from enrollment.
Percentage of Participants With Late Virologic Suppression	At Week 48	Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml
Time to First Dose Modification	Throughout study	Time from starting study treatment to first dose/drug modification.
Late Change in CD4 Count From Baseline	At week 48	Change in CD4+ lymphocyte counts between week 48 study visit and baseline.
Early Changes in CD4 Count From Baseline	At weeks 0(baseline), 4, 8, 16, 24	Changes in CD4+ lymphocyte counts between study visit weeks 4, 8 16 and 24 and baseline.

Trial Locations

Locations (9)

Ucsd, Avrc; 🇺🇸 San Diego, California, United States

Brigham and Women's Hospital, Division of Infectious Disease; 🇺🇸 Boston, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Bronx-Lebanon Hosp. Ctr. CRS; 🇺🇸 Bronx, New York, United States

Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea; 🇺🇸 New York, New York, United States

San Miguel CRS; 🇵🇪 San Miguel, Lima, Peru

Barranco CRS; 🇵🇪 Lima, Peru

Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Fundacao Oswaldo Cruz; 🇧🇷 Rio de Janeiro, Brazil

University of North Carolina; 🇺🇸 Chapel Hill, North Carolina, United States