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

The Effect of Prior Short Course Combination Antiretroviral Therapy Administered for the Prevention of Mother-to-Child Transmission (pMTCT) of HIV-1 on Subsequent Treatment Efficacy in Treatment-"Nearly Naive" Participants

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Efavirenz; Drug: Emtricitabine/Tenofovir disoproxil fumarate

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 Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 4

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21045
    • Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Fundacao Oswaldo Cruz
• Peru
  • Lima, Peru, 18
    • Barranco CRS
  • Lima
    • San Miguel, Lima, Peru
      • San Miguel CRS
• United States
  • California
    • San Diego, California, United States, 92103
      • Ucsd, Avrc
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital, Division of Infectious Disease
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Washington University School of Medicine
  • New York
    • Bronx, New York, United States, 10457
      • Bronx-Lebanon Hosp. Ctr. CRS
    • New York, New York, United States, 10011
      • Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EFV + FTC/TDF; 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	Drug: Efavirenz; 600-mg tablet taken orally daily; Other Names: EFV; Drug: Emtricitabine/Tenofovir disoproxil fumarate; 200-mg emtricitabine/300-mg tenofovir disoproxil fumarate tablet taken orally once daily; Other Names: Truvada

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Early Virologic Response	Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml	At Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Safety Event	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.	Throughout study
Percentage of Participants With Early Virologic Suppression	Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml	At Weeks 24
Percentage of Participants With Late Virologic Response	Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml	At Week 48
Time to Initial Virologic Response	Time from enrollment to scheduled week of first plasma HIV-1 RNA viral load fewer than 400 copies/mL.	Throughout study
Time to Initial Virological Failure	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.	Throughout study
Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm)		Throughout study
Early Changes in CD4 Count From Baseline	Changes in CD4+ lymphocyte counts between study visit weeks 4, 8 16 and 24 and baseline.	At weeks 0(baseline), 4, 8, 16, 24
Percentage of Participants With Late Virologic Suppression	Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml	At Week 48
Time to First Dose Modification	Time from starting study treatment to first dose/drug modification.	Throughout study
Late Change in CD4 Count From Baseline	Change in CD4+ lymphocyte counts between week 48 study visit and baseline.	At week 48

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Mary A. Vogler, MD, Division of Infectious Diseases, Weill College of Medicine of Cornell University

Publications and helpful links

General Publications

• Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43.
• Bassetti D, Cargnel A. Genotypic resistance tests for the management of the HIV-infected pregnant woman. Scand J Infect Dis Suppl. 2003;106:70-4.
• Duran AS, Losso MH, Salomon H, Harris DR, Pampuro S, Soto-Ramirez LE, Duarte G, de Souza RS, Read JS; NISDI Perinatal Study Group. Drug resistance among HIV-infected pregnant women receiving antiretrovirals for prophylaxis. AIDS. 2007 Jan 11;21(2):199-205. doi: 10.1097/QAD.0b013e328011770b.

Helpful Links

• Click here for more information on this network of studies

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): July 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: March 2, 2007
• First Submitted That Met QC Criteria: March 2, 2007
• First Posted (Estimate): March 5, 2007

Study Record Updates

• Last Update Posted (Actual): October 12, 2018
• Last Update Submitted That Met QC Criteria: September 11, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors; Tenofovir; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz
• Other Study ID Numbers: ACTG A5227; 1U01AI068636 (U.S. NIH Grant/Contract)