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

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

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Efavirenz
* Drug: Emtricitabine/Tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 16 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |