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

• Time to First Safety Event [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  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.
• Percentage of Participants With Early Virologic Suppression [ Time Frame: At Weeks 24 ] [ Designated as safety issue: No ]
  Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml
• Percentage of Participants With Late Virologic Response [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
  Plasma HIV-1 Viral Load Fewer Than 400 Copies/ml
• Time to Initial Virologic Response [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  Time from enrollment to scheduled week of first plasma HIV-1 RNA viral load fewer than 400 copies/mL.
• Time to Initial Virological Failure [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  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.
• Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
• Early Changes in CD4 Count From Baseline [ Time Frame: At weeks 0(baseline), 4, 8, 16, 24 ] [ Designated as safety issue: No ]
  Changes in CD4+ lymphocyte counts between study visit weeks 4, 8 16 and 24 and baseline.
• Percentage of Participants With Late Virologic Suppression [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]
  Plasma HIV-1 Viral Load Fewer Than 50 Copies/ml
• Time to First Dose Modification [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  Time from starting study treatment to first dose/drug modification.
• Late Change in CD4 Count From Baseline [ Time Frame: At week 48 ] [ Designated as safety issue: No ]
  Change in CD4+ lymphocyte counts between week 48 study visit and baseline.

• Safety and tolerability of efavirenz (EFV) and emtricitabine/tenofovir disproxil fumarate (FTC/TDF) regimen
• virologic suppression at Weeks 24 and 48
• virologic response at Week 48
• time to initial virologic response and suppression
• time to initial virological failure
• time to loss of virological response
• presence of drug-resistant minority variants present at baseline
• plasma concentrations of EFV, FTC, and TDF
• CD4 counts and changes from baseline
• adherence to drug regimen
• quality-of-life score

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.

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.

• Drug: Efavirenz
  600-mg tablet taken orally daily
  Other Name: EFV
• Drug: Emtricitabine/Tenofovir disoproxil fumarate
  200-mg emtricitabine/300-mg tenofovir disoproxil fumarate tablet taken orally once daily
  Other Name: Truvada

• 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 Dec;35 Suppl 106:70-4. Review.
• 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.

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