Clinical trial NCT00442962: HIV Treatment Reinitiation in Women Who Received Anti-HIV Drugs to Prevent Mother-to-Child Transmission of HIV
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Lead sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Sponsor class: NETWORK
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2007-03-05
Enrollment: 54
Sex: FEMALE
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants With Early Virologic Response
timeFrame: At Week 24
Secondary outcomes:
measure: Time to First Safety Event
timeFrame: Throughout study
measure: Percentage of Participants With Early Virologic Suppression
timeFrame: At Weeks 24
measure: Percentage of Participants With Late Virologic Response
timeFrame: At Week 48
measure: Time to Initial Virologic Response
timeFrame: Throughout study
measure: Time to Initial Virological Failure
timeFrame: Throughout study
measure: Time to Loss of Virologic Response by Week 48 (Defined by FDA TLOVR Algorithm)
timeFrame: Throughout study
measure: Early Changes in CD4 Count From Baseline
timeFrame: At weeks 0(baseline), 4, 8, 16, 24
measure: Percentage of Participants With Late Virologic Suppression
timeFrame: At Week 48
measure: Time to First Dose Modification
timeFrame: Throughout study
measure: Late Change in CD4 Count From Baseline
timeFrame: At week 48
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Ucsd, Avrc
state: California
city: Boston
country: United States
facility: Brigham and Women's Hospital, Division of Infectious Disease
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp. Ctr. CRS
state: New York
city: New York
country: United States
facility: Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Rio de Janeiro
country: Brazil
facility: Instituto de Pesquisa Clinica Evandro Chagas Fiocruz, Fundacao Oswaldo Cruz
city: San Miguel
country: Peru
facility: San Miguel CRS
state: Lima
city: Lima
country: Peru
facility: Barranco CRS
Study officials:
affiliation: Division of Infectious Diseases, Weill College of Medicine of Cornell University
name: Mary A. Vogler, MD
role: STUDY_CHAIR
References:
citation: Abrams EJ. Prevention of mother-to-child transmission of HIV--successes, controversies and critical questions. AIDS Rev. 2004 Jul-Sep;6(3):131-43.
citation: 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.
citation: 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.