Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 28 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01618305
First received: June 6, 2012
Last updated: July 21, 2015
Last verified: July 2015
  Purpose

HIV-infected pregnant women who begin taking antiretroviral (ARV) medications in the late stages of pregnancy need an effective medication regimen to reduce the risk of transmitting HIV to their children. This study will examine the virologic response, safety, and tolerability of two different ARV medication regimens in HIV-infected pregnant women who are between 28 and 36 weeks pregnant when they enter the study.


Condition Intervention Phase
HIV Infections
Drug: Lamivudine/zidovudine
Drug: Efavirenz
Drug: Raltegravir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: A Phase IV Randomized Trial to Evaluate the Virologic Response and Pharmacokinetics of Two Different Potent Regimens in HIV Infected Women Initiating Triple Antiretroviral Regimens Between 28 and 36 Weeks of Pregnancy for the Prevention of Mother-to-Child Transmission: NICHD P1081

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Plasma HIV-1 viral load less than 200 copies/mL [ Time Frame: Measured at participants' delivery visit (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
    If there is no viral load measurement at the delivery visit, viral load less than 200 copies/mL within 3 weeks prior to delivery.

  • Number of participants who discontinue efavirenz or raltegravir (whichever was assigned) prior to labor and delivery for any reason (including loss to follow-up) [ Time Frame: Measured up to participants' delivery visit (approximately 36 to 40 weeks) ] [ Designated as safety issue: Yes ]
  • Maternal adverse events of greater than or equal to Grade 3 as defined in the Division of AIDS (DAIDS) toxicity table [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: Yes ]
  • Infant adverse events of greater than or equal to Grade 3 as defined in the DAIDS toxicity table [ Time Frame: Measured through infants' last study visit at Week 24 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Virologic suppression to below the lower limit of quantification of the assay [ Time Frame: Measured at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • Number of participants with 1) successful viral load (plasma HIV-1 RNA VL) decrease from entry to Week 2 and VL less than 1,000 copies/ml at all time points after 4 weeks on study drugs, until delivery; and 2) who remain on the assigned study regimen [ Time Frame: Measured through delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: Yes ]
  • Viral load in maternal blood [ Time Frame: Measured through Week 6 after starting treatment ] [ Designated as safety issue: No ]
  • Viral load in maternal vaginal swabs [ Time Frame: Measured through Week 6 after starting treatment ] [ Designated as safety issue: No ]
  • Log10 change in viral load from entry (or screening, if there is no entry viral load) to each time point prior to delivery [ Time Frame: Measured through participants' study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • Infectivity of plasma [ Time Frame: Measured during the initial 2 weeks of ARV therapy ] [ Designated as safety issue: No ]
  • Number of participants who experience a stillbirth/fetal demise [ Time Frame: Measured through participants' last study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • Number of participants who experience a premature birth (less than 34 or less than 37 weeks gestation) [ Time Frame: Measured through participants' last study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • Number of infants with a low birth weight (less than 1500 or less than 2500 grams) [ Time Frame: Measured through participants' last study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • Infant HIV infection status (per International Maternal Pediatric Adolescent AIDS Clinical Trials Group [IMPAACT] definitions) [ Time Frame: Measured through infants' last study visit at Week 24 ] [ Designated as safety issue: No ]
  • Measurements of infant IQ scores (from the Bayley and Wechsler scales) [ Time Frame: Measured through infants' last study visit at Year 4 ] [ Designated as safety issue: No ]
  • Measurements of infant executive functioning skills (from the BRIEF questionnaire) [ Time Frame: Measured through infants' last study visit at Year 4 ] [ Designated as safety issue: No ]
  • Measurements of infant neurodevelopmental deficits (from the Ten Questions Questionnaire and the Ages and Stages Questionnaire) [ Time Frame: Measured through infants' last study visit at Year 4 ] [ Designated as safety issue: No ]
  • Incidence of drug resistance in HIV-infected infants [ Time Frame: Measured through infants' last study visit at Week 24 ] [ Designated as safety issue: No ]
  • HIV-1 drug resistance mutations at screening, at 2-4 weeks postpartum in women who have stopped antiretroviral therapy, and at the time of inadequate virologic response (defined in the protocol) using standard and ultrasensitive genotyping methods [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]

Estimated Enrollment: 394
Study Start Date: July 2013
Estimated Primary Completion Date: June 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm A

Participants will receive lamivudine 150 mg/zidovudine 300 mg* twice a day and efavirenz 600 mg each night.

* Participants may receive a locally supplied nucleoside reverse transcriptase inhibitor (NRTI) backbone in place of lamivudine/zidovudine with permission of the protocol team obtained prior to randomization.

Drug: Lamivudine/zidovudine
Participants will receive one lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet twice a day.
Drug: Efavirenz
Participants will receive one 600 mg tablet of efavirenz each night.
Experimental: Arm B

Participants will receive lamivudine 150 mg/zidovudine 300 mg* twice a day and raltegravir 400 mg twice a day.

* Participants may receive a locally supplied nucleoside reverse transcriptase inhibitor (NRTI) backbone in place of lamivudine/zidovudine with permission of the protocol team obtained prior to randomization.

Drug: Lamivudine/zidovudine
Participants will receive one lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet twice a day.
Drug: Raltegravir
Participants will receive one 400 mg raltegravir tablet twice a day.

Detailed Description:

While there are many ARV medications and combination regimens available to treat HIV-infected people, the number of ARV medications studied in HIV-infected pregnant women for the prevention of mother-to-child transmission remains limited. HIV-infected pregnant women who begin taking ARV medications late in their pregnancies require effective therapy to reduce the risk of transmitting HIV to their children. Currently, there is no data available that compares the effects of non-nucleoside reverse transcriptase inhibitors (NNRTI) and integrase inhibitors (which are two classes of ARV medications) in pregnant women. The purpose of this study is to compare the safety, tolerance, and virologic and pharmacologic responses to two different medication regimens, each including an NNRTI or integrase inhibitor, in pregnant HIV-infected women who begin ARV therapy late in their pregnancies (i.e., a gestational age between 28 and 36 weeks).

Participants in this study will be randomly assigned to one of two arms. Participants in Arm A will receive lamivudine 150 mg/zidovudine 300 mg twice a day and efavirenz 600 mg each night. Participants in Arm B will receive lamivudine 150 mg/zidovudine 300 mg twice a day and raltegravir 400 mg twice a day. All participants will receive their assigned medications from study entry through delivery. Participants will attend study visits at entry and Weeks 1, 2, and 4; and thereafter, every two weeks until labor and delivery. Study visits will include a medical history review, physical examination, questionnaires, blood collection, and a vaginal swab procedure.

While participants are in labor, they will continue to receive their study medications. Some participants may receive additional or alternate medications according to local standard of care/guidelines. Participants will have a physical examination and blood collection. After delivery, some women will continue to receive ARV medications according to the local guidelines. Participants will attend study visits following the delivery at Weeks 2 to 4, 6, 16, and 24, which will include a medical history review, physical examination, and blood collection. One study visit will include a vaginal swab procedure. Some participants may have vaginal specimens stored for future research.

Participants' babies will receive ARV medications as prescribed by the babies' doctors. Study visits for babies will occur at birth; Weeks 2 to 4, 6, 16, and 24. Each study visit will include a medical history review, physical examination, and blood collection. Select visits will include oral and nasopharyngeal swab collection. Some babies will be followed for up to 4 years of age as part of an optional neurodevelopmental assessment substudy.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Naive to antiretroviral therapy (ART) or have received ART with short course zidovudine (maximum of 8 weeks) for prevention of mother-to-child transmission in previous pregnancies
  • Willing and able to sign informed consent. Participant must be of an age to provide legal informed consent as defined by the country in which the participant resides. If not, the informed consent must be signed by a legal guardian/parent, as per country guidelines.
  • Documentation of HIV-1 infection defined as positive results from two samples collected at different time points. The same method may be used at both time points. All samples tested must be whole blood, serum, or plasma. Documentation may be abstracted from medical records to satisfy these criteria for infection. More information on this criterion can be found in the protocol.
  • Viable pregnancy with gestational age of greater than or equal to 28 weeks to less than or equal to 36 weeks based upon menstrual history and/or ultrasound. Note: If menstrual history is unknown or if there is a discrepancy between menstrual history and ultrasound, determination of gestational age should be based upon best available methodology at each site.
  • Intends to continue pregnancy
  • Willingness and intent to deliver at the participating clinical site and to be followed for the duration of the study at the site or associated outpatient facility
  • Willing to comply with the study regimen
  • Agrees to use two reliable methods of contraception after delivery if randomized to the efavirenz arm and is sexually active. A barrier method of contraception (condoms, diaphragm, or cervical cap) together with another reliable form of contraception must be used for 4 weeks after stopping efavirenz.

Exclusion Criteria:

  • Active labor defined as onset of regular contractions or cervical dilatation greater than 2 cm
  • Use of ART during current pregnancy
  • Chemotherapy for active malignancy
  • HIV genotypic resistance, as defined in the protocol, to efavirenz or raltegravir or to NRTIs that will be included in the ART regimen. Note: A lack of HIV drug resistance test results at the time of enrollment is not exclusionary.
  • Serious active opportunistic infection and/or serious bacterial infection including active tuberculosis (TB) or unstable or severe medical condition within 14 days of study entry
  • Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
  • Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise the outcome of this study
  • Vomiting or inability to swallow medications due to an active, pre-existing condition that prevents adequate swallowing and absorption of study medication
  • Known allergy/sensitivity to any study drugs or their formulations or sulfonamide allergy
  • The following laboratory values (within 30 days of enrollment):

    1. Hemoglobin greater than or equal to Grade 3
    2. Absolute neutrophil count greater than or equal to Grade 2
    3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to Grade 2
    4. Serum creatinine greater than or equal to Grade 1
    5. Platelet count greater than or equal to Grade 3
  • Evidence of pre-eclampsia (such as persistent diastolic blood pressure greater than 90 mm Hg)
  • Receipt of disallowed medications as described in the protocol
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01618305

  Show 36 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Esau Joao, M.D. Hospital Federal dos Servidores do Estado - RJ
Study Chair: Mark Mirochnick, M.D. Boston Medical Center
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01618305     History of Changes
Other Study ID Numbers: P1081, 10770, IMPAACT P1081
Study First Received: June 6, 2012
Last Updated: July 21, 2015
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Efavirenz
Lamivudine
Lamivudine, zidovudine drug combination
Reverse Transcriptase Inhibitors
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antimetabolites
Antiviral Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on August 30, 2015