Trial record 6 of 519 for:    (pregnancy OR maternal) AND hiv

Evaluating the Response to Three 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 August 2014 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: August 18, 2014
Last verified: August 2014
  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 safety and immune response to three 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: Lopinavir/ritonavir
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 Three 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Rapid viral load decrease (sustained until delivery) [ Time Frame: Measured through participants' study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
    Composite binary outcome measure of (1) a successful viral load (plasma HIV-1 RNA) decrease from entry to study Week 2 (Day 11-17) and viral load less than 1,000 copies/mL at all timepoints after 4 weeks on study drugs, until delivery; and (2) tolerability (remaining on the assigned study regimen).

  • Tolerability of study drugs [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
    Discontinuation of one or more of the assigned study drugs prior to delivery for any reason (including loss to follow-up) will be considered a treatment failure in the efficacy analyses, except that switching only zidovudine to investigator-selected locally available nucleoside reverse transcriptase inhibitors (NRTIs) with continuation of the other two study drugs will not be considered a treatment failure. All women who received at least one dose of study drug will be evaluable for the tolerability component of the composite outcome measure.

  • Maternal adverse events of greater than or equal to Grade 3 as defined in the Division of AIDS (DAIDS) toxicity table and events of any grade that lead to discontinuation of one or more of the assigned study drugs [ 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 Year 4 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Virologic suppression to less than 200 copies/mL [ Time Frame: Measured at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • 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 ]
  • Infectivity of plasma [ Time Frame: Measured during the initial 2 weeks of ARV therapy ] [ Designated as safety issue: No ]
    The ratio of virion infectivity to HIV-1 RNA level will be compared between study arms. Collection of samples for virion infectivity assays and the Day 3 visit will only be done until 15 women in each of the three arms (45 women total) with plasma HIV RNA greater than 20,000 copies/mL at entry have been enrolled into this sub-study and have provided all required samples.

  • Log10 change in viral load from entry 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 ]
  • Viral load in maternal blood and vaginal secretions [ Time Frame: Measured at entry, Week 2, and near delivery ] [ 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 ]
  • Maternal Tregs, Tacts, inflammatory and regulatory cytokines and biomarkers [ Time Frame: Measured at enrollment and prior to delivery (36 to 38 weeks gestation) ] [ Designated as safety issue: No ]
  • Infant inflammatory and regulatory cytokines and biomarkers, and innate (NK) and adaptive immune responses (cell-mediated and antibody responses to vaccines) [ Time Frame: Measured at Weeks 2-4, 16, and 52 ] [ Designated as safety issue: No ]
  • Number of participants who experience a stillbirth [ 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 32 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 Year 4 ] [ 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 Year 4 ] [ Designated as safety issue: No ]
  • Measurement of population CL/F [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Measurement of population V/F [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Measurement of population t 1/2 [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Individual predicted empiric Bayesian CL/F [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Individual predicted empiric Bayesian V/F [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Individual predicted empiric Bayesian t 1/2 [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Individual predicted empiric Bayesian steady-state pre-dose concentrations [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Individual predicted empiric Bayesian area under the curve (AUC) [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • Cord-to-maternal plasma concentration ratio [ Time Frame: Measured through participants' study visit at delivery (approximately 36 to 40 weeks) ] [ Designated as safety issue: No ]
  • ARV concentrations in vaginal secretions [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]
  • ARV concentrations in plasma [ Time Frame: Measured through participants' last study visit 24 weeks after giving birth ] [ Designated as safety issue: No ]

Estimated Enrollment: 558
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 lopinavir 600 mg/ritonavir 150 mg twice a day.
Drug: Lamivudine/zidovudine
Participants will receive one lamivudine 150 mg/zidovudine 300 mg fixed-dose combination tablet twice a day.
Drug: Lopinavir/ritonavir
Participants will receive three lopinavir 200 mg/ritonavir 50 mg fixed-dose combination tablets twice a day.
Experimental: Arm B
Participants will receive lamivudine 150 mg/zidovudine 300 mg twice a day and efavirenz 600 mg each night.
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 C
Participants will receive lamivudine 150 mg/zidovudine 300 mg twice a day and raltegravir 400 mg twice a day.
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), protease inhibitors (PIs), and integrase inhibitors (which are three classes of ARV medications) in women who begin taking ARV medications late in their pregnancies. The purpose of this study is to compare the safety, tolerance, and virologic and immunologic responses to three different medication regimens, each including an NNRTI, PI, 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 three arms. Participants in Arm A will receive lamivudine 150 mg/zidovudine 300 mg twice a day and lopinavir 600 mg/ritonavir 150 mg twice a day. Participants in Arm B will receive lamivudine 150 mg/zidovudine 300 mg twice a day and efavirenz 600 mg each night. Participants in Arm C 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; Day 3; and Weeks 1, 2, 4, 6, and 36 to 38. Study visits will include a medical history review, physical examination, questionnaires, and blood collection. Some study visits will include a vaginal swab procedure.

While participants are in labor, they will receive intravenous zidovudine and oral lamivudine, along with the other medications they have been receiving. Participants will have a physical examination and blood collection, and study researchers will collect blood from the placenta and collect a sample of amniotic fluid from women having a cesarean delivery. 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; and Years 1, 2, 3, and 4. Each study visit will include a medical history review and physical examination. Select visits will include a blood collection and neurodevelopmental and neuropsychological evaluations.

  Eligibility

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

Inclusion Criteria:

  • Naive to ARV therapy or have received ARV therapy 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.
  • 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. More information on this criterion can be found in the protocol.
  • Viable singleton 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 normal fetal anatomy confirmed by ultrasound
  • 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 12 weeks after stopping efavirenz.

Exclusion Criteria:

  • Active labor defined as onset of regular contractions or cervical dilatation greater than 2 cm
  • Use of antiretroviral therapy during current pregnancy
  • Chemotherapy for active malignancy
  • Known HIV genotypic resistance to zidovudine, lamivudine, lopinavir, ritonavir, efavirenz, or raltegravir, as defined in the protocol. 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
  • Chronic malabsorption or chronic diarrhea (more than 6 loose stools/day for more than 14 days within 30 days of entry) or recent (within 7 days) unresolved acute diarrhea
  • Documented abnormal amniotic fluid volume on entry, such as polyhydramnios (amniotic fluid index greater than 25.0 cm), or oligohydramnios (amniotic fluid index less than 5.0 cm)
  • 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
  • Intent to breastfeed
  • Severe pre-existing skin disorder requiring systemic treatment (e.g., psoriasis, severe eczema)
  • 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 less than 8.0 mg/dL
    2. Absolute neutrophil count less than 1,000 cells/mm^3
    3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.5 times the upper limit of normal (ULN)
    4. Serum creatinine greater than 1.0 times the ULN
    5. Platelet count less than or equal to 50,000/uL
    6. Pancreatic amylase greater than 2.0 times the ULN, or total amylase greater than 2.0 times the ULN plus symptoms of pancreatitis or total amylase greater than 2.0 times the ULN plus lipase greater than 2.0 times the ULN
    7. Urine dipstick greater than 2+ protein
  • Evidence of pre-eclampsia (i.e., persistent hypertension greater than 90 mm Hg diastolic)
  • 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 28 Study Locations
Sponsors and Collaborators
Investigators
Study Chair: Esau Joao, M.D. Hospital 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: August 18, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Anti-HIV Agents
HIV Protease Inhibitors
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Lamivudine
Efavirenz
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Protease Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014