Reducing the Incidence of Nevirapine Resistance Mutations in Pregnant HIV Infected Women Who Receive Anti-HIV Drugs Prior to and After Giving Birth

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00109590
First received: April 29, 2005
Last updated: December 11, 2013
Last verified: December 2013
Results First Received: June 26, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics/Dynamics Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Didanosine, enteric-coated
Drug: Lopinavir/ritonavir
Drug: Nevirapine
Drug: Zidovudine

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Study participants were enrolled at seven IMPAACT affiliated sites in Thailand. Between June 9, 2006 and June 30, 2008, 175 participants enrolled in the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
The study recruited HIV infected pregnant women who were >= 18 years of age,>=28 to <38 weeks gestation, who did not plan to start antiretroviral treatment within eight weeks following delivery, not planning to breastfeed and had CD4+ count >250 cells/mm3. Women were randomized in approximately equal numbers to one of three treatment arms.

Reporting Groups
  Description
Arm A : LPV/r x 7d Nevirapine (NVP) 200 mg orally, single dose at onset of labor, Zidovudine (ZDV) 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 7 days postpartum, didanosine (ddI) 250 mg orally (if body weight <60 kg) or 400 mg orally daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 7 days postpartum, > Lopinavir/Ritonavir (LPV/r) 400/100mg orally twice daily at the onset of labor, during labor and for 7 days postpartum.
Arm B : no LPV/r Neviarpine (NVP) 200 mg orally, single dose at onset of labor, Zidovudine (ZDV) 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 30 days postpartum, didanosine (ddI) 250 mg orally (if body weight <60 kg) or 400 mg orally once daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 30 days postpartum.
Arm C: LPV/r x 30d Nevirapine (NVP) 200 mg orally, single dose at onset of labor, Zidovudine (ZDV) 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 30 days postpartum, didanosine (ddI) 250 mg orally (if body weight <60 kg) or 400 mg orally daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 30 days postpartum, Lopinavir/Ritonavir (LPV/r) 400/100mg orally twice daily at the onset of labor, during labor and for 30 days postpartum.

Participant Flow:   Overall Study
    Arm A : LPV/r x 7d     Arm B : no LPV/r     Arm C: LPV/r x 30d  
STARTED     57     58     60  
RECEIVED TREATMENT     56     56     57  
COMPLETED     55     56     56  
NOT COMPLETED     2     2     4  
Lost to Follow-up                 1                 0                 1  
Never Started Treatment                 1                 2                 3  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
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Reporting Groups
  Description
Arm A : LPV/r x 7d NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 7 days postpartum, ddI 250 mg orally (if body weight <60 kg) or 400 mg orally daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 7 days postpartum, LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 7 days postpartum.
Arm B : no LPV/r NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, every 3 hours during labor and twice daily for 30 days postpartum, ddI 250 mg orally (if body weight <60 kg) or 400 mg orally daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 30 days postpartum.
Arm C: LPV/r x 30d NVP 200 mg orally, single dose at onset of labor, ZDV 300 mg orally at onset of labor, evry 3 hours during labor and twice daily for 30 days postpartum, ddI 250 mg orally (if body weight <60 kg) or 400 mg orally daily (if body weight >= 60 kg) at the onset of labor, during labor, and for 30 days postpartum, LPV/r 400/100mg orally twice daily at the onset of labor, during labor and for 30 days postpartum.
Total Total of all reporting groups

Baseline Measures
    Arm A : LPV/r x 7d     Arm B : no LPV/r     Arm C: LPV/r x 30d     Total  
Number of Participants  
[units: participants]
  56     56     57     169  
Age  
[units: years]
Mean ± Standard Deviation
  27  ± 6     28  ± 5     27  ± 5     28  ± 5  
Age, Customized  
[units: participants]
       
18 to < 30years     34     35     38     107  
>=30 to < 45 years     21     21     19     61  
>= 45 years     1     0     0     1  
Gender  
[units: participants]
       
Female     56     56     57     169  
Male     0     0     0     0  
Gestational Age at Entry  
[units: weeks]
Median ( Full Range )
  32  
  ( 28 to 37 )  
  31  
  ( 27 to 38 )  
  31  
  ( 28 to 37 )  
  31  
  ( 27 to 38 )  
Duration of ZDV during pregnancy - At Entry  
[units: weeks]
Median ( Full Range )
  3  
  ( 0 to 9 )  
  2  
  ( 0 to 10 )  
  2  
  ( 0 to 27 )  
  3  
  ( 0 to 27 )  
Duration of ZDV during pregnancy - At Delivery  
[units: weeks]
Median ( Full Range )
  10  
  ( 2 to 16 )  
  11  
  ( 5 to 18 )  
  10  
  ( 0 to 31 )  
  10  
  ( 0 to 31 )  
CD4 cell count at entry  
[units: cells/uL]
Median ( Full Range )
  431  
  ( 262 to 1233 )  
  413  
  ( 251 to 1024 )  
  481  
  ( 262 to 1183 )  
  456  
  ( 251 to 1233 )  
CD4 cell count at delivery  
[units: cells/uL]
Median ( Full Range )
  484  
  ( 70 to 1001 )  
  517  
  ( 198 to 1150 )  
  566  
  ( 222 to 1182 )  
  513  
  ( 70 to 1182 )  
Plasma HIV RNA at entry  
[units: log10┬ácopies/mL]
Median ( Full Range )
  3.48  
  ( 2.60 to 4.98 )  
  3.52  
  ( 1.00 to 4.99 )  
  3.54  
  ( 2.60 to 5.05 )  
  3.49  
  ( 1.00 to 5.05 )  
Plasma HIV-RNA at delivery  
[units: log10┬ácopies/mL]
Median ( Full Range )
  3.63  
  ( 1.70 to 4.90 )  
  3.36  
  ( 1.70 to 4.83 )  
  3.48  
  ( 1.70 to 4.71 )  
  3.48  
  ( 1.70 to 4.90 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   The Proportion of Women Who Develop One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay in Plasma (Sampling Was Done at Days 10,21,30, and Weeks 5,6, and 8 Postpartum).   [ Time Frame: within 8 weeks postpartum. ]

2.  Primary:   The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations as Identified by Consensus Sequencing or Oligonucleotide Ligation Assay (OLA) in Plasma   [ Time Frame: at Day 10 or Week 6 postpartum. ]

3.  Primary:   Area Under the Curve Pharmacokinetic Outcome for LPV/r. (AUC ug*hr/mL)   [ Time Frame: Within 72 hours postpartum and during the first 30 days postpartum ]

4.  Primary:   Maximum Concentration Pharmacokinetic Outcome for LPV/r (Cmax ug/mL) .   [ Time Frame: Within 72 hours postpartum and during the first 30 days postpartum ]

5.  Primary:   Pre-dose Concentration Pharmacokinetic Outcome for LPV/r (Cpredose ug/mL).   [ Time Frame: Within 72 hours postpartum and during the first 30 days postpartum ]

6.  Primary:   Four (4) Hour Concentration Pharmacokinetic Outcome for LPV/r (C4hour ug/mL).   [ Time Frame: Within 72 hours postpartum and during the first 30 days postpartum ]

7.  Secondary:   The Proportion of Women in Each Randomized Arm Who Have One or More New NVP Resistance Mutations for the Subgroup of Women With Plasma HIV RNA >= 500 Copies/ml At Entry   [ Time Frame: at Day 10 or Week 6 postpartum. ]

8.  Secondary:   The Proportion of Women With Any New ZDV, ddI, or LPV/r Resistance Mutations.   [ Time Frame: At Week 5 postpartum (ZDV) and at the first timepoint with viral load >=500 copies/ml after treatment discontinuation (ddI and LPV/r). ]

9.  Secondary:   Number of Women With Grade >=3 Events After Start of Study Treatment   [ Time Frame: After start of study Treatment (postpartum) ]

10.  Secondary:   Proportion of Women With New NVP Resistance Mutation Within 8 Weeks Postpartum Who Had a NVP Resistance Mutation Detected at 72 Weeks Postpartum.   [ Time Frame: within 72 weeks postpartum ]

11.  Secondary:   Resistance Mutations in HIV Infected Infants   [ Time Frame: 24 weeks postpartum ]

12.  Secondary:   Median Viral Load (log10 Copies/ml) at 24 Weeks Postpartum in Women   [ Time Frame: at 24 weeks postpartum ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinialTrials.Gov@sdac.harvard.edu


Publications of Results:
Other Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00109590     History of Changes
Other Study ID Numbers: P1032, 10137, PACTG P1032
Study First Received: April 29, 2005
Results First Received: June 26, 2012
Last Updated: December 11, 2013
Health Authority: United States: Food and Drug Administration