Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Trial of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV Transmission

This study has been completed.
Sponsor:
Collaborator:
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00099359
First received: December 10, 2004
Last updated: October 26, 2012
Last verified: February 2011
Results First Received: April 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: Disease Transmission, Vertical
Vertical Human Immunodeficiency Virus Transmission
HIV Infections
Interventions: Drug: Zidovudine
Drug: Nevirapine (NVP)
Drug: Epivir (3TC)
Drug: Nelfinavir (NFV)

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The first subject was enrolled on 02/27/2004 and the study ended 02/28/2011. A total of 17 sites in Brazil, South Africa, Argentina and the U.S. participated in the study.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Arm A (ZDV Only) Standard of care ( Zidovudine only). 12 mg PO BID if BW>2000 grams ; 8 mg PO BID if BW</= 2000 grams
ARM B (ZDV + NVP)

Standard of care (Zidovudine) plus Nevirapine (NVP)

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams

ARM C (ZDV + 3TC + NFV)

Standard of Care (Zidovudine) plus 2 weeks of Epivir (3TC) and Nelfinavir (NFV) 3TC, given for 2 weeks: 6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 – 3000 grams 100 mg PO BID if BW < 2000 grams


Participant Flow:   Overall Study
    Arm A (ZDV Only)   ARM B (ZDV + NVP)   ARM C (ZDV + 3TC + NFV)
STARTED   581   580   574 
COMPLETED   527   515   506 
NOT COMPLETED   54   65   68 
Death                11                15                17 
Withdrawal by Subject                19                19                23 
Lost to Follow-up                15                24                24 
moved out of area                9                7                4 



  Baseline Characteristics
  Hide Baseline Characteristics

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.
No text entered.

Reporting Groups
  Description
Arm A (ZDV Only) Standard of care ( Zidovudine only). 12 mg PO BID if BW>2000 grams ; 8 mg PO BID if BW</= 2000 grams
ARM B (ZDV + NVP)

Standard of care (Zidovudine) plus Nevirapine (NVP)

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams

ARM C (ZDV + 3TC + NFV)

Standard of Care (Zidovudine) plus 2 weeks of Epivir (3TC) and Nelfinavir (NFV) 3TC, given for 2 weeks: 6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 – 3000 grams 100 mg PO BID if BW < 2000 grams

Total Total of all reporting groups

Baseline Measures
   Arm A (ZDV Only)   ARM B (ZDV + NVP)   ARM C (ZDV + 3TC + NFV)   Total 
Overall Participants Analyzed 
[Units: Participants]
 581   580   574   1735 
Age 
[Units: Weeks]
Mean (Standard Deviation)
       
Gestational Age in Weeks   39  (1.7)   39  (1.5)   39  (1.7)   39  (1.7) 
Gender 
[Units: Participants]
       
Female   298   303   281   882 
Male   283   277   293   853 
Region of Enrollment 
[Units: Participants]
       
United States   4   4   4   12 
Puerto Rico   0   1   1   2 
Argentina   10   6   11   27 
Brazil   409   408   402   1219 
South Africa   158   161   156   475 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Infant HIV Infection Status   [ Time Frame: 3 months ]

2.  Primary:   Participants With Serious Adverse Events   [ Time Frame: through age 6 months. ]

3.  Secondary:   Infant HIV-1 Infection Status   [ Time Frame: birth ]

4.  Secondary:   Participant Deaths   [ Time Frame: through age 6 months ]

5.  Secondary:   3TC and NFV Pharmacokinetics   [ Time Frame: through age 14 days ]

6.  Secondary:   Risk Factors for Perinatal HIV-1 Transmission   [ Time Frame: through age 3 months ]
  Hide Outcome Measure 6

Measure Type Secondary
Measure Title Risk Factors for Perinatal HIV-1 Transmission
Measure Description Risk factors to be assessed include maternal HIV-1 RNA levels at delivery, maternal syphilis and other infections, obstetrical factors such as duration of membrane rupture, and adherence to neonatal medication.
Time Frame through age 3 months  
Safety Issue No  

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.
All available demographic and clinical variables were tested for association with transmission rate. All variables that were significant at p ≤ 0.20 were included in the multivariable regression model. Variables that were not significant were then removed from the model. The backward elimination method was used to select the final model.

Reporting Groups
  Description
Infected Infants infected after birth
Uninfected Infants uninfected after birth

Measured Values
   Infected   Uninfected 
Participants Analyzed 
[Units: Participants]
 47   1544 
Risk Factors for Perinatal HIV-1 Transmission 
[Units: Participants]
   
Treatment Arm C (ZDV+3TC/NFV)   12   516 
Treatment Arm B (ZDV+NFV)   11   523 
Treatment Arm A (ZDV only)   24   505 
Illegal Substance Abuse during pregnancy   7   130 


Statistical Analysis 1 for Risk Factors for Perinatal HIV-1 Transmission
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.05
Odds Ratio (OR) [4] 0.50
95% Confidence Interval 0.24 to 1.01
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted Odds ratio for treatment arm C (ZDV+3TC/NFV) association with Intrapartum Infection Status with Treatment Arm A (ZDV only) as reference group
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 2 for Risk Factors for Perinatal HIV-1 Transmission
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.01
Odds Ratio (OR) [4] 0.39
95% Confidence Interval 0.19 to 0.82
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted odds ratio for association of treatment arm B (ZDV+NVP) with intrapartum infection status with Treatment Arm A (ZDV only) as reference.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 3 for Risk Factors for Perinatal HIV-1 Transmission
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] 0.03
Odds Ratio (OR) [4] 2.51
95% Confidence Interval 1.08 to 5.86
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  Adjusted odds ratio for association of illegal substance use during pregnancy and intrapartum HIV infection status with "NO" being reference group.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  No text entered.

Statistical Analysis 4 for Risk Factors for Perinatal HIV-1 Transmission
Groups [1] All groups
Method [2] Regression, Logistic
P Value [3] <0.0001
Odds Ratio (OR) [4] 2.28
95% Confidence Interval 1.56 to 3.35
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Adjusted odds ratio for the association of continuous log10 viral load with intrapartum infection status
[4] Other relevant estimation information:
  No text entered.



7.  Secondary:   NVP Pharmacokinetics   [ Time Frame: 14 days ]

8.  Secondary:   Clinical Covariates of HIV-1 Infection   [ Time Frame: through age 3 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information