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;   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
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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
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
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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.
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 ]

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.  


  Serious Adverse Events


  Other Adverse Events
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Time Frame through 6 months
Additional Description AE data collected from study entry to off study period

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
ARM A (ZDV Alone)

ZDV, given for 6 weeks:

12 mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams

ARM B (ZDV + NVP)

ZDV, given for 6 weeks:

12 mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams

AND 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)

ZDV, given for 6 weeks:

12 mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams AND 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


Other Adverse Events
    ARM A (ZDV Alone)   ARM B (ZDV + NVP)   ARM C (ZDV + 3TC/NFV)
Total, Other (not including serious) Adverse Events       
# participants affected / at risk   492/581 (84.68%)   482/580 (83.10%)   480/574 (83.62%) 
Blood and lymphatic system disorders       
Anaemia NOS † 1       
# participants affected / at risk   286/581 (49.23%)   270/580 (46.55%)   287/574 (50.00%) 
# events   451   402   456 
neutropenia † 1       
# participants affected / at risk   225/581 (38.73%)   119/580 (20.52%)   244/574 (42.51%) 
# events   294   261   334 
Infections and infestations       
oral candidiasis † 1       
# participants affected / at risk   162/581 (27.88%)   170/580 (29.31%)   156/574 (27.18%) 
# events   188   194   177 
Investigations       
Aspartate Aminotransferase Increased † 1       
# participants affected / at risk   335/581 (57.66%)   317/580 (54.66%)   325/574 (56.62%) 
# events   439   429   418 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 6.0



  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