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Antiviral Responses to NNRTI-Based vs. PI-Based ARV Therapy in HIV Infected Infants Who Have or Have Not Received Single Dose NVP for Prevention of Mother-to-Child Transmission of HIV (P1060)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
National Institute of Allergy and Infectious Diseases (NIAID)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00307151
First received: March 24, 2006
Last updated: December 3, 2015
Last verified: December 2015
Results First Received: July 5, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Lamivudine
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 recruited at 10 study sites, 4 in South Africa and 1 each in Uganda, Zimbabwe, Zambia, Malawi, Tanzania and India between November 9, 2006 and March 19, 2010.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Infants and children 6 - 36 months of age (lower age limit changed to 2 months in Protocol Version 4.0) were stratified by age (2-<6 months, 6-<12 months and >=12 months) and randomly assigned to receive either AZT/3TC/NVP or AZT/3TC/LPV/r. One subject was randomized but never started study treatment.

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen

Participant Flow:   Overall Study
    Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r
STARTED   82   82   147   140 [1] 
COMPLETED   71 [2]   75 [2]   127 [3]   129 [3] 
NOT COMPLETED   11   7   20   11 
Death                4                3                10                3 
Severe debilitation, unable to continue                1                0                0                0 
Subject unable to get to clinic                1                0                6                2 
Withdrew consent                0                1                1                3 
Not willing to adhere to study reqs                2                0                2                2 
Clinic unable to contact subject                3                3                1                1 
[1] One participant never started treatment, were not followed and not included in analysis.
[2] Results are through date DSMB closed Cohort I to accrual (April 20, 2009)
[3] Results are through date DSMB recommended Cohort II results be unblinded (October 27, 2010)



  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
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen
Total Total of all reporting groups

Baseline Measures
   Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r   Total 
Overall Participants Analyzed 
[Units: Participants]
 82   82   147   140   451 
Age, Customized 
[Units: Participants]
         
<12 months   60   63   41   36   200 
>=12 months   22   19   106   104   251 
Gender 
[Units: Participants]
         
Female   46   41   78   72   237 
Male   36   41   69   68   214 
Race/Ethnicity, Customized 
[Units: Participants]
         
Black African   81   81   132   134   428 
Coloured   1   1   1   2   5 
Native of India   0   0   12   4   16 
Not available   0   0   2   0   2 
Region of Enrollment 
[Units: Participants]
         
Tanzania   2   0   8   7   17 
Zambia   2   4   14   18   38 
Uganda   1   4   20   20   45 
Malawi   2   0   16   20   38 
South Africa   71   65   41   36   213 
Zimbabwe   4   9   36   35   84 
India   0   0   12   4   16 
Ever breastfed 
[Units: Participants]
         
Yes   15   19   118   115   267 
No   67   63   29   25   184 
Documentation of SD NVP use at birth 
[Units: Participants]
         
Born before NVP available/mother known to have HIV   0   0   116   104   220 
Medical record review   62   63   10   12   147 
Verbal evidence only   20   19   19   22   80 
Found to have received SD NVP   0   0   2   2   4 
WHO Stage [1] 
[Units: Participants]
         
 7   18   29   25   79 
II   23   22   26   27   98 
III   39   38   80   77   234 
IV   13   4   12   11   40 
[1] World Health Organization (WHO) staging system for HIV infection and disease.
HIV-1 RNA 
[Units: Participants]
         
<100,000 copies/ml   6   5   20   27   58 
100,000 - < 750,000 copies/ml   27   34   70   53   184 
>=750,000 copies/ml   49   43   57   60   209 
CD4 Percent 
[Units: Participants]
         
<15 Percent   24   21   73   69   187 
15 Percent - < 25 Percent   37   37   60   54   188 
>= 25 Percent   21   24   13   17   75 
Missing   0   0   1   0   1 
NVP resistance 
[Units: Participants]
         
Yes   7   11   1   4   23 
No   68   62   110   91   331 
Not available   7   9   36   45   97 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percent of Participants With Treatment Failure, Defined as a Confirmed Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment   [ Time Frame: Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

2.  Secondary:   Time From Randomization to Treatment Failure, Defined as Virologic Failure or Permanent Discontinuation of the Randomized NNRTI or PI Component of Study Treatment   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

3.  Secondary:   Percent of Participants Experiencing Virologic Failure   [ Time Frame: Earlier of 24 weeks or date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

4.  Secondary:   Time From Randomization to Virologic Failure   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

5.  Secondary:   Time From Start of Study Treatment to First New Grade >=3 Lab Abnormality, Sign or Symptom Occurring on Study Treatment   [ Time Frame: On randomized NNRTI or PI component of study treatment and until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

6.  Secondary:   Number of Participants Developing New NRTI, NNRTI or PI-resistant Virus   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

7.  Secondary:   Change in CD4 Percent From Entry to Week 48   [ Time Frame: 48 weeks if before date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009; Coh II: October 27, 2010) ]

8.  Secondary:   Time From Randomization to HIV-related Disease Progression or Death   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]

9.  Secondary:   Time From Randomization to Death   [ Time Frame: Until date of DSMB decision to unblind Cohort results (Coh I: April 20, 2009 - median follow-up 48 weeks and range 0 - 125 weeks; Coh II: October 27, 2010 - median follow-up 72 weeks and range from 0 to 204 weeks) ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame From study enrollment until earlier of study completion or October 27, 2010 (primary completion date)
Additional Description Expedited adverse event (AE) reporting followed Intensive Division of AIDS (DAIDS) Reporting Level, which included AEs resulting in death, congenital anomalies, fetal losses, significant disabilities requiring hospitalization and >=grade 3 AEs defined by the "DAIDS Table for Grading the Severity of Adult and Pediatric AEs", V1.0, 12/2004.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Coh I: NVP Cohort I: Previously received single dose nevirapine (SD NVP). Randomly assigned to receive an NNRTI-based regimen.
Coh I: LPV/r Cohort I: Previously received SD NVP. Randomly assigned to receive a PI-based regimen.
Coh II: NVP Cohort II: Did not previously receive SD NVP. Randomly assigned to receive an NNRTI-based regimen.
Coh II: LPV/r Cohort II: Did not previously receive SD NVP. Randomly assigned to receive a PI-based regimen.

Other Adverse Events
    Coh I: NVP   Coh I: LPV/r   Coh II: NVP   Coh II: LPV/r
Total, other (not including serious) adverse events         
# participants affected / at risk   80/82 (97.56%)   81/82 (98.78%)   146/147 (99.32%)   140/140 (100.00%) 
Blood and lymphatic system disorders         
Anaemia † 1         
# participants affected / at risk   0/82 (0.00%)   1/82 (1.22%)   9/147 (6.12%)   1/140 (0.71%) 
Iron deficiency anaemia † 1         
# participants affected / at risk   1/82 (1.22%)   3/82 (3.66%)   13/147 (8.84%)   11/140 (7.86%) 
Lymphadenopathy † 1         
# participants affected / at risk   0/82 (0.00%)   2/82 (2.44%)   12/147 (8.16%)   9/140 (6.43%) 
Neutropenia † 1         
# participants affected / at risk   2/82 (2.44%)   2/82 (2.44%)   14/147 (9.52%)   12/140 (8.57%) 
Ear and labyrinth disorders         
Otorrhoea † 1         
# participants affected / at risk   2/82 (2.44%)   0/82 (0.00%)   11/147 (7.48%)   3/140 (2.14%) 
Eye disorders         
Conjunctivitis † 1         
# participants affected / at risk   5/82 (6.10%)   9/82 (10.98%)   36/147 (24.49%)   30/140 (21.43%) 
Eye discharge † 1         
# participants affected / at risk   1/82 (1.22%)   2/82 (2.44%)   13/147 (8.84%)   11/140 (7.86%) 
Ocular hyperaemia † 1         
# participants affected / at risk   1/82 (1.22%)   1/82 (1.22%)   12/147 (8.16%)   11/140 (7.86%) 
Gastrointestinal disorders         
Abdominal pain † 1         
# participants affected / at risk   1/82 (1.22%)   1/82 (1.22%)   13/147 (8.84%)   10/140 (7.14%) 
Diarrhoea † 1         
# participants affected / at risk   11/82 (13.41%)   15/82 (18.29%)   44/147 (29.93%)   40/140 (28.57%) 
Stomatitis † 1         
# participants affected / at risk   2/82 (2.44%)   2/82 (2.44%)   7/147 (4.76%)   11/140 (7.86%) 
Vomiting † 1         
# participants affected / at risk   7/82 (8.54%)   6/82 (7.32%)   42/147 (28.57%)   33/140 (23.57%) 
General disorders         
Pyrexia † 1         
# participants affected / at risk   11/82 (13.41%)   15/82 (18.29%)   62/147 (42.18%)   63/140 (45.00%) 
Infections and infestations         
Acarodermatitis † 1         
# participants affected / at risk   13/82 (15.85%)   13/82 (15.85%)   11/147 (7.48%)   9/140 (6.43%) 
Body tinea † 1         
# participants affected / at risk   2/82 (2.44%)   3/82 (3.66%)   13/147 (8.84%)   16/140 (11.43%) 
Bronchiolitis † 1         
# participants affected / at risk   4/82 (4.88%)   4/82 (4.88%)   10/147 (6.80%)   7/140 (5.00%) 
Bronchitis † 1         
# participants affected / at risk   9/82 (10.98%)   10/82 (12.20%)   7/147 (4.76%)   7/140 (5.00%) 
Bronchopneumonia † 1         
# participants affected / at risk   5/82 (6.10%)   1/82 (1.22%)   3/147 (2.04%)   5/140 (3.57%) 
Gastroenteritis † 1         
# participants affected / at risk   17/82 (20.73%)   19/82 (23.17%)   24/147 (16.33%)   16/140 (11.43%) 
Impetigo † 1         
# participants affected / at risk   11/82 (13.41%)   15/82 (18.29%)   11/147 (7.48%)   8/140 (5.71%) 
Malaria † 1         
# participants affected / at risk   4/82 (4.88%)   3/82 (3.66%)   30/147 (20.41%)   34/140 (24.29%) 
Oral candidiasis † 1         
# participants affected / at risk   20/82 (24.39%)   20/82 (24.39%)   31/147 (21.09%)   19/140 (13.57%) 
Oral herpes † 1         
# participants affected / at risk   2/82 (2.44%)   1/82 (1.22%)   12/147 (8.16%)   7/140 (5.00%) 
Otitis media † 1         
# participants affected / at risk   11/82 (13.41%)   14/82 (17.07%)   23/147 (15.65%)   17/140 (12.14%) 
Otitis media acute † 1         
# participants affected / at risk   13/82 (15.85%)   8/82 (9.76%)   25/147 (17.01%)   10/140 (7.14%) 
Persistent generalised lymphadenopathy † 1         
# participants affected / at risk   1/82 (1.22%)   3/82 (3.66%)   15/147 (10.20%)   16/140 (11.43%) 
Pharyngitis † 1         
# participants affected / at risk   10/82 (12.20%)   10/82 (12.20%)   19/147 (12.93%)   17/140 (12.14%) 
Plasmodium falciparum infection † 1         
# participants affected / at risk   2/82 (2.44%)   3/82 (3.66%)   31/147 (21.09%)   28/140 (20.00%) 
Pneumonia † 1         
# participants affected / at risk   15/82 (18.29%)   17/82 (20.73%)   36/147 (24.49%)   23/140 (16.43%) 
Pneumonia bacterial † 1         
# participants affected / at risk   2/82 (2.44%)   8/82 (9.76%)   20/147 (13.61%)   17/140 (12.14%) 
Pulmonary tuberculosis † 1         
# participants affected / at risk   10/82 (12.20%)   10/82 (12.20%)   10/147 (6.80%)   4/140 (2.86%) 
Purulent discharge † 1         
# participants affected / at risk   0/82 (0.00%)   1/82 (1.22%)   6/147 (4.08%)   7/140 (5.00%) 
Tinea capitis † 1         
# participants affected / at risk   6/82 (7.32%)   9/82 (10.98%)   21/147 (14.29%)   17/140 (12.14%) 
Tinea infection † 1         
# participants affected / at risk   10/82 (12.20%)   6/82 (7.32%)   19/147 (12.93%)   9/140 (6.43%) 
Tonsillitis † 1         
# participants affected / at risk   12/82 (14.63%)   12/82 (14.63%)   17/147 (11.56%)   20/140 (14.29%) 
Varicella † 1         
# participants affected / at risk   6/82 (7.32%)   5/82 (6.10%)   6/147 (4.08%)   7/140 (5.00%) 
Investigations         
Alanine aminotransferase increased † 1         
# participants affected / at risk   38/82 (46.34%)   26/82 (31.71%)   53/147 (36.05%)   33/140 (23.57%) 
Aspartate aminotransferase increased † 1         
# participants affected / at risk   45/82 (54.88%)   32/82 (39.02%)   40/147 (27.21%)   47/140 (33.57%) 
Blood cholesterol increased † 1         
# participants affected / at risk   2/82 (2.44%)   11/82 (13.41%)   7/147 (4.76%)   10/140 (7.14%) 
Blood triglycerides increased † 1         
# participants affected / at risk   1/82 (1.22%)   5/82 (6.10%)   8/147 (5.44%)   4/140 (2.86%) 
Haemoglobin decreased † 1         
# participants affected / at risk   57/82 (69.51%)   59/82 (71.95%)   121/147 (82.31%)   108/140 (77.14%) 
Neutrophil count decreased † 1         
# participants affected / at risk   52/82 (63.41%)   50/82 (60.98%)   90/147 (61.22%)   100/140 (71.43%) 
Platelet count decreased † 1         
# participants affected / at risk   2/82 (2.44%)   4/82 (4.88%)   13/147 (8.84%)   17/140 (12.14%) 
Weight decreased † 1         
# participants affected / at risk   2/82 (2.44%)   5/82 (6.10%)   18/147 (12.24%)   21/140 (15.00%) 
Metabolism and nutrition disorders         
Decreased appetite † 1         
# participants affected / at risk   2/82 (2.44%)   9/82 (10.98%)   29/147 (19.73%)   35/140 (25.00%) 
Failure to thrive † 1         
# participants affected / at risk   5/82 (6.10%)   9/82 (10.98%)   12/147 (8.16%)   6/140 (4.29%) 
Kwashiorkor † 1         
# participants affected / at risk   5/82 (6.10%)   0/82 (0.00%)   5/147 (3.40%)   4/140 (2.86%) 
Respiratory, thoracic and mediastinal disorders         
Cough † 1         
# participants affected / at risk   11/82 (13.41%)   14/82 (17.07%)   61/147 (41.50%)   60/140 (42.86%) 
Dyspnoea † 1         
# participants affected / at risk   4/82 (4.88%)   1/82 (1.22%)   13/147 (8.84%)   6/140 (4.29%) 
Pharyngeal erythema † 1         
# participants affected / at risk   1/82 (1.22%)   2/82 (2.44%)   5/147 (3.40%)   7/140 (5.00%) 
Pharyngeal inflammation † 1         
# participants affected / at risk   1/82 (1.22%)   3/82 (3.66%)   19/147 (12.93%)   18/140 (12.86%) 
Rhinorrhoea † 1         
# participants affected / at risk   4/82 (4.88%)   9/82 (10.98%)   50/147 (34.01%)   45/140 (32.14%) 
Wheezing † 1         
# participants affected / at risk   1/82 (1.22%)   1/82 (1.22%)   6/147 (4.08%)   8/140 (5.71%) 
Skin and subcutaneous tissue disorders         
Dermatitis allergic † 1         
# participants affected / at risk   2/82 (2.44%)   2/82 (2.44%)   12/147 (8.16%)   3/140 (2.14%) 
Eczema † 1         
# participants affected / at risk   7/82 (8.54%)   8/82 (9.76%)   15/147 (10.20%)   12/140 (8.57%) 
Papule † 1         
# participants affected / at risk   1/82 (1.22%)   3/82 (3.66%)   6/147 (4.08%)   18/140 (12.86%) 
Rash † 1         
# participants affected / at risk   17/82 (20.73%)   23/82 (28.05%)   68/147 (46.26%)   57/140 (40.71%) 
Rash generalised † 1         
# participants affected / at risk   8/82 (9.76%)   4/82 (4.88%)   16/147 (10.88%)   9/140 (6.43%) 
Rash papular † 1         
# participants affected / at risk   8/82 (9.76%)   7/82 (8.54%)   20/147 (13.61%)   33/140 (23.57%) 
Seborrhoeic dermatitis † 1         
# participants affected / at risk   10/82 (12.20%)   13/82 (15.85%)   7/147 (4.76%)   7/140 (5.00%) 
Skin reaction † 1         
# participants affected / at risk   4/82 (4.88%)   0/82 (0.00%)   8/147 (5.44%)   1/140 (0.71%) 
Skin ulcer † 1         
# participants affected / at risk   0/82 (0.00%)   3/82 (3.66%)   6/147 (4.08%)   8/140 (5.71%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0



  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
Accrual to Cohort I was terminated early by the Data Safety Monitoring Committee after enrollment of 164 of the planned 288 subjects.


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