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Sponsors and Collaborators: |
University of Washington National Institute of Child Health and Human Development (NICHD) |
Information provided by: | University of Washington |
ClinicalTrials.gov Identifier: | NCT00427297 |
Globally, children who acquire HIV-1 increasingly do so in the context of maternal antiretroviral prophylaxis. It is important to determine whether maternal antiretroviral prophylaxis should alter infant treatment regimens. Nevirapine (NVP) is commonly used for PMTCT and is also a commonly used first-line drug for treatment of pediatric HIV-1. Approximately half of infants exposed to NVP have detectable NVP resistance early in infancy, with loss of detectable resistance over time. Thus, if an HIV-1 infected child was exposed to single-dose NVP prophylaxis, the question remains whether NVP or any NNRTI can be used effectively in therapeutic regimens. Alternative PI-based regimens are associated with heat-lability, poor palatability, cumulative toxicity, and fewer salvage options. This poses challenges for pediatric PI-based highly active antiretroviral therapy (HAART) in settings without refrigeration and limited antiretroviral repertoire. It is plausible that in older NVP-exposed infants (older than 6 months since exposure) who are genotypically NVP-susceptible, that nevirapine will be effective and useful.
We propose to study resistance in a pediatric HIV-1 clinical trial involving 100 children. Among children enrolled at between 6 and 18 months of age, we will provide real-time field-based genotypic NVP-resistance testing, and randomize 100 NVP-susceptible children to NVP-containing versus NVP-sparing HAART to compare therapeutic response, adverse events, and morbidity in the 2 arms during 2-year follow-up. Follow-up in these studies will be closely monitored by an external Data Safety and Monitoring Board (DSMB).
Condition | Intervention | Phase |
HIV Infections |
Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine) Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine) Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir) Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir) Drug: ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir) Drug: ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz) Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine) |
Phase III |
MedlinePlus related topics: | AIDS |
ChemIDplus related topics: | Zidovudine Abacavir Abacavir sulfate Lamivudine Didanosine Stavudine Efavirenz Ritonavir Nevirapine Lopinavir Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya |
Estimated Enrollment: | 100 |
Study Start Date: | September 2007 |
Estimated Study Completion Date: | December 2010 |
Estimated Primary Completion Date: | June 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
NVP-containing: Experimental
Infants randomized to this arm will receive nevirapine-containing HAART regimen
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Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
First line regimen
Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
First line regimen
Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
First line regimen
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NVP-sparing: Active Comparator
Infants randomized to this arm will receive nevirapine-sparing HAART
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Drug: AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
First line regimen
Drug: d4T/3TC/ABC (stavudine/lamivudine/abacavir)
First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.
Drug: ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
Second line regimen
Drug: ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)
Second line regimen - Among children randomized to NVP sparing HAART, who will be initiated on a regimen containing lopinavir/ritonavir, zidovudine and lamivudine will be substituted with abacavir and didanosine or tenofovir (TDF) and lopinavir/ ritonavir will be replaced with nevirapine or efavirenz (EFV) in case of treatment failure of the LPV/r containing regimen.
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Hypotheses
Specific Aims/Primary Objectives
Secondary Aim/Secondary Objective: To determine predictors of non-progression in these studies, including: age, time since nevirapine-exposure, adherence, HIV-1 specific immune responses, baseline HIV-1 RNA, CD4 percent, and immune activation.
Design: Randomized clinical trial in which infant 6-18 months of age will be randomized to nevirapine containing versus nevirapine sparing HAART regimen and followed for 24 months.
Population: HIV-1 infected infants (6-12 months) meeting eligibility will be enrolled. Infants who were exposed to nevirapine in-utero or following delivery, with no detectable resistance to nevirapine will be eligible for enrollment.
Sample size: 100 infants will be enrolled (50 infants in each arm).
Treatment: All infants will be treated with NVP containing or sparing HAART. The regimen will be prescribed according to WHO and Kenyan national guidelines on dosage and combination of antiretroviral drugs. The HAART regimen that will be used in this study are:
First line regimen:
For infants on NVP containing HAART
For infants on NVP sparing HAART
For children who have anaemia (Hb of <8g/dl), AZT will be substituted for d4T.
Second line regimen:
Ages Eligible for Study: | 6 Months to 18 Months |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Grace C John-Stewart, MD, PhD | 206-543-4278 | gjohn@u.washington.edu |
Kenya | |||||
Kenyatta National Hospital, University of Nairobi | Recruiting | ||||
Nairobi, Kenya | |||||
Contact: Agnes Langat, MMed (Paeds) 254-020-2731498 langat2004@yahoo.com | |||||
Principal Investigator: Dalton Wamalwa, MMed, MPH | |||||
Sub-Investigator: Dorothy Mbori-Ngacha, MMed, MPH | |||||
Sub-Investigator: Ruth Nduati, MMed, MPH | |||||
Sub-Investigator: Elizabeth Obimbo, MMed, MPH |
University of Washington |
National Institute of Child Health and Human Development (NICHD) |
Principal Investigator: | Grace C John-Stewart, MD, PhD | University of Washington |
Principal Investigator: | Dalton Wamalwa, MMed, MPH | Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi |
Responsible Party: | University of Washington ( Grace John-Stewart ) |
Study ID Numbers: | 06-1886-D 01, 2 RO1 HD023412-16 |
First Received: | January 22, 2007 |
Last Updated: | September 16, 2008 |
ClinicalTrials.gov Identifier: | NCT00427297 |
Health Authority: | United States: Institutional Review Board |
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