Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya
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| ClinicalTrials.gov Identifier: NCT00427297 |
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Recruitment Status :
Terminated
(There is no longer equipoise. DSMB recommended termination.)
First Posted : January 29, 2007
Results First Posted : August 27, 2018
Last Update Posted : August 27, 2018
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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 or disease | Intervention/treatment | 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 3 |
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| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 34 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya (6-12 Month RCT) |
| Study Start Date : | September 2007 |
| Actual Primary Completion Date : | May 2009 |
| Actual Study Completion Date : | December 2009 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: NVP-containing
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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Active Comparator: NVP-sparing
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. |
- Incidence of Mortality [ Time Frame: 2 years ]Death during follow-up
- Immunologic Failure [ Time Frame: 2 years ]Immunologic treatment failure was defined as CD4% dropping below 15%, after a previous result greater than or equal to 15% (following along WHO Guidelines).
- Viral Failure [ Time Frame: 2 years ]Virologic treatment failure was defined as follow-up (at least 24 weeks after enrollment date) viral load > 400 copies.
- Incidence of Severe Adverse Events (Excluding Mortality) [ Time Frame: 2 years ]
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| Ages Eligible for Study: | 6 Months to 18 Months (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 6-18 months age
- HIV-1 DNA detection with confirmation (positive on two HIV-1 DNA filter paper tests)
- Mother exposed to NVP-containing PMTCT regimen during currently ended pregnancy and/or infant received NVP-containing PMTCT regimen
- Infant susceptible to NVP (i.e. no detectable NVP resistance on genotypic testing)
- Caregiver of infant plans to reside in Nairobi for at least 3 years
- Caregiver is able to provide sufficient location information
Exclusion Criteria:
- Infant has received any prior antiretroviral therapy (expect prophylaxis for PMTCT)
- Infant has evidence of active tuberculosis
- Mother currently receiving NVP-containing HAART and breastfeeding the infant
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00427297
| Kenya | |
| Kenyatta National Hospital, University of Nairobi | |
| Nairobi, Kenya | |
| 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: | Grace John-Stewart, Professor, Global Health, Medicine, Epidemiology, Pediatrics, University of Washington |
| ClinicalTrials.gov Identifier: | NCT00427297 |
| Other Study ID Numbers: |
STUDY00002049 2R01HD023412-16 ( U.S. NIH Grant/Contract ) 06-1886-D 02 |
| First Posted: | January 29, 2007 Key Record Dates |
| Results First Posted: | August 27, 2018 |
| Last Update Posted: | August 27, 2018 |
| Last Verified: | July 2018 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
| Product Manufactured in and Exported from the U.S.: | Yes |
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HIV-1 Pediatric nevirapine |
HAART Resistance Treatment Naive |
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HIV Infections Blood-Borne Infections Communicable Diseases Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Lopinavir Tenofovir |
Lamivudine Zidovudine Nevirapine Abacavir Stavudine Didanosine Efavirenz Dideoxynucleosides HIV Protease Inhibitors Viral Protease Inhibitors Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents |