HIV InfectionsPhase 3NCT00427297
Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya
A Phase 3 study testing AZT/3TC/NVP (zidovudine/lamivudine/nevirapine), d4T/3TC/NVP (stavudine/lamivudine/nevirapine) and AZT/3TC/ABC (zidovudine/lamivudine/abacavir) in people with HIV Infections, run by University of Washington at 1 site in Kenya.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 6 to 18 months
- Conditions the study is for
- HIV Infections
- What is being tested?
- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine), d4T/3TC/NVP (stavudine/lamivudine/nevirapine) and AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteKenya
- Study dates
- Sep 2007to Dec 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya (6-12 Month RCT)
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).
Read the detailed description
Hypotheses
- Infants older than 6 months who do not have detectable nevirapine resistance on genotypic testing will respond equivalently to a nevirapine-sparing or a nevirapine-containing HAART regimen, despite previous single-dose nevirapine exposure.
- Genotypic drug resistance levels may predict response to therapy and clinical progression.
Specific Aims/Primary Objectives
- To compare response to therapy (viral levels, CD4%, growth, and morbidity) in infants without detectable nevirapine-resistance on population-based sequencing who are randomized to nevirapine-containing versus nevirapine-sparing HAART.
- To develop methods to detect and quantify nevirapine resistance mutations present at low frequency in the virus population in order to examine the relationship between the copy number of such variants and virologic failure of infants treated with nevirapine-containing HAART.
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
- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
- d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
- ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
For infants on NVP sparing HAART
- AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
- d4T/3TC/ABC (stavudine/lamivudine/abacavir)
For children who have anaemia (Hb of <8g/dl), AZT will be substituted for d4T.
Second line regimen:
- ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir (kaletra))
- ABC / ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz) 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.
- Conditions
- HIV Infections
- Being tested
- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine), d4T/3TC/NVP (stavudine/lamivudine/nevirapine), AZT/3TC/ABC (zidovudine/lamivudine/abacavir), d4T/3TC/ABC (stavudine/lamivudine/abacavir), ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)
- Keywords
- HIV-1, Pediatric, nevirapine, HAART, Resistance, Treatment Naive
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)Drug
First line regimen
d4T/3TC/NVP (stavudine/lamivudine/nevirapine)Drug
First line regimen
AZT/3TC/ABC (zidovudine/lamivudine/abacavir)Drug
First line regimen
d4T/3TC/ABC (stavudine/lamivudine/abacavir)Drug
First line regimen For children who have anaemia(Hb of<8g/dl), AZT will be substituted for d4T.
ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)Drug
Second line regimen
ABC/ ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz)Drug
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.
ABC/3TC/NVP (abacavir/lamivudine/nevirapine)Drug
First line regimen
| Study group | Role | What they receive |
|---|---|---|
| NVP-containing | Experimental | Infants randomized to this arm will receive nevirapine-containing HAART regimen Receives: Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine); Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine); Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine) |
| NVP-sparing | Active comparator | Infants randomized to this arm will receive nevirapine-sparing HAART Receives: 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) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Mortality
Death during follow-up
Measured: 2 years
Immunologic Failure
Immunologic treatment failure was defined as CD4% dropping below 15%, after a previous result greater than or equal to 15% (following along WHO Guidelines).
Measured: 2 years
Viral Failure
Virologic treatment failure was defined as follow-up (at least 24 weeks after enrollment date) viral load > 400 copies.
Measured: 2 years
Secondary outcomes (1)
Incidence of Severe Adverse Events (Excluding Mortality)
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2007 (estimated)
- Study startSep 2007
- Primary completionMay 2009
- Study completionDec 2009
Why it stopped: There is no longer equipoise. DSMB recommended termination.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Grace John-Stewart, University of Washington
- Investigators
- Grace C John-Stewart, MD, PhD, Principal investigator, University of WashingtonDalton Wamalwa, MMed, MPH, Principal investigator, Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00427297
- Sponsor's protocol ID
- STUDY00002049
- Other IDs
- 2R01HD023412-16, 06-1886-D 02
- Status last verified
- Jul 2018
- First submitted
- 22 Jan 2007
- Last updated
- 27 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimizing Pediatric HIV-1 Treatment in Infants With Prophylactic Exposure to Nevirapine, Nairobi, Kenya (6-12 Month RCT)
- ClinicalTrials.gov ID
- NCT00427297
- Acronym / sponsor ID
- STUDY00002049
- Conditions
- HIV Infections
- Keywords
- HIV-1, Pediatric, nevirapine, HAART, Resistance, Treatment Naive
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: There is no longer equipoise. DSMB recommended termination.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Sep 2007
- Primary completion
- May 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 29 Jan 2007 (estimated)
- Results
- Posted 27 Aug 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
Hypotheses
- Infants older than 6 months who do not have detectable nevirapine resistance on genotypic testing will respond equivalently to a nevirapine-sparing or a nevirapine-containing HAART regimen, despite previous single-dose nevirapine exposure.
- Genotypic drug resistance levels may predict response to therapy and clinical progression.
Specific Aims/Primary Objectives
- To compare response to therapy (viral levels, CD4%, growth, and morbidity) in infants without detectable nevirapine-resistance on population-based sequencing who are randomized to nevirapine-containing versus nevirapine-sparing HAART.
- To develop methods to detect and quantify nevirapine resistance mutations present at low frequency in the virus population in order to examine the relationship between the copy number of such variants and virologic failure of infants treated with nevirapine-containing HAART.
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
- AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)
- d4T/3TC/NVP (stavudine/lamivudine/nevirapine)
- ABC/3TC/NVP (abacavir/lamivudine/nevirapine)
For infants on NVP sparing HAART
- AZT/3TC/ABC (zidovudine/lamivudine/abacavir)
- d4T/3TC/ABC (stavudine/lamivudine/abacavir)
For children who have anaemia (Hb of <8g/dl), AZT will be substituted for d4T.
Second line regimen:
- ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir (kaletra))
- ABC / ddI or TDF / NVP or EFV (abacavir / didanosine or tenofovir / nevirapine or efavirenz) 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NVP-containing | Experimental | Drug: AZT/3TC/NVP (zidovudine/lamivudine/nevirapine), Drug: d4T/3TC/NVP (stavudine/lamivudine/nevirapine), Drug: ABC/3TC/NVP (abacavir/lamivudine/nevirapine)Infants randomized to this arm will receive nevirapine-containing HAART regimen |
| NVP-sparing | Active comparator | 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)Infants randomized to this arm will receive nevirapine-sparing HAART |
Who may qualify
- Ages
- 6 to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (3 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZT/3TC/NVP (zidovudine/lamivudine/nevirapine)First line regimen | Drug | NVP-containing |
| d4T/3TC/NVP (stavudine/lamivudine/nevirapine)First line regimen | Drug | NVP-containing |
| AZT/3TC/ABC (zidovudine/lamivudine/abacavir)First line regimen | Drug | NVP-sparing |
| 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 | NVP-sparing |
| ddI/ABC/LPV/r (didanosine/abacavir/lopinavir-ritonavir)Second line regimen | Drug | NVP-sparing |
| 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. | Drug | NVP-sparing |
| ABC/3TC/NVP (abacavir/lamivudine/nevirapine)First line regimen | Drug | NVP-containing |
Primary outcome
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.
1 secondary outcome
Incidence of Severe Adverse Events (Excluding Mortality)
Time frame: 2 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Grace C John-Stewart, MD, PhD principal investigator
University of Washington
Dalton Wamalwa, MMed, MPH principal investigator
Department of Paediatrics and Child Health, Kenyatta National Hospital, University of Nairobi
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing AZT/3TC/NVP (zidovudine/lamivudine/nevirapine), d4T/3TC/NVP (stavudine/lamivudine/nevirapine) and AZT/3TC/ABC (zidovudine/lamivudine/abacavir) in people with HIV Infections, run by University of Washington at 1 site in Kenya.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Aug 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Mortality (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Aug 2018.