HIV/AIDSPhase 3NEVEREST-IIINCT01146873
Treatment Options for Protease Inhibitor-exposed Children
A Phase 3 study testing Efavirenz (EFV), Lopinavir/ritonavir (LPV/r) and Stavudine (D4T) in people with HIV/AIDS and HIV Infections, run by Columbia University at 1 site in South Africa.
Trial summary
The investigators hypothesize that switching to a regimen based on efavirenz will be as effective and safe as remaining on a regimen based on Lopinavir/ritonavir for HIV-infected children. Read more about this study
- Who is it for?
- Ages 3 years and older
- Conditions the study is for
- HIV/AIDS, HIV Infections
- What is being tested?
- Efavirenz (EFV), Lopinavir/ritonavir (LPV/r) and Stavudine (D4T)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 300 participants
- Where
- 1 siteSouth Africa
- Study dates
- Jul 2010to Dec 2014
- 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 3 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- HIV-infected child 3 to 5 years of age at time of screening for this trial if enrolled from outside or any age if enrolled from control arm of Neverest II.
- Reliable history or documented exposure to NVP used as part of PMTCT
- Initiated antiretroviral therapy with LPV/r at age less than 36 months
- Receiving LPV/r-based ART for at least 12 months
- At least one viral load measurement less than 50 copies/ml conducted as part of screening for the study
- ALT measurement grade I or less (DAIDS Toxicity Tables 2004) (Appendix A). These may be repeated until ALTs normalize if necessary.
Who cannot join
- Prior treatment with any NNRTI drug as part of a therapeutic regimen
- Substitution of other NRTI drugs (instead of 3TC and D4T which are the standard first line regimen) will be allowed.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Rahima Moosa Mother and Child Hospital
Johannesburg, Gauteng
About this study
The investigators hypothesize that switching to a regimen based on efavirenz will be as effective and safe as remaining on a regimen based on Lopinavir/ritonavir for HIV-infected children.
The investigators propose an unblinded randomized clinical trial to evaluate a simplification, protease-inhibitor (PI)-sparing treatment strategy among nevirapine (NVP)-exposed HIV-infected children treated initially with lopinavir/ritonavir (LPV/r). HIV-infected children aged 3-5 years, who have a history of exposure to NVP as part of prevention of mother-to-child HIV transmission (PMTCT), initiated LPV/r-based therapy in the first 36 months of life or who were enrolled on the control arm of Neverest 2 and who are virally suppressed with a viral load < 50 copies/ml will be included. These children will be randomized to either substitute efavirenz (EFV) for LPV/r or to continue on their LPV/r-based regimen. Eight weeks prior to the primary randomization, eligible children will also be randomized to either remain on stavudine (D4T) or switch to abacavir (ABC). Children will be followed with regular viral load and other clinical tests for 48 weeks after the primary randomization. Children in the experimental arm who have breakthrough viremia (-defined as two subsequent viral loads > 1000 copies/ml) on the EFV-based regimen will reinitiate the LPV/r regimen. The primary objective is to test whether the durability of viral suppression is equivalent when children are switched to EFV-based therapy. The primary study endpoint is failure to have HIV RNA < 50 copies/ml and/or confirmed viremia >1000 copies/ml. Secondary aims include comparison of immune preservation, toxicities, selection of resistance mutations, and adherence across the two arms. Antiretroviral drug concentrations and adherence will be investigated as possible explanations for the success and/or failure of this simplification regimen. The overall goal of the study is to contribute to the evidence base to allow expansion of treatment options for HIV-infected children in low resource settings.
- Conditions
- HIV/AIDS, HIV Infections
- Being tested
- Efavirenz (EFV), Lopinavir/ritonavir (LPV/r), Stavudine (D4T), Abacavir (ABC)
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Efavirenz (EFV)Drug
Children are assigned to begin a EFV-based antiretroviral based regimen.
Lopinavir/ritonavir (LPV/r)Drug
Children are assigned to stay on their current LPV/r-based antiretroviral regimen.
Stavudine (D4T)Drug
Children are assigned to stay on their current antiretroviral regimen which includes D4T.
Abacavir (ABC)Drug
Children stop taking D4T and switch to ABC.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Lopinavir/ritonavir (LPV/r) | Active comparator | Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m^2 or 2 tablets twice per day if body surface area was 0.9m^2 or higher. Receives: Drug: Lopinavir/ritonavir (LPV/r) |
| Group 2: Efavirenz (EFV) | Experimental | Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water. Receives: Drug: Efavirenz (EFV) |
| Group D: Stavudine (D4T) | Active comparator | Children are assigned to remain on their current antiretroviral regimen, which includes D4T. D4T was given at 1 mg/kg twice daily Receives: Drug: Stavudine (D4T) |
| Group A: Abacavir (ABC) | Experimental | Children stop taking D4T and switch to ABC. ABC was given at 8 mg/kg twice daily. Receives: Drug: Abacavir (ABC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Viral Rebound
Probability of viral rebound defined as >=1 HIV RNA measurements >50 copies/ml using survival analysis by 48 weeks post-randomization.
Measured: 48 weeks
Viral Failure
Probability of viral failure defined as >= 2 HIV RNA measurements >1000 copies/ml using survival analysis by 48 weeks post-randomization.
Measured: 48 weeks
Secondary outcomes (3)
CD4 Cell Percentage at 48 Weeks After Randomization
CD4 Cell Percentage at 48 Weeks After Randomization
Measured: 48 weeks
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization
Percentage of participants with elevated total cholesterol, elevated LDL, abnormal HDL, or abnormal triglycerides at 40 weeks after randomization
Measured: 40 weeks
Highest Grade ALT After Randomization
Highest grade ALT after randomization. Grading was determined based on the Division of AIDS (2004) Toxicity Tables to grade adverse reactions. Grading scale: 0 (none), 1 (mild), 2 (moderate), 3 (severe), 4 (potentially life-threatening).
Measured: through 48 weeks post randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2010 (estimated)
- Study startJul 2010
- Primary completionDec 2014
- Study completionDec 2014
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe 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
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Witwatersrand, South Africa, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Louise Kuhn, Columbia University
- Investigators
- Louise Kuhn, PhD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01146873
- Sponsor's protocol ID
- AAAE1145
- Other IDs
- R01HD061255
- Acronym
- NEVEREST-III
- Status last verified
- Jan 2017
- First submitted
- 8 Jun 2010
- Last updated
- 13 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, Patel F, Hunt G, Tsai WY, Kuhn L. Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial. JAMA. 2015 Nov 3;314(17):1808-17. doi: 10.1001/jama.2015.13631.
PubMed 26529159Murnane PM, Strehlau R, Shiau S, Patel F, Mbete N, Hunt G, Abrams EJ, Coovadia A, Kuhn L. Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial. Clin Infect Dis. 2017 Aug 1;65(3):477-485. doi: 10.1093/cid/cix335.
PubMed 28419200
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment Options for Protease Inhibitor-exposed Children
- ClinicalTrials.gov ID
- NCT01146873
- Acronym / sponsor ID
- NEVEREST-III / AAAE1145
- Conditions
- HIV/AIDS, HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- University of Witwatersrand, South Africa, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- Jul 2010
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 22 Jun 2010 (estimated)
- Results
- Posted 4 May 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that switching to a regimen based on efavirenz will be as effective and safe as remaining on a regimen based on Lopinavir/ritonavir for HIV-infected children.
The investigators propose an unblinded randomized clinical trial to evaluate a simplification, protease-inhibitor (PI)-sparing treatment strategy among nevirapine (NVP)-exposed HIV-infected children treated initially with lopinavir/ritonavir (LPV/r). HIV-infected children aged 3-5 years, who have a history of exposure to NVP as part of prevention of mother-to-child HIV transmission (PMTCT), initiated LPV/r-based therapy in the first 36 months of life or who were enrolled on the control arm of Neverest 2 and who are virally suppressed with a viral load < 50 copies/ml will be included. These children will be randomized to either substitute efavirenz (EFV) for LPV/r or to continue on their LPV/r-based regimen. Eight weeks prior to the primary randomization, eligible children will also be randomized to either remain on stavudine (D4T) or switch to abacavir (ABC). Children will be followed with regular viral load and other clinical tests for 48 weeks after the primary randomization. Children in the experimental arm who have breakthrough viremia (-defined as two subsequent viral loads > 1000 copies/ml) on the EFV-based regimen will reinitiate the LPV/r regimen. The primary objective is to test whether the durability of viral suppression is equivalent when children are switched to EFV-based therapy. The primary study endpoint is failure to have HIV RNA < 50 copies/ml and/or confirmed viremia >1000 copies/ml. Secondary aims include comparison of immune preservation, toxicities, selection of resistance mutations, and adherence across the two arms. Antiretroviral drug concentrations and adherence will be investigated as possible explanations for the success and/or failure of this simplification regimen. The overall goal of the study is to contribute to the evidence base to allow expansion of treatment options for HIV-infected children in low resource settings.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: Lopinavir/ritonavir (LPV/r) | Active comparator | Drug: Lopinavir/ritonavir (LPV/r)Participants are assigned to remain on their current LPV/r-based antiretroviral regimen. Ritonavir-boosted lopinavir syrup was given twice per day at 230 mg/m^2 per dose. Children able to swallow tablets were given 1 tablet twice per day (200 mg lopinavir/50 mg ritonavir) if body surface area was less than 0.9m^2 or 2 tablets twice per day if body surface area was 0.9m^2 or higher. |
| Group 2: Efavirenz (EFV) | Experimental | Drug: Efavirenz (EFV)Participants are assigned to switch to an EFV-based antiretroviral regimen. Efavirenz was prescribed once daily in the evening at 200 mg for weights of 10 kg to 13.9 kg (22-30 lb) and 300mg for weights of 14 kg to 24.9 kg (31-55 lb). Efavirenz was available in 50-mg and 200-mg capsules. If children were unable to swallow capsules, caregivers were shown how to open the capsules and dissolve the contents in water. |
| Group D: Stavudine (D4T) | Active comparator | Drug: Stavudine (D4T)Children are assigned to remain on their current antiretroviral regimen, which includes D4T. D4T was given at 1 mg/kg twice daily |
| Group A: Abacavir (ABC) | Experimental | Drug: Abacavir (ABC)Children stop taking D4T and switch to ABC. ABC was given at 8 mg/kg twice daily. |
Who may qualify
- Ages
- 3 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- HIV-infected child 3 to 5 years of age at time of screening for this trial if enrolled from outside or any age if enrolled from control arm of Neverest II.
- Reliable history or documented exposure to NVP used as part of PMTCT
- Initiated antiretroviral therapy with LPV/r at age less than 36 months
- Receiving LPV/r-based ART for at least 12 months
- At least one viral load measurement less than 50 copies/ml conducted as part of screening for the study
Key exclusion criteria (2 listed)
- Prior treatment with any NNRTI drug as part of a therapeutic regimen
- Substitution of other NRTI drugs (instead of 3TC and D4T which are the standard first line regimen) will be allowed.
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 |
|---|---|---|
| Efavirenz (EFV)Children are assigned to begin a EFV-based antiretroviral based regimen. | Drug | Group 2: Efavirenz (EFV) |
| Lopinavir/ritonavir (LPV/r)Children are assigned to stay on their current LPV/r-based antiretroviral regimen. | Drug | Group 1: Lopinavir/ritonavir (LPV/r) |
| Stavudine (D4T)Children are assigned to stay on their current antiretroviral regimen which includes D4T. | Drug | Group D: Stavudine (D4T) |
| Abacavir (ABC)Children stop taking D4T and switch to ABC. | Drug | Group A: Abacavir (ABC) |
Primary outcome
Viral Rebound
Time frame: 48 weeks
Probability of viral rebound defined as >=1 HIV RNA measurements >50 copies/ml using survival analysis by 48 weeks post-randomization.
Viral Failure
Time frame: 48 weeks
Probability of viral failure defined as >= 2 HIV RNA measurements >1000 copies/ml using survival analysis by 48 weeks post-randomization.
3 secondary outcomes
CD4 Cell Percentage at 48 Weeks After Randomization
Time frame: 48 weeks
Percentage of Participants With Elevated Total Cholesterol, Elevated LDL, Abnormal HDL, or Abnormal Triglycerides at 40 Weeks After Randomization
Time frame: 40 weeks
Highest Grade ALT After Randomization
Time frame: through 48 weeks post randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26529159Coovadia A, Abrams EJ, Strehlau R, Shiau S, Pinillos F, Martens L, Patel F, Hunt G, Tsai WY, Kuhn L. Efavirenz-Based Antiretroviral Therapy Among Nevirapine-Exposed HIV-Infected Children in South Africa: A Randomized Clinical Trial. JAMA. 2015 Nov 3;314(17):1808-17. doi: 10.1001/jama.2015.13631.
- Derived from this study: PubMed 28419200Murnane PM, Strehlau R, Shiau S, Patel F, Mbete N, Hunt G, Abrams EJ, Coovadia A, Kuhn L. Switching to Efavirenz Versus Remaining on Ritonavir-boosted Lopinavir in Human Immunodeficiency Virus-infected Children Exposed to Nevirapine: Long-term Outcomes of a Randomized Trial. Clin Infect Dis. 2017 Aug 1;65(3):477-485. doi: 10.1093/cid/cix335.
Related trials for HIV/AIDS
Enrolling by invitation
ORCHID: An Online Intervention for Persons With HIV (Miami)
HIV/AIDS, HPV Infection
Recruiting
Enhancing the Organizational Social Context to Improve Viral Suppression and Retention in HIV Care
HIV/AIDS
RecruitingPhase 1/2
SV2A & TSPO PET Imaging Measures to Reveal Mechanisms of HIV Neuropathogenesis During Antiretroviral Therapy
HIV Associated Neurocognitive Disorder, HIV Dementia
Recruiting
Peer-led Dynamic Choice HIV Prevention for Women: The Peer-led DCP Randomized Trial
HIV/AIDS, HIV/AIDS Prevention
Active, not recruitingPhase 2
Therapy Adapted for High Risk and Low Risk HIV-Associated Anal Cancer
AIDS-Related Anal Carcinoma, Anal Margin Squamous Cell Carcinoma
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.
Louise Kuhn, PhD principal investigator
Columbia University
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 Efavirenz (EFV), Lopinavir/ritonavir (LPV/r) and Stavudine (D4T) in people with HIV/AIDS and HIV Infections, run by Columbia University at 1 site in South Africa.
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 2 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: finished, as of the sponsor's last update on 13 Mar 2017. 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 South Africa. 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 4 May 2016). 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?
Viral Rebound (time frame: 48 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01146873, which also lists 2 linked publications.
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 13 Mar 2017; AzTrials last refreshed its copy on 7 Nov 2026.