A Phase 3 interventional study of Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) in HIV/AIDS and HIV Infections, sponsored by Columbia University. Completed at 1 site in South Africa. Open to participants aged 3 Years and older. Per ClinicalTrials.gov, last updated 2017-03-13.
Sponsored by Columbia University · Phase 3, Interventional, and Treatment
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.
4,258 studies on the registry are indexed under HIV Infections; 240 are open to participants now.
This study's enrollment of 300 is above the median of 83 across 3,251 interventional studies indexed under HIV Infections.
Browse HIV Infections studies →Columbia University is the lead sponsor of 1,103 studies on the registry; 193 are open to participants now.
Of its 172 completed or terminated interventional studies of FDA-regulated products, 142 (83%) have results posted.
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Exclusion criteria:
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.
Drug: Lopinavir/ritonavir (LPV/r)
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.
Drug: Efavirenz (EFV)
Children are assigned to remain on their current antiretroviral regimen, which includes D4T. D4T was given at 1 mg/kg twice daily
Drug: Stavudine (D4T)
Children stop taking D4T and switch to ABC. ABC was given at 8 mg/kg twice daily.
Drug: Abacavir (ABC)
Children are assigned to begin a EFV-based antiretroviral based regimen.
Children are assigned to stay on their current LPV/r-based antiretroviral regimen.
Children are assigned to stay on their current antiretroviral regimen which includes D4T.
Children stop taking D4T and switch to ABC.
Viral Rebound
Probability of viral rebound defined as \>=1 HIV RNA measurements \>50 copies/ml using survival analysis by 48 weeks post-randomization.
Time frame: 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.
Time frame: 48 weeks
CD4 Cell Percentage at 48 Weeks After Randomization
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
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
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).
Time frame: through 48 weeks post randomization
A total of 300 study participants were recruited between June 2010 and October 2012.
| Milestone | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| Started | 148 | 150 |
| Completed | 148 | 144 |
| Not completed | 0 | 6 |
| Withdrew: Transfer out | 0 | 6 |
Probability of viral rebound defined as \>=1 HIV RNA measurements \>50 copies/ml using survival analysis by 48 weeks post-randomization.
| probability of viral rebound | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| Viral Rebound | 0.284 (0.211 to 0.357) | 0.176 (0.115 to 0.238) |
Probability of viral failure defined as \>= 2 HIV RNA measurements \>1000 copies/ml using survival analysis by 48 weeks post-randomization.
| probability of viral failure | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| Viral Failure | 0.020 (0.002 to 0.043) | 0.027 (0.001 to 0.054) |
CD4 Cell Percentage at 48 Weeks After Randomization
| percentage of cells | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| CD4 Cell Percentage at 48 Weeks After Randomization | 34.7 (33.6 to 35.8) | 37.5 (36.3 to 38.8) |
Percentage of participants with elevated total cholesterol, elevated LDL, abnormal HDL, or abnormal triglycerides at 40 weeks after randomization
| percentage of participants | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| Elevated total cholesterol | 24.8 | 13.3 |
| Elevated LDL | 18.6 | 9.8 |
| Abnormal HDL | 4.8 | 4.2 |
| Abnormal triglycerides | 22.8 | 10.5 |
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).
| number of participants | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| Grade 0 | 139 | 120 |
| Grade 1 | 8 | 16 |
| Grade 2 | 0 | 10 |
| Grade 3 | 1 | 3 |
| Grade 4 | 0 | 1 |
Collected over Through 48 weeks after randomization. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Group 1: Lopinavir/Ritonavir (LPV/r) | — | 0/148 (0%) | 0/148 (0%) |
| Group 2: Efavirenz (EFV) | — | 2/150 (1.3%) | 0/150 (0%) |
| Event | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) |
|---|---|---|
| SeizureNervous system disorders | 0/148 | 2/150 |
| Age, Continuous(years) | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) | Total |
|---|---|---|---|
| Mean | 4.26 ± 1.0 | 4.28 ± 0.9 | 4.27 ± 0.9 |
| Sex: Female, Male(Participants) | Group 1: Lopinavir/Ritonavir (LPV/r) | Group 2: Efavirenz (EFV) | Total |
|---|---|---|---|
| Female | 80 | 78 | 158 |
| Male | 68 | 72 | 140 |
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