Treatment Options for Protease Inhibitor-exposed Children
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. 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.
Timeline
- Start
- 2010-07
- Primary completion
- 2014-12
- Completion
- 2014-12
Outcome
Met primary endpoint
paper The risk difference for viral rebound was 0.107 (1-sided 95% CI, 0.028 to ∞) and for viral failure was -0.007 (1-sided 95% CI, -0.036 to ∞). PMID 26529159 ↗
paper We rejected the null hypothesis that efavirenz is inferior to ritonavir-boosted lopinavir (P < .001) for both end points. PMID 26529159 ↗
Publications
- Results 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.
- Murnane 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.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Abacavir | Other / unclassified | 8 mg/kg | — |
| Subject | Efavirenz | Other / unclassified | 200 mg | — |
| Subject | Efavirenz | Other / unclassified | 300 mg | — |
| Comparator | Lopinavir/ritonavir | Unknown | 230 mg/m2 | — |
| Comparator | Stavudine | Other / unclassified | 1 mg/kg | — |