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Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study.
Lancet Infect Dis. 2012 Jan; 12(1):27-35.LI

Abstract

BACKGROUND

Elvitegravir is a once daily inhibitor of HIV-1 integrase boosted by ritonavir. We aimed to compare the efficacy and safety of elvitegravir with raltegravir, another HIV-1 integrase inhibitor, in patients in whom previous antiretroviral treatment failed.

METHODS

We conducted a randomised, double-blind, double-dummy, phase 3 study at 234 sites in 13 countries. Eligible patients had plasma HIV RNA of 1000 copies per mL or greater, any CD4 cell count, and resistance to or 6 months' experience with at least two classes of antiretroviral drugs. They received an open-label background regimen of a fully active, ritonavir-boosted protease inhibitor and a second agent. We randomly allocated patients (1:1) by computer with a block size of four to receive either elvitegravir 150 mg once daily (n=361; 85 mg dose if given with atazanavir, or lopinavir with ritonavir) or raltegravir 400 mg twice daily (n=363). Placebo tablets were given to mask the difference in daily dosing. The primary endpoint was achievement and maintenance of virological response (HIV RNA <50 copies per mL) through week 48. Non-inferiority was prespecified with a margin of 10%. We did a modified intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00708162.

FINDINGS

Ten patients allocated elvitegravir and 12 assigned raltegravir were excluded from the analysis (either for protocol violations or because they did not receive treatment). 207 (59%) of 351 patients allocated elvitegravir achieved virological response compared with 203 (58%) of 351 assigned raltegravir (treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). Three patients allocated elvitegravir had serious adverse events related to study drugs compared with seven assigned raltegravir; two and eight patients died, respectively. More individuals assigned elvitegravir reported diarrhoea up to week 48 (p=0·023), and more patients assigned raltegravir had grade 3 or 4 rises in alanine aminotransferase (p=0·020) or aspartate aminotransferase (p=0·009).

INTERPRETATION

Elvitegravir used in combination with a ritonavir-boosted protease inhibitor in treatment-experienced patients has similar efficacy and safety to raltegravir. Since elvitegravir can be given once a day compared with twice a day for raltegravir, elvitegravir might improve patients' adherence.

FUNDING

Gilead Sciences.

Authors+Show Affiliations

Hôpital Saint Louis and University of Paris Diderot, Paris, France. jean-michel.molina@sls.aphp.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial, Phase III
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22015077

Citation

Molina, Jean-Michel, et al. "Efficacy and Safety of once Daily Elvitegravir Versus Twice Daily Raltegravir in Treatment-experienced Patients With HIV-1 Receiving a Ritonavir-boosted Protease Inhibitor: Randomised, Double-blind, Phase 3, Non-inferiority Study." The Lancet. Infectious Diseases, vol. 12, no. 1, 2012, pp. 27-35.
Molina JM, Lamarca A, Andrade-Villanueva J, et al. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012;12(1):27-35.
Molina, J. M., Lamarca, A., Andrade-Villanueva, J., Clotet, B., Clumeck, N., Liu, Y. P., Zhong, L., Margot, N., Cheng, A. K., & Chuck, S. L. (2012). Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. The Lancet. Infectious Diseases, 12(1), 27-35. https://doi.org/10.1016/S1473-3099(11)70249-3
Molina JM, et al. Efficacy and Safety of once Daily Elvitegravir Versus Twice Daily Raltegravir in Treatment-experienced Patients With HIV-1 Receiving a Ritonavir-boosted Protease Inhibitor: Randomised, Double-blind, Phase 3, Non-inferiority Study. Lancet Infect Dis. 2012;12(1):27-35. PubMed PMID: 22015077.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. AU - Molina,Jean-Michel, AU - Lamarca,Anthony, AU - Andrade-Villanueva,Jaime, AU - Clotet,Bonaventura, AU - Clumeck,Nathan, AU - Liu,Ya-Pei, AU - Zhong,Lijie, AU - Margot,Nicolas, AU - Cheng,Andrew K, AU - Chuck,Steven L, AU - ,, Y1 - 2011/10/18/ PY - 2011/10/22/entrez PY - 2011/10/22/pubmed PY - 2012/2/18/medline SP - 27 EP - 35 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 12 IS - 1 N2 - BACKGROUND: Elvitegravir is a once daily inhibitor of HIV-1 integrase boosted by ritonavir. We aimed to compare the efficacy and safety of elvitegravir with raltegravir, another HIV-1 integrase inhibitor, in patients in whom previous antiretroviral treatment failed. METHODS: We conducted a randomised, double-blind, double-dummy, phase 3 study at 234 sites in 13 countries. Eligible patients had plasma HIV RNA of 1000 copies per mL or greater, any CD4 cell count, and resistance to or 6 months' experience with at least two classes of antiretroviral drugs. They received an open-label background regimen of a fully active, ritonavir-boosted protease inhibitor and a second agent. We randomly allocated patients (1:1) by computer with a block size of four to receive either elvitegravir 150 mg once daily (n=361; 85 mg dose if given with atazanavir, or lopinavir with ritonavir) or raltegravir 400 mg twice daily (n=363). Placebo tablets were given to mask the difference in daily dosing. The primary endpoint was achievement and maintenance of virological response (HIV RNA <50 copies per mL) through week 48. Non-inferiority was prespecified with a margin of 10%. We did a modified intention-to-treat analysis. This study is registered with ClinicalTrials.gov, number NCT00708162. FINDINGS: Ten patients allocated elvitegravir and 12 assigned raltegravir were excluded from the analysis (either for protocol violations or because they did not receive treatment). 207 (59%) of 351 patients allocated elvitegravir achieved virological response compared with 203 (58%) of 351 assigned raltegravir (treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). Three patients allocated elvitegravir had serious adverse events related to study drugs compared with seven assigned raltegravir; two and eight patients died, respectively. More individuals assigned elvitegravir reported diarrhoea up to week 48 (p=0·023), and more patients assigned raltegravir had grade 3 or 4 rises in alanine aminotransferase (p=0·020) or aspartate aminotransferase (p=0·009). INTERPRETATION: Elvitegravir used in combination with a ritonavir-boosted protease inhibitor in treatment-experienced patients has similar efficacy and safety to raltegravir. Since elvitegravir can be given once a day compared with twice a day for raltegravir, elvitegravir might improve patients' adherence. FUNDING: Gilead Sciences. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/22015077/Efficacy_and_safety_of_once_daily_elvitegravir_versus_twice_daily_raltegravir_in_treatment_experienced_patients_with_HIV_1_receiving_a_ritonavir_boosted_protease_inhibitor:_randomised_double_blind_phase_3_non_inferiority_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(11)70249-3 DB - PRIME DP - Unbound Medicine ER -