Activity of Elvitegravir, a Once-Daily Integrase Inhibitor, against Resistant HIV Type 1: Results of a Phase 2, Randomized, Controlled, Dose-Ranging Clinical Trial

• Published in: The Journal of infectious diseases Vol. 201; no. 6; pp. 814 - 822
• Main Authors: Zolopa, Andrew R., Berger, Daniel S., Lampiris, Harry, Zhong, Lijie, Chuck, Steven L., Enejosa, Jeffrey V., Kearney, Brian P., Cheng, Andrew K.
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.03.2010; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Aged; Antivirals; Biological and medical sciences; Biomedical research; CD4 Lymphocyte Count; Darunavir; Dosage; Drug Resistance, Viral - genetics; Drug Therapy, Combination; Female; Fundamental and applied biological sciences. Psychology; HIV; HIV 1; HIV Infections - blood; HIV Infections - drug therapy; HIV Integrase Inhibitors - pharmacology; HIV Integrase Inhibitors - therapeutic use; HIV Protease Inhibitors - pharmacology; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; HIV-1 - genetics; HIV/AIDS; Human immunodeficiency virus; Human immunodeficiency virus 2; Humans; Infectious diseases; Male; Medical research; Medical sciences; Microbiology; Middle Aged; Miscellaneous; Protease inhibitors; Pyridines - pharmacology; Pyridines - therapeutic use; Pyrones - pharmacology; Pyrones - therapeutic use; Quinolones - pharmacology; Quinolones - standards; Quinolones - therapeutic use; Ritonavir - pharmacology; Ritonavir - therapeutic use; RNA; RNA, Viral - blood; Sulfonamides - pharmacology; Sulfonamides - therapeutic use; Treatment Outcome; Virology; Young Adult; Virus; Infection; Resistance; Antiretroviral agent; Integrase inhibitor; HIV-1 virus; Retroviridae; Antiviral; Elvitegravir; Clinical trial; Human immunodeficiency virus; Lentivirus
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1086/650698

Background. This phase 2, randomized, active-controlled, 48-week study assessed the noninferiority of the human immunodeficiency virus (HIV) integrase inhibitor elvitegravir to comparator ritonavir-boosted protease inhibitor (CPI/r) in treatment-experienced subjects. Methods. Subjects had HIV RNA levels ⩾1000 copies/mL and ⩾1 protease resistance mutation. Subjects received nucleoside or nucleotide reverse-transcriptase inhibitors (NRTIs) with or without T-20 and either CPI/r or once-daily elvitegravir at a dose of 20 mg, 50 mg, or 125 mg (blinded to dose) with ritonavir. After week 8, the independent data monitoring committee stopped the elvitegravir 20 mg arm and allowed subjects in the elvitegravir 50 mg and 125 mg arms to add protease inhibitors. The primary end point was the time-weighted average change from baseline in HIV RNA level through week 24 (DAVG24). Results. A total of 278 subjects with a median of 11 protease and 3 thymidine analog mutations were randomized and treated. One-half of subjects received NRTIs without expected antiviral activity. Compared with the DAVG24 for the CPI/r arm (−1.19 log10 copies/mL), the elvitegravir 50 mg arm was noninferior (−1.44 log10 copies/mL), and the elvitegravir 125 mg arm was superior (−1.66 log10 copies/mL; P=.021). Efficacy was impacted by activity of background agents. There was no relationship between elvitegravir dosage and adverse events. Conclusions. Elvitegravir was well-tolerated and produced rapid virologic suppression that was durable with active background therapy. Trial registration. ClinicalTrials.gov identifier number: NCT00298350.