Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV Type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial.
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 (DAVG(24)).


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 DAVG(24) for the CPI/r arm (-1.19 log(10) copies/mL), the elvitegravir 50 mg arm was noninferior (-1.44 log(10) copies/mL), and the elvitegravir 125 mg arm was superior (-1.66 log(10) 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.
Div of Infectious Diseases and Geographic Medicine, Stanford University, 300 Pasteur Dr, Rm S-156 GrantBldg, Stanford, CA 94305, USA. azolopa@stanford.edu
Andrew R
AR
Zolopa
Daniel S
DS
Berger
Harry
H
Lampiris
Lijie
L
Zhong
Steven L
SL
Chuck
Jeffrey V
JV
Enejosa
Brian P
BP
Kearney
Andrew K
AK
Cheng
D000293:Adolescent; D000328:Adult; D000368:Aged; D018791:CD4 Lymphocyte Count; D000069454:Darunavir; D024882:Drug Resistance, Viral / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D011753:Pyrones / Q000494:pharmacology / Q000627:therapeutic use; D015363:Quinolones / Q000494:pharmacology* / Q000592:standards / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000494:pharmacology* / Q000627:therapeutic use; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
D019428:HIV Integrase Inhibitors; D017320:HIV Protease Inhibitors; D011725:Pyridines; D011753:Pyrones; D015363:Quinolones; D012367:RNA, Viral; D013449:Sulfonamides; C509700:elvitegravir; D019438:Ritonavir; D000069454:Darunavir; C107201:tipranavir