Antiretroviral activity and safety of once-daily etravirine in treatment-naive HIV-infected adults: 48-week results.
BACKGROUND
Etravirine (ETR), a non-nucleoside reverse transcriptase inhibitor approved for 200 mg twice-daily dosing in conjunction with other antiretrovirals (ARVs), has pharmacokinetic properties which support once-daily dosing.


METHODS
In this single-arm, open-label study, 79 treatment-naive HIV-infected adults were assigned to receive ETR 400 mg plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) 300/200 mg once daily to assess antiviral activity, safety and tolerability. ARV activity at 48 weeks was determined by proportion of subjects with HIV-1 RNA<50 copies/ml (intention-to-treat, missing = failure).


RESULTS
Of 79 eligible subjects, 90% were men, 62% African-American and 29% Caucasian. At baseline, median (Q1, Q3) age was 29 years (23, 44) and HIV-1 RNA 4.52 log10 copies/ml (4.07, 5.04). A total of 69 (87%) completed a week 48 visit and 61 (77%, 95% CI 66%, 86%) achieved HIV-1 RNA<50 copies/ml at week 48. At time of virological failure, genotypic resistance-associated mutations were detected in three participants, two with E138K (one alone and one with additional mutations). Median (95% CI) CD4(+) cell count increase was 163 (136, 203) cells/µl. Fifteen (19.0%) participants reported a new sign/symptom or lab abnormality ≥ Grade 3 and three participants (3.8%) permanently discontinued ETR due to toxicity. Two participants had psychiatric symptoms of any grade. There were no deaths.


CONCLUSIONS
In this study of ARV-naive HIV-positive adults, once-daily ETR with TDF/FTC had acceptable antiviral activity and was well-tolerated. Once-daily ETR may be a plausible option as part of a combination ARV regimen for treatment-naive individuals. ClinicalTrials.gov NCT00959894.
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, USA. mfloris@med.unc.edu.
Michelle A
MA
Floris-Moore
Katie
K
Mollan
Aimee M
AM
Wilkin
Marc A
MA
Johnson
Angela Dm
AD
Kashuba
David A
DA
Wohl
Kristine B
KB
Patterson
Owen
O
Francis
Catherine
C
Kronk
Joseph J
JJ
Eron
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology*; D015497:HIV-1; D006801:Humans; D008297:Male; D009570:Nitriles; D011724:Pyridazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
D019380:Anti-HIV Agents; D015415:Biomarkers; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine