Simplification from protease inhibitors to once- or twice-daily raltegravir: the ODIS trial.
BACKGROUND
Raltegravir has demonstrated good antiviral activity and safety profile in twice-daily (bid) dosing. However, its long terminal elimination half-life might allow once-daily (qd) administration.


METHODS
Consecutive HIV-infected individuals at our clinic under protease inhibitor (PI)-based regimens with plasma HIV-RNA <50 copies/mL for > 24 weeks were invited to replace PIs with raltegravir. Patients were randomly assigned to raltegravir 800 mg qd, 400 mg bid, or twice daily for the first 3 months and then once daily.


RESULTS
A total of 222 patients completed 24 weeks of follow-up on raltegravir (149 once-daily arm, 35 twice-daily arm, and 38 twice-daily to once-daily arm). At inclusion, mean CD4+ count was 574±308 cells/µL. Within 24 weeks, 13 (5.9%) patients experienced virological failure: 12 (6.4%) in the once-daily arms, and 1 (2.9%) in the twice-daily arm (P = .18). The rate of virological failure was 16.2% (12/74) in patients with prior nucleoside reverse transcriptase inhibitor (NRTI) resistance but only 0.7% (1/148) in the rest (P < .001).


CONCLUSIONS
A switch from PIs to raltegravir in HIV-infected patients with undetectable plasma HIV-RNA effectively sustains viral suppression, as long as prior NRTI resistance had not been selected. No significant differences were seen when comparing raltegravir twice daily or once daily in this context, although once-daily dosing tended to perform less well.
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Eugenia
E
Vispo
Pablo
P
Barreiro
Ivana
I
Maida
Alvaro
A
Mena
Francisco
F
Blanco
Sonia
S
Rodríguez-Novoa
Judit
J
Morello
Inmaculada
I
Jimenez-Nacher
Juan
J
Gonzalez-Lahoz
Vincent
V
Soriano
D000284:Administration, Oral; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018791:CD4 Lymphocyte Count; D002784:Cholesterol / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D019428:HIV Integrase Inhibitors / Q000008:administration & dosage*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000008:administration & dosage*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D019428:HIV Integrase Inhibitors; D011760:Pyrrolidinones; D012367:RNA, Viral; D014280:Triglycerides; D000068898:Raltegravir Potassium; D002784:Cholesterol