Darunavir/r vs lopinavir/r: 96 week resistance results from TITAN study

HIV Treat Bull - 2009 Jan-Feb;10(1/2): 04

Simon Collins, HIV i-Base

The Phase 3 TITAN study has previously reported superiority of darunavir/r (DRV/r) compared to lopinavir/r (LPV/r), with 67.5% vs. 59.5% patients achieving <400 copies/mL (difference 8%, 95% CI 0.1–15.8, p=0.03), in almost 600 treatment-naïve patients.

Virological failure was higher in the LPV/r arm (25.6%, n=76) was higher than in the DRV/r arm (13.8%, n=41).

Primary PI mutationswere found in 25/72 of LPV/r and 7/39 for DRV/r patientswith matchedresistance results (with darunavir/r V32I occured in three patients, I47V and L76V in two patients and M46I, I54L, I54M and L90M in one patient).

NRTI mutations occured in 20/72 the LPV/r arm compared to 4/39 in the DRV/r, with similar proportions of patients loosing phenotypic sensitivity to the study protease inhibitor. The majority of patients failing darunavir/r retained susceptibility to other PIs: amprenavir (31/31), atazanavir (29/30), indinavir (31/32), LPV (33/33), nelfinavir (24/26), saquinavir (31/31) and tipranavir (34/35). Susceptibility to the background NRTIs (20/55 vs. 4/35) or any NRTI (27/66 vs. 7/38) was also reduced in significantly more lopinavir/r patients.

Comment

The differences between darunavir/r and lopinavir/r suggest a greater role for darunavir/r in first-line therapy, and as we went to press once-daily darunavir/r was approved in Europe. The retained phenotypic sensitivity to second-line protease options is encouraging, but this will need confirmation with clinical results.

Reference

De Meyer S et al. Resistance development in virological failures with DRV/r or LPV/r: 96-week analysis of the Phase III TITAN trial in treatment- experienced patients. J Int AIDS Soc 2008, 11(Suppl 1):46 doi:10.1186/1758-2652-11-S1-O46.

2009-02-10
IB2009-01-04

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