Volume 11 Supplement 1

Abstracts of the Ninth International Congress on Drug Therapy in HIV Infection

Open Access

Phase III TITAN week 96 final analysis: efficacy/safety of darunavir/r (DRV/r) vs. lopinavir/r (LPV/r) in LPV-naïve, treatment-experienced patients

  • D Bánhegyi1,
  • C Katlama2,
  • C Da Cunha3,
  • S Schneider4,
  • A Rachlis5,
  • O Romanenko6,
  • C Workman7,
  • A Vandevoorde8,
  • F Tomaka9,
  • T Vangeneugden8 and
  • S Spinosa-Guzman8
Journal of the International AIDS Society200811(Suppl 1):P22

https://doi.org/10.1186/1758-2652-11-S1-P22

Published: 10 November 2008

Background

The primary and secondary end-points of TITAN were met: at week (wk) 48, significantly more DRV/r than LPV/r patients (pts) had VL <400 cp/mL (77 vs. 68%; diff. 9%, 95% CI 2 – 16%; PP non-inferiority p < 0.001; ITT superiority p = 0.008). Final wk 96 data are shown.

Methods

Treatment-experienced, LPV-naïve, HIV-1-infected pts (VL>1,000 cp/mL) on stable HAART or off-treatment for ≥12 wks were randomised to DRV/r 600/100 mg BID, or LPV/r 400/100 mg BID, + OBR (≥2 NRTIs/NNRTIs) for 96 wks.

Summary of results

595 pts enrolled (79% male; median 40 yrs; mean baseline VL 4.30 log10cp/mL; median CD4 232 cells/mm3); 31.4% were PI-naïve; 81.8% susceptible to ≥4 PIs. At wk 96, significantly more DRV/r than LPV/r pts achieved VL<400 cp/mL (66.8% vs. 58.9% [ITT-TLOVR]; diff. 7.9%, 95% CI 0.1 – 15.6), confirming non-inferiority (p < 0.001) and superiority of DRV/r over LPV/r (p = 0.034). At wk 96, 60.4% of DRV/r pts achieved VL<50 cp/mL compared to 55.2% of LPV/r pts (ITT-TLOVR; diff. 5.2%, 95% CI -2.8 – 13.1). Virologic failure (VF; defined as >400 cp/mL) was less frequent with DRV/r compared to LPV/r (13.8 vs. 25.6%). Median CD4 increase was 81 and 93 cells/mm3 for DRV/r and LPV/r groups, respectively. Significantly more DRV/r than LPV/r pts with ≥1 baseline primary PI mutation achieved VL<50 cp/ml (68.0 vs. 37.6%; diff 30.4%, 95% CI 16.4 – 43.3; p < 0.001). The same was true in pts with previous use of ≥1 PI (62.3 vs. 49.0%; diff 13%, 95% CI 3.6 – 22.6; p < 0.007). The incidence of treatment-related diarrhea of at least moderate intensity (≥Grade 2) was lower in DRV/r pts compared with LPV/r pts (8.1 vs. 15.2%, p = 0.007). Rash was more common in DRV/r pts (3.4 vs. 1.0%) but infrequently led to discontinuation (1%). Most Grade 2 to 4 adverse events (AEs), at least possibly related to DRV/r or LPV/r, occurring in ≤1% pts during therapy, were comparable between groups. Serious AEs were reported for 13.8% (DRV/r) and 16.5% (LPV/r) of pts. The incidence of AEs leading to discontinuation was low (8.1% both groups). Changes in triglycerides and total cholesterol from baseline were less pronounced in DRV/r pts.

Conclusion

In this final 96-wk analysis, the primary end-point was maintained, showing non-inferiority and superiority to LPV/r in virologic response. DRV/r pts were half as likely to experience virologic failure and showed more favourable GI and lipid profiles than LPV/r pts. Rash was more common in DRV/r pts than LPV/r pts, but infrequently led to discontinuations.

Authors’ Affiliations

(1)
Szent László Hospital
(2)
Département des Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière
(3)
Centro Medico Sao Francisco
(4)
Living Hope Clinical Foundation
(5)
University of Toronto
(6)
Republican Centre for AIDS and Infectious Diseases Prevention
(7)
Ground Zero Medical Centre
(8)
Tibotec BVBA
(9)
Tibotec Inc., Yardley

Copyright

© Bánhegyi et al; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd.

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