Abstract

TMC114 provides durable viral load suppression in treatment-experienced patients: POWER 1 and 2 combined week 48 analysis

A. Lazzarin¹, F. Queiroz-Telles², I. Frank³, J. Rockstroh⁴, S. Walmsley⁵, E. De Paepe⁶, T. Vangeneugden⁶, S. Spinosa-Guzman⁶, E. Lefebvre⁷

¹Clinic of Infectious Diseases, Milano, Italy, ²Universidade Federal de Paraná, Parana, Brazil, ³University of Pennsylvania, Philadelphia, United States, ⁴University Hospital, Bonn, Germany, ⁵University Health Network, Toronto General Hospital, Toronto, Canada, ⁶Tibotec BVBA, Mechelen, Belgium, ⁷Tibotec Inc., Yardley, United States

Background: In the POWER 1 (TMC114-C213) and 2 (TMC114-C202) 24-week primary analysis, TMC114 (darunavir) with low-dose ritonavir (TMC114/r) demonstrated better antiviral activity than control PIs (CPIs) in treatment-experienced patients. The highest dose (600/100mg bid) provided the greatest virologic response. The combined 48-week analysis of these trials assesses long-term efficacy and safety of TMC114/r 600/100mg bid versus CPIs.

Methods: In both trials, PI-, NRTI- and NNRTI-experienced patients with ³1 baseline primary PI mutation were randomized to receive an optimized background regimen plus one of four TMC114/r doses or boosted CPI. Virologic response and adverse events (AEs) in patients initially randomized to TMC114/r 600/100mg bid and CPIs were compared at Week 48 (ITT-TLOVR). The primary efficacy parameter was the proportion of patients with ³1 log10 viral load reduction.

Results: At the recommended dose for treatment-experienced patients, TMC114/r achieved significantly higher virologic response rates than CPIs at Week 48, similar to those observed at Week 24 (table).

Pooled POWER 1 and 2 virologic response rates
	Week 24			Week 48
Efficacy parameter	TMC114/r 600/100mg bid (n=131)	CPI (n=124)	P-value	TMC114/r 600/100mg bid (n=110)	CPI (n=120)	P-value
Patients with HIV RNA >=1.0 log10 reduction (%)	70	21	<0.001	61	15	<0.001
Patients with HIV RNA <50 copies/mL (%)	45	12	<0.001	46	10	<=0.003
Mean HIV RNA log10 reduction (copies/mL)	–1.89	–0.48	<0.001	–1.63	–0.35	<0.001
Mean CD4 increase (cells/mm3)	92	17	<0.001	102	19	<=0.005

[Virological response rates]

The most commonly reported AEs during TMC114/r 600/100mg bid treatment were diarrhea (20%), nausea (18%), headache (15%), nasopharyngitis (14%) and fatigue (12%), reported in 28%, 13%, 20%, 11% and 17% of CPI patients, respectively. The majority of AEs were grade 1–2 in severity.

Conclusions: TMC114/r has demonstrated sustained efficacy in this treatment-experienced population. Its tolerability profile is similar to that of CPIs, with a lower incidence of diarrhea.

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