TMC114 provides durable viral load suppression in treatment-experienced patients: POWER 1 and 2 combined week 48 analysis
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).
[Virological response rates]
| Pooled POWER 1 and 2 virologic response rates|
| || Week 24|| Week 48|
|Efficacy parameter||TMC114/r 600/100mg bid (n=131)||CPI|
|P-value||TMC114/r 600/100mg bid (n=110)||CPI|
|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|
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.
AIDS 2006 - XVI International AIDS Conference
"A.Lazzarin, et al.
TMC114 provides durable viral load suppression in treatment-experienced patients: POWER 1 and 2 combined week 48 analysis.
Oral abstract session:
AIDS 2006 - XVI International AIDS Conference: