Darunavir (Prezista)

Published August 09, 2006; Updated October 19, 2011
Susa Coffey, MD
http://hivinsite.ucsf.edu/InSite?page=ar-03-10
Selected References
1. Katlama  C, Esposito  R, Gatell  JM, Goffard  JC, Grinsztejn  B, Pozniak  A, Rockstroh  J, Stoehr  A, Vetter  N, Yeni  P, Parys  W, Vangeneugden  T; the POWER 1 study group.
Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1. AIDS. 2007 Feb;21(4):395-402
[PubMed ID: 17301557]
Abstract:
BACKGROUND: The ongoing phase IIb POWER 1 (TMC114-C213) trial is designed to assess efficacy and safety of the protease inhibitor (PI) TMC114 (darunavir) in treatment-experienced HIV-1-infected patients. DESIGN: This randomized, partially blinded, 24-week dose-finding study compared efficacy and safety of four doses of TMC114 plus low-dose ritonavir (TMC114/r) with investigator-selected control PI(s) (CPI[s]). METHODS: Patients with one or more primary PI mutation and HIV RNA > 1000 copies/ml received optimized background therapy, plus TMC114/r 400/100 mg once daily, 800/100 mg once daily, 400/100 mg twice daily or 600/100 mg twice daily, or CPI(s). The primary endpoint (intent-to-treat) compared proportions of patients achieving viral load reduction >or= 1.0 log10 copies/ml from baseline. RESULTS: In total, 318 patients were treated. Baseline mean viral load was 4.48 log10 copies/ml; median CD4 cell count was 179 cells/microl. In the CPI arm 62% of patients discontinued (virological failure: 54%); 10% of TMC114/r patients discontinued. More TMC114/r (69-77%) than CPI patients (25%) reached the primary endpoint (P < 0.001); 43-53% of TMC114/r patients and 18% of the CPI arm achieved viral load < 50 copies/ml (P < 0.001). TMC114/r demonstrated greater mean CD4 cell count increases versus CPI(s) (68-124 versus 20 cells/microl; P < 0.05). TMC114/r 600/100 mg twice daily demonstrated the highest virological and immunological responses. Adverse event incidence was similar between treatments; headache and diarrhoea were more common with CPI(s). CONCLUSIONS: TMC114/r demonstrated statistically higher 24-week virological response rates and CD4 cell count increases than CPI(s). TMC114/r 600/100 mg twice daily has received regulatory approval in treatment-experienced patients.
2. Haubrich  R, Berger  D, Chiliade  P, Colson  A, Conant  M, Gallant  J, Wilkin  T, Nadler  J, Pierone  G, Saag  M, van Baelen  B, Lefebvre  E; POWER 2 Study Group.
Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients. AIDS. 2007 Mar;21(6):F11-8
[PubMed ID: 17413685]
Abstract:
BACKGROUND: Agents for the treatment of HIV-1-infected patients with resistance to current antiretroviral (ART) drugs are needed. METHODS: TMC114-C202 was a randomized, partially blinded, dose-finding study in treatment-experienced HIV-1-infected patients with one or more primary protease inhibitor (PI) mutations and HIV-1 RNA > 1000 copies/ml. Patients were randomized to receive one of four TMC114 doses given with ritonavir (TMC114/r) or investigator-selected control PI drug(s) (CPI); all received an optimized background regimen. The primary intent-to-treat analysis compared the proportion of patients achieving a >or= 1 log10 copies/ml HIV-1 RNA reduction at week 24 between the treatment arms using the time-to-loss of virological response algorithm. RESULTS: For 278 patients at baseline, mean HIV-1 RNA was 4.7 log10 copies/ml, median CD4 cell count was 106 cells/mul; HIV-1 isolates had a median of three primary PI mutations and a median fold change in lopinavir susceptibility of 80. Discontinuation rates were 23% for TMC114/r versus 64% for CPI. More patients in each TMC114/r dose group achieved >or= 1.0 log10 copies/ml reduction in HIV-1 RNA than in the CPI group (45-62% versus 14%; P <or= 0.003): patients taking TMC114/r twice daily had the greatest responses. HIV-1 RNA was < 50 copies/ml in 18-39% of TMC114/r patients versus 7% CPI (P < 0.001 for highest dose). Mean CD4 cell count increased by 59-75 versus 12 cells/mul (TMC114/r versus CPI: P <or= 0.005). Overall adverse event rates were similar in both arms, without significant differences among TMC114/r groups. CONCLUSIONS: TMC114/r treatment resulted in greater virological and immunological responses in ART-experienced patients compared with CPI at 24 weeks.
3. Katlama C, Berger D, Bellos N, et al. Efficacy of TMC114/r in 3-class experienced patients with limited treatment options: 24-week planned interim analysis of 2 96-week multinational dose-finding trials. In: Program and abstracts of the 12th Conference on Retroviruses and Opportunistic Infections; February 22-25, 2005; Boston. Abstract 164LB.