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doi: 10.1097/QAD.0b013e328013d9d7
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Efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: 24-week results of POWER 1

Katlama, Christinea; Esposito, Robertob; Gatell, Jose Mc; Goffard, Jean-Christophed; Grinsztejn, Beatrize; Pozniak, Antonf; Rockstroh, Jurgeng; Stoehr, Albrechth; Vetter, Norberti; Yeni, Patrickj; Parys, Wimk; Vangeneugden, Tonyk; on behalf of the POWER 1 study group

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From the aHôpital Pitié-Salpêtrière, Paris, France

bPoliclinico di Modena, Modena, Italy

cHospital Clinic Universitary, Barcelona, Spain

dHôpital Universitaire Erasme, Brussels, Belgium

eInstituto de Pesquisa Clinica Evandro Chagas-Fiocruz, Brazil

fChelsea and Westminster Hospital, London, UK

gMediz. Universitätsklinik – Immunologische Ambulanz, Bonn, Germany

hIFI-Institut im AK St. Georg, Hamburg, Germany

iOtto-Wagner-Spital, Interne Lungenabteilung, Vienna, Austria

jHôpital Bichat Paris, Paris, France

kTibotec BVBA, Mechelen, Belgium.

Received 1 September, 2006

Revised 10 October, 2006

Accepted 13 October, 2006

Correspondence to Christine Katlama, Service des Maladies Infectieuses et Tropicales, Hôpital de la Pitié-Salpétrière, 47–83 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France. E-mail:

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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 ≥ 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/μl. 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/μl; 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.

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Protease inhibitors (PIs) have significantly improved the management of HIV infection. However, antiretroviral drug resistance, including multi-drug and cross-resistance, compromises effective long-term therapy. A significant need exists for antiretroviral therapies capable of providing virological suppression, particularly in treatment-experienced HIV patients [1].

The new PI TMC114 (darunavir) is highly active against both wild-type and multi-PI-resistant HIV-1 strains in vitro [2,3] and, in combination with low-dose ritonavir (TMC114/r), demonstrated potent antiviral activity in treatment-experienced patients [4]. TMC114/r 600/100 mg twice daily (b.i.d.) is the recommended dose for treatment-experienced HIV patients.

POWER (Performance Of TMC114/r When evaluated in treatment-Experienced patients with PI Resistance) 1 and 2 (TMC114-C213 and C202) aim to assess the efficacy and safety of TMC114/r versus investigator-selected control PI(s) [CPI(s)] in treatment-experienced patients undergoing virological failure: we report here the pre-planned POWER 1 24-week primary analysis.

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Study design

POWER 1 involves centres in Europe, Australia, Brazil and Canada. The phase IIb 24-week dose-finding phase was randomized, controlled and partially blinded. Prior to randomization, investigators selected an optimized background regimen (OBR) for each patient based on genotypic resistance (VirtualPhenotype; Virco BVBA, Mechelen, Belgium) and treatment history, consisting of two or more nucleoside analogue reverse transcriptase inhibitors (NRTIs; excluding abacavir and investigational NRTIs, except emtricitabine) with or without enfuvirtide. Non-nucleoside analogue reverse transcriptase inhibitors (NNRTIs) were excluded. Patients were stratified by screening viral load (< 20 000 or ≥ 20 000 copies/ml), enfuvirtide use in the OBR and screening primary PI mutation number (1, 2, ≥ 3) [5]. Patients received their OBR plus either CPI(s) (excluding tipranavir and other investigational PIs; atazanavir and fosamprenavir were allowed) (CPI arm), or TMC114/r 400/100 mg once daily (q.d.), 800/100 mg q.d., 400/100 mg b.i.d. or 600/100 mg b.i.d. (blinded for dose not schedule). After the primary analysis cut-off date (1 February 2005), all TMC114/r patients switched to TMC114/r 600/100 mg b.i.d.

OBR and/or CPI(s) alterations were prohibited except for tolerability/toxicity reasons. CPI patients experiencing virological failure (viral load reduction < 0.5 log10 copies/ml from baseline beyond week 12) could ‘roll-over’ to another TMC114/r study.

Discussion with the regulatory authorities led to an amendment of the 24-week primary objective, from evaluation of the dose–response relationship between the TMC114/r dose groups for viral load change from baseline, to comparison of all TMC114/r treatment groups with the CPI arm based on viral load reduction ≥ 1.0 log10 copies/ml from baseline [time-to-loss of virological response (TLOVR) algorithm]. Secondary endpoints included the proportions of patients achieving viral loads < 400 and < 50 copies/ml, viral load and CD4 cell count changes, dose-response, and safety/tolerability.

Viral load was determined using the Roche (Basel, Switzerland) Amplicor HIV-1 monitor. Immunological change was evaluated by absolute and percentage CD4 cell counts. Viral phenotypic (Antivirogram; Virco BVBA, Mechelen, Belgium) and genotypic (VirtualPhenotype Virco BVBA) resistance was determined at screening, days –14 and 1, week 2 and the week 24 or withdrawal visit. Phenotypic data were unavailable at baseline and not used in OBR selection. Adverse events (AEs) and laboratory abnormalities were assessed by clinical evaluations and standard laboratory tests (weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20 and 24) and graded according to a modified AIDS Clinical Trial Group (ACTG) severity grading list [6].

The study protocol was reviewed and approved by the appropriate institutional ethics committees and health authorities, and conducted in accordance with the Declaration of Helsinki. All patients provided written informed consent.

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Study participants

Patients were HIV-infected adults with prior use of two or more NRTIs for at least 3 months, one or more NNRTI in a failing regimen, and one or more PI for at least 3 months (prior enfuvirtide use was allowed), with plasma HIV RNA > 1000 copies/ml and one or more primary PI mutation [5], receiving a stable PI-containing regimen. The proportion of patients with three or more primary PI mutations was limited to 30%.

Exclusion criteria included any currently active AIDS-defining illness, treatment-interruption schedule use at screening, screening investigational antiretroviral use, previous randomization to TMC114 treatment, active liver disease, liver impairment/dysfunction, and acute hepatitis A. Hepatitis B or C co-infected patients were included if their condition was clinically stable and would not require treatment during the study.

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Statistical analysis

The primary efficacy and safety analysis was intent-to-treat (ITT; missing or non-completion equals failure). Immunological change was analysed by last observation carried forward (LOCF). Overall significance was adjusted using the Bonferroni–Holms multiple testing procedure [7] to account for multiple comparisons versus the CPI arm after amending the primary efficacy objective. Statistical analyses were adjusted for the stratification factors. To detect a difference of ≥ 0.5 log10 copies/ml in 24-week viral load between the highest and lowest TMC114/r dose groups (common standard deviation of 1) with 80% power at a significance level of 5% (one-sided), 51 patients were required per treatment group. To account for the effect of dropouts on the primary parameters, 60 patients per group were required for the ITT analysis. The same model was applied to compare secondary endpoints between TMC114/r groups and the CPI arm. All analyses were executed as per the pre-planned statistical analysis plan.

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Baseline disease characteristics

Demographics and baseline disease characteristics were similar between treatment arms (Table 1); 31% had three or more primary PI mutations [5], which increased to 58% after the IAS-USA guidelines update [8]. Baseline median numbers of primary PI and PI resistance-associated mutations were three and eight, respectively. In total, 11% of patients had previously used enfuvirtide. Overall, 193 (63%) patients were resistant to all commercially available PIs, 52 (17%) were sensitive to one PI, and 63 (20%) were sensitive to two or more PIs. The median baseline TMC114 fold-change (FC) in 50% effective concentration was 3.5; for CPIs and the median FC was > 10 (range, 13.4–230.2).

Table 1
Table 1
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The PIs used in the CPI arm were lopinavir (46%), saquinavir (38%), (fos)amprenavir (25%), atazanavir (21%) and indinavir (2%); 68% of PI regimens were single-boosted and 29% were double-boosted with ritonavir.

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Patient disposition

Of 697 patients screened, 318 (255 TMC114/r and 63 CPI) were randomized, treated and included in the analysis; the majority of the 363 screened patients who were not randomized either did not meet the eligibility criteria (224), or exceeded the 30% limit for three or more primary PI mutations (107). Sixteen randomized patients were not included (not treated mainly due to withdrawal of consent).

As per protocol, the primary efficacy analysis was performed when the last of 300 patients reached week 24. By the analysis cut-off date, 301 of the 318 randomized and treated patients had reached week 24 or discontinued; 17 had not reached week 24 and were not included in the analysis but censored at their last visit at which viral load data was available (one patient at week 12; three at week 16; 13 at week 20). Overall, 64 patients (20%) discontinued: 25 (10%) and 39 (62%) TMC114/r and CPI patients, respectively, resulting in considerable treatment exposure decreases in the CPI arm versus the TMC114/r groups. Discontinuations in the CPI arm were mainly due to virological failure [34 patients (54%) versus 11 TMC114/r patients (4%)].

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The primary efficacy endpoint (viral load reduction ≥ 1.0 log10 copies/ml from baseline) was achieved by 46 (77%), 42 (69%), 43 (72%) and 42 (70%) patients receiving TMC114/r 600/100 mg b.i.d., 400/100 mg b.i.d., 800/100 mg q.d. and 400/100 mg q.d., respectively, compared with 15 (25%) patients receiving CPI(s) (P < 0.001; Fig. 1a).

Fig. 1
Fig. 1
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Viral loads < 400 and < 50 copies/ml (Fig. 1b) were achieved by 40 (67%) and 32 (53%) TMC114/r 600/100 mg b.i.d. patients, 42 (69%) and 30 (49%) 400/100 mg b.i.d. patients, 37 (62%) and 29 (48%) 800/100 mg q.d. patients, and 38 (63%) and 26 (43%) 400/100 mg q.d. patients, compared with 15 (25%) and 11 (18%) CPI patients, respectively [P < 0.001 for TMC114/r versus CPI(s)]. Mean viral load reductions from baseline were 2.03, 1.69, 1.83 and 1.78 log10 copies/ml in the TMC114/r 600/100 mg b.i.d., 400/100 mg b.i.d., 800/100 mg q.d., and 400/100 mg q.d. groups, respectively, compared with 0.63 log10 copies/ml in the CPI arm (P < 0.001).

Responses were higher with TMC114/r than CPI(s) across the stratification factors and baseline TMC114 FC (Table 2), although the relatively small patient numbers in these subgroups did not provide sufficient power for conclusive statistical analyses. Across the groups, 19–26 TMC114/r and 18 CPI patients received enfuvirtide for the first time (naive), with 76 to 84% and 39% of patients, respectively, achieving the primary efficacy endpoint (Table 2). Baseline TMC114 FC was the most predictive prognostic factor (P < 0.0001) in a multivariate analysis of covariance on viral load change from baseline at week 24.

Table 2
Table 2
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Mean CD4 cell count increases from baseline at week 24 (LOCF) were 124 (P < 0.001), 71, 75 and 68 cells/μl (P < 0.05) for the TMC114/r 600/100 mg b.i.d., 400/100 mg b.i.d., 800/100 mg q.d. and 400/100 mg q.d. groups, respectively, versus 20 cells/μl in the CPI arm (Fig. 2). CD4 change from baseline in the 600/100 mg b.i.d. group was statistically significantly higher than those observed in the 400/100 mg q.d. (P = 0.006), 800/100 mg q.d. (P = 0.009) and 400/100 mg b.i.d. (P = 0.014) groups (pairwise comparisons). At baseline and week 24, 40% (n = 26) and 72% (n = 43), respectively, of TMC114/r 600/100 mg b.i.d. patients had CD4 cell counts above 200 cells/μl, compared with 49% (n = 31) and 58% (n = 5), respectively, of CPI patients.

Fig. 2
Fig. 2
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The safety analysis included patients who received at least one study medication dose, with treatment-emergent safety data recorded between the first intake and either 2 days after the final intake or at the cut-off date. Overall AE incidences (all grades, regardless of causality), were comparable between patients receiving TMC114/r and CPI(s), despite treatment exposure differences (39.8 and 26.3 weeks, respectively). No relationship between TMC114/r dose and AE incidence or discontinuation was observed. Excluding enfuvirtide-associated injection site reactions, the two most common treatment-emergent AEs (≥ 5% of TMC114/r patients) were headache [17%; 24% with CPI(s)] and diarrhoea [16%; 29% with CPI(s)]. Table 3 shows grade 3 or 4 AEs with incidences ≥ 2% in at least one treatment group (regardless of causality). Overall, 36 TMC114/r patients and nine CPI patients (14% each) reported one or more serious AE, most commonly pneumonia and headache. AEs led to discontinuation in 12 (5%) TMC114/r patients and four (6%) CPI patients.

Table 3
Table 3
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Changes from baseline in most laboratory parameters were comparable across treatment groups. Grade 3–4 triglyceride increases occurred in 7 and 8% of TMC114/r and CPI patients, respectively; grade 3 total cholesterol increases occurred in 4 and 0% of TMC114/r and CPI patients, respectively. Grade 3–4 increases occurred in 1 and 3% of TMC114/r and CPI patients, respectively, for alanine aminotransferase (ALT), and 0.4 and 5% of TMC114/r and CPI patients, respectively, for aspartate aminotransferase (AST). No grade 4 cholesterol, ALT or AST elevations occurred in TMC114/r patients. AE incidences for hepatitis B or C co-infected patients were similar to those of the overall population.

Three (1%) patients receiving TMC114/r died during the study. One patient (2%) in the CPI arm died 2 weeks after the last follow-up visit. The deaths were considered by the investigators to be unrelated to study medication (supported by the Data and Safety Monitoring Board).

The study has been extended from 96 to 144 weeks, with ongoing collection of safety data.

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Long-term results

Updated analyses have been performed following the per-protocol 24-week primary analysis. Data from 65 patients who have received TMC114/r 600/100 mg b.i.d. plus OBR from baseline indicate that efficacy is sustained and remains higher than responses observed with CPI(s) to at least week 48, with 47 (72%) patients achieving the primary parameter and 37 (57%) reaching viral loads < 50 copies/ml, compared with 14 (22%) and nine (14%) of 63 CPI patients, respectively. No new or unforeseen safety issues with TMC114/r treatment were identified (mean treatment exposure 71 weeks).

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After 24 weeks, TMC114/r led to viral load reductions ≥ 1.0 log10 copies/ml in a significantly higher proportion of treatment-experienced HIV patients than CPI(s). Although this has classically been the efficacy benchmark in treatment-experienced patients, the therapeutic goal for this patient population has been redefined as achieving a viral load < 50 copies/ml [9], which is associated with durability of response [10]. This represents perhaps the most stringent measure of virological efficacy, particularly in treatment-experienced patients. In this context, the efficacy of TMC114/r has been demonstrated by 53% of patients receiving TMC114/r 600/100 mg b.i.d. achieving viral loads < 50 copies/ml after 24 weeks, compared with 18% of patients receiving CPI(s). Patients receiving TMC114/r 600/100 mg b.i.d. also had the highest increase in CD4 cell count and increase in the proportion of patients with CD4 cell counts above 200 cells/μl.

AE incidences were comparable between TMC114/r and CPI(s) (except for diarrhoea and headache, which were lower in the TMC114/r groups), with no observed differences in hepatitis B or C co-infected patients, or relationship between TMC114/r dose and AE incidence.

The limitations of this study include the small number of patients receiving the TMC114/r 600/100 mg b.i.d. dose; however, 255 patients were treated with TMC114/r over 24 weeks and all doses demonstrated improved efficacy over CPIs. In addition, similar results were also observed at this dose in the POWER 2 study [11], supporting the selection of the 600/100 mg b.i.d. dose. Despite initial selection of a population where approximately 70% had two or fewer primary PI mutations, the proportion of patients with three or more mutations increased from 31 to 58% after the IAS-USA guidelines update [8] and therefore represents an advanced population. While this paper is limited to reporting 24-week data, this was the per-protocol time of the primary analysis, consistent with guidelines for this patient population.

TMC114/r demonstrated statistically higher virological and immunological responses compared with CPI(s) at 24 weeks. While pairwise comparisons of TMC114/r doses revealed no statistically significant differences for virological response, numerically the greatest responses were observed with TMC114/r 600/100 mg b.i.d. which, combined with its safety and tolerability profile, supported its recent regulatory approval [12]. All patients receiving TMC114/r have been switched to this recommended dose for the ongoing open-label phase of the trial. Ongoing studies will define the efficacy and safety of TMC114/r in other patient populations.

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We would like to thank the patients and their families for their participation and support during this study. Special thanks go to Koen De Backer, Marie-Pierre de Béthune, Sandra De Meyer, Martine De Pauw, Frederic Godderis, Richard Hoetelmans, Jasmine Kestemont, Eric Lefebvre, Monika Peters, Vanitha Sekar, Sabrina Spinosa-Guzman, Paul Stoffels, Ben Van Baelem, Hilde Walgraeve and the TMC114 study team for their contributions. The authors would also like to acknowledge Gardiner-Caldwell Communications, for assistance in outline preparation and collating author contributions. Financial assistance to support this service was provided by Tibotec.

Potential conflict of interest and financial disclosures: P.Y. has received study grants and advisory honoraria from Tibotec. C.K. has had associations with Gilead, Roche, GlaxoSmithKline, Tibotec, Bristol Myers Squibb and Boehringer Ingelheim. B.G. has received lecture fees from Bristol Myers Squibb and Tibotec. J.M.G. has received study grants, advisory honoraria or honoraria for lectures from Gilead, Roche, GlaxoSmithKline, Tibotec, Bristol Myers Squibb, Abbott, Pfizer and Boehringer Ingelheim. R.E., A.S., J.-C.G., A.P., J.R. and N.V. all have no contractual obligations, restrictions or conflicts of interest to disclose. W.P. and T.V. are current employees of Tibotec. All authors have reviewed and approved the final draft of the manuscript.

Sponsorship: Tibotec provided funding for the study and their employees collected the data.

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Study contributors

In addition to the authors, the POWER 1 study group included the following investigators and contributors to the design, conduct and analysis of the study.

Australia: D. Cooper, J. Hoy, P. Martinez and C. Workman; Austria: A. Rieger; Belgium: N. Clumeck, C-M. Farber and F. van Wanzeele; Brazil: C.A. Da Cunha, R. Pedro, F. de Queiroz Telles, A. Timerman and J. Valdez-Madruga; Canada: P. Junod, D. Kilby, J. McLeod, R. O'Brien, A. Rachlis, C Tsoukas and S. Walmsely; France: J-F. Delfraissy, P-M. Girard, A. Lafeuillade, J-M. Molina, F. Raffi, J. Reynes, W. Rozenbaum and D. Vittecoq; Germany: K. Arasteh, H. Carls, S. Esser, H. Jaeger, J-A. Rump, C. K. Schewe, D. Schuster, S. Staszewski and A. Woehrmann; Hungary: D. Bánhegyi; Italy: A. Lazzarin, F. Mazzotta and V. Vullo; Poland: A. Boron-Kaczmarska; Portugal: T. Branco, R. Sarmento-e-Castro and J. Vera; Spain: K. Auirrebengoa, B. Clotet, J. Gonzalez-Lahoz, J. Iribarren, H. Knobel, M. J. Perez-Elias, J. J. Picazo and I. Santos; Switzerland: E. Bernasconi and M. Opravil; UK: C. Leen and E. Wilkins.

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1. Gulick RM. New antiretroviral drugs. Clin Microbiol Infect 2003; 9:186–193.

2. De Meyer S, Azijn H, Surleraux D, Jochmans D, Tahri A, Pauwels R, et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 2005; 49:2314–2321.

3. Koh Y, Nakata H, Maeda K, Ogata H, Bilcer G, Devasamudram T, et al. Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chemother 2003; 47:3123–3129.

4. Arastéh K, Clumeck N, Pozniak A, Lazzarin A, De Meyer S, Muller H, et al. TMC114/ritonavir substitution for protease inhibitor(s) in a non-suppressive antiretroviral regimen: a 14-day proof-of-principle trial. AIDS 2005; 19:943–947.

5. D'Aquila RT, Schapiro JM, Brun-Vezinet F, Clotet B, Conway B, Demeter LM, et al. Drug resistance mutations in HIV-1 (IAS-USA). Top HIV Med 2003; 11:92–96.

6. AIDS Clinical Trials Group. Division of AIDS table for grading severity of adult adverse experiences. Available from: 1992 [Accessed: 17 December 2004].

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8. Johnson VA, Brun-Vezinet F, Clotet B, Conway B, D'Aquila RT, Demeter LM, et al. Update of the drug resistance mutations in HIV-1: 2004. Top HIV Med 2004; 12:119–124.

9. Hammer SM, Saag MS, Schechter M, Montaner JS, Schooley RT, Jacobsen DM, et al. Treatment for adult HIV infection: 2006 recommendations of the International AIDS Society-USA panel. JAMA 2006; 296:827–843.

10. U.S. Department of Health and Human Services (DHHS) 2005 Guidelines. Available from: [Accessed: 6 October 2005].

11. Haubrich R, Berger D, Chiliade P, Colson A, Conant M, Gallant J, et al. Week 24 efficacy and safety of TMC114/ritonavir in treatment-experienced HIV patients: POWER 2. 2006; submitted in parallel to AIDS.

12. Tibotec Inc. PREZISTA™ (darunavir) Prescribing Information. June 2006 [cited September 11 2006]. Available from: [Accessed: 11 September 2006].

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Clinical Infectious Diseases
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Journal of Clinical Pharmacology
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Journal of Infectious Diseases
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Journal of Medicinal Chemistry
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European Journal of Medical Research
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European Journal of Medical Research, 14(3): 136-138.

HIV Clinical Trials
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HIV Clinical Trials
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AIDS Reader
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HIV Clinical Trials
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Pulido, F; Del Pozo, MA; Fernandez-Guerrero, M; Moreno, A; Oteo, JA; Flores, J; Pedrol, E; Torres, R; Padilla, B; Tellez, MJ; Garcia, J; Gonzalez-Garcia, J
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HIV Clinical Trials
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Safety, tolerability, and efficacy of darunavir (TMC114) with low-dose ritonavir in treatment-experienced, hepatitis B or C co-infected patients in POWER 1 and 3
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HIV Clinical Trials, 8(4): 213-220.
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Antimicrobial Agents and Chemotherapy
Factors associated with the selection of mutations conferring resistance to protease inhibitors (PIs) in PI-experienced patients displaying treatment failure on darunavir
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HIV entry inhibitors
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Rapid Communications in Mass Spectrometry
Fast and simultaneous determination of darunavir and eleven other antiretroviral drugs for therapeutic drug monitoring: method development and validation for the determination of all currently approved HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry
ter Heine, R; Aiderden-Los, CG; Rosing, H; Hillebrand, MJX; van Gorp, ECM; Huitema, ADR; Beijnen, JH
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New England Journal of Medicine
Raltegravir with optimized background therapy for resistant HIV-1 infection
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New England Journal of Medicine, 359(4): 339-354.

AIDS Reader
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International Journal of Infectious Diseases
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International Journal of Pharmaceutics
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Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences
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Clinical Validation and Applicability of Different Tipranavir/Ritonavir Genotypic Scores in HIV-1 Protease Inhibitor-Experienced Patients
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Clinical Pharmacokinetics
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Expert Opinion on Pharmacotherapy
Etravirine in combination with darunavir/ritonavir and optimized background regimen results in suppression of HIV replication in treatment-experienced patients
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Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-2: 24-week results from a randomised, double-blind, placebo-controlled trial
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Expert Opinion on Pharmacotherapy
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Journal of Infectious Diseases
Prevalence of darunavir resistance-associated mutations: Patterns of occurrence and association with past treatment
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Drugs of Today
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Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences
HPLC-MS method for the simultaneous quantification of the new HIV protease inhibitor darunavir, and 11 other antiretroviral agents in plasma of HIV-infected patients
D'Avolio, A; Siccardi, M; Sciandra, M; Lorena, B; Bonora, S; Trentini, L; Di Perri, G
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From TMC114 to Darunavir: Five Years of Data on Efficacy
Llibre, JM; Imaz, A; Clotet, B
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Biomedicine & Pharmacotherapy
Safety and durability in a cohort of HIV-1 positive patients treated with once and twice daily darunavir-based therapy (SCOLTA Project)
Menzaghi, B; Ricci, E; Carenzi, L; Parruti, G; Orofino, G; Guastavigna, M; Madeddu, G; Maggi, P; Di Biagio, A; Corsi, P; Penco, G; De Socio, G; Martinelli, C; Vichi, F; Celesia, BM; Franzetti, M; Grosso, C; Molteni, C; Bonfanti, P; Quirino, T
Biomedicine & Pharmacotherapy, 67(4): 293-298.
Early virologic suppression with three-class experienced patients: 24-week effectiveness in the darunavir outcomes study
McKinnell, JA; Lin, H; Nevin, CN; Willig, JH; McFarland, G; Genz, M; Raper, JL; DeLaitsch, LL; Mrus, JM; Klaskala, W; Mugavero, MJ; Saag, MS
AIDS, 23(12): 1539-1546.
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Once-daily darunavir/ritonavir vs. lopinavir/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis
Mills, AM; Nelson, M; Jayaweera, D; Ruxrungtham, K; Cassetti, I; Girard, P; Workman, C; Dierynck, I; Sekar, V; Abeele, CV; Lavreys, L
AIDS, 23(13): 1679-1688.
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Raltegravir, etravirine and r-darunavir combination in adolescents with multidrug-resistant virus
Thuret, I; Chaix, M; Tamalet, C; Reliquet, V; Firtion, G; Tricoire, J; Rabaud, C; Frange, P; Aumaître, H; Blanche, S
AIDS, 23(17): 2364-2366.
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JAIDS Journal of Acquired Immune Deficiency Syndromes
Safety and Efficacy of Darunavir (TMC114) With Low-Dose Ritonavir in Treatment-Experienced Patients: 24-Week Results of POWER 3
Molina, J; Cohen, C; Katlama, C; Grinsztejn, B; Timerman, A; Pedro, Rd; Vangeneugden, T; Miralles, D; Meyer, SD; Parys, W; Lefebvre, E; on Behalf of the TMC114-C208 and -C215 Study Groups,
JAIDS Journal of Acquired Immune Deficiency Syndromes, 46(1): 24-31.
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JAIDS Journal of Acquired Immune Deficiency Syndromes
Pharmacokinetics of Coadministered Ritonavir-Boosted Elvitegravir and Zidovudine, Didanosine, Stavudine, or Abacavir
Ramanathan, S; Shen, G; Hinkle, J; Enejosa, J; Kearney, BP
JAIDS Journal of Acquired Immune Deficiency Syndromes, 46(2): 160-166.
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JAIDS Journal of Acquired Immune Deficiency Syndromes
Efficacy of Once-Daily Darunavir/Ritonavir 800/100 mg in HIV-Infected, Treatment-Experienced Patients With No Baseline Resistance-Associated Mutations to Darunavir
De Meyer, SM; Spinosa-Guzman, S; Vangeneugden, TJ; de Béthune, M; Miralles, GD
JAIDS Journal of Acquired Immune Deficiency Syndromes, 49(2): 179-182.
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JAIDS Journal of Acquired Immune Deficiency Syndromes
Determinants of HIV-1 Genotypic Resistance to Darunavir (TMC114) in a Large Italian Resistance Database (Antiretroviral Resistance Cohort Analysis)
Punzi, G; Zazzi, M; on Behalf of the ARCA Collaborative Group, ; Micheli, V; Meraviglia, P; Trezzi, M; Paolini, E; Giacometti, A; Corsi, P; Pietro, MD; Monno, L; Rusconi, S; Gianotti, N; Adorni, F; Boeri, E; Menzo, S; Gonnelli, A
JAIDS Journal of Acquired Immune Deficiency Syndromes, 46(3): 373-375.
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Back to Top | Article Outline

HIV; TMC114; darunavir; protease inhibitor; treatment-experienced patients; efficacy; safety

© 2007 Lippincott Williams & Wilkins, Inc.


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