Browsing by Author "Peeters, Monika"

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    Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials
    (2009) Katlama, Christine; Haubrich, Richard; Lalezari, Jacob; Lazzarin, Adriano; Madruga, Jose V.; Molina, Jean-Michel; Schechter, Mauro; Peeters, Monika; Picchio, Gaston; Vingerhoets, Johan; Woodfall, Brian; De Smedt, Goedele; DUET-1; DUET-2 study groups
    Objective: To evaluate the efficacy, safety and virologic resistance profile of etravirine (TMC125), a next-generation nonnucleoside reverse transcriptase inhibitor, over 48 weeks in treatment-experienced adults infected with HIV-1 strains resistant to a nonnucleoside reverse transcriptase inhibitor and other antiretrovirals. Design: DUET-1 (NCT00254046) and DUET-2 (NCT00255099) are two identically designed, randomized, double-blind phase III trials. Methods: Patients received twice-daily etravirine 200 mg or placebo, each plus a background regimen of darunavir/ritonavir, investigator-selected nucleoside/nucleotide reverse transcriptase inhibitors and optional enfuvirtide. Eligible patients had documented nonnucleoside reverse transcriptase inhibitor resistance, at least three primary protease inhibitor mutations at screening and were on a stable but virologically failing regimen for at least 8 weeks, with plasma viral load more than 5000 copies/ml. Pooled 48-week data from the two trials are presented. Results: Patients (1203) were randomized and treated (n = 599, etravirine; n = 604, placebo). Significantly more patients in the etravirine than in the placebo group achieved viral load less than 50 copies/ml at week 48 (61 vs. 40%, respectively; P < 0.0001). Significantly fewer patients in the etravirine group experienced at least one confirmed or probable AIDS-defining illness/death (6 vs. 10%; P = 0.0408). Safety and tolerability in the etravirine group was comparable to the placebo group. Rash was the only adverse event to occur at a significantly higher incidence in the etravirine group (19 vs. 11%, respectively, P < 0.0001), occurring primarily in the second week of treatment. Conclusion: At 48 weeks, treatment-experienced patients receiving etravirine plus background regimen had statistically superior and durable virologic responses (viral load less than 50 copies/ml) than those receiving placebo plus background regimen, with comparable tolerability and no new safety signals reported since week 24.
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    Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial
    (2007) Madruga, Jose Valdez; Cahn, Pedro; Grinsztejn, Beatriz; Haubrich, Richard; Lalezari, Jacob; Mills, Andrew; Pialoux, Gilles; Wilkin, Timothy; Peeters, Monika; Vingerhoets, Johan; de Smedt, Goedele; Leopold, Ludovic; Trefiglio, Ronald; Woodfall, Brian; DUET-1 study group
    Background: Antiretroviral agents active against drug-resistant HIV-1 are needed for treatment-experienced patients. The aim of this trial was to assess the efficacy, safety, and tolerability of TMC125 (etravirine), a non-nucleoside reverse transcriptase inhibitor (NNRTI). Methods: DUET-1 is a continuing, multinational randomised, double-blind, placebo-controlled, phase III trial. Treatment-experienced adult patients with virological failure on stable antiretroviral therapy, documented genotypic evidence of NNRTI resistance, viral load over 5000 copies per mL, and three or more primary protease inhibitor mutations were randomly assigned to receive 200 mg TMC125 or placebo twice daily. All patients also received darunavir with low-dose ritonavir and investigator-selected nucleoside reverse transcriptase inhibitors. Enfuvirtide use was optional. The primary endpoint was a confirmed viral load below 50 copies per mL at week 24 (FDA time-to-loss of virological response algorithm). Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, with the number NCT00254046. Findings: 612 patients were randomised and treated (304 in the TMC125 group, 308 in the placebo group). By week 24, 42 (14%) patients in the TMC125 group and 56 (18%) in the placebo group had discontinued, mainly due to virological failure. At week 24, 170 (56%) patients in the TMC125 group and 119 (39%) patients in the placebo group achieved a confirmed viral load of less than 50 copies per mL (difference in response rates 17%; 95% CI 9-25; p=0.005). Most adverse events were mild or moderate in severity. The type and incidence of adverse events, including neuropsychiatric events, seen with TMC125 were generally comparable with placebo, with the exception of rash (61 [20%] patients on TMC125 vs 30 [10%] on placebo) and diarrhoea (36 [12%] patients on TMC125 vs 63 [20%] on placebo). Interpretation: In treatment-experienced patients with NNRTI resistance, treatment with TMC125 achieved better virological suppression at week 24 than did placebo. The safety and tolerability profile of TMC125 was generally comparable with placebo.
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    The impact of baseline characteristics on virologic response to etravirine: 48-Week pooled analysis of DUET-1 and DUET-2
    (2010) Cahn, Pedro; Haubrich, Richard; Katlama, Christine; Goebel, Frank; Suter, Fredy; Peeters, Monika; Vingerhoets, Johan; Sinha, Rekha; Witek, James
    Aims: The impact of baseline characteristics on response to the non-nucleoside reverse transcriptase inhibitor etravirine was investigated at 48 weeks in the Phase III DUET trials. Methods: Logistic regression was used to examine the effect of baseline demographics, disease characteristics and characteristics of antiretroviral therapy on virologic response (viral load <50 HIV-1 RNA copies/ml) to etravirine in pre-specified pooled subgroup analyses. Results: Several nondemographic characteristics were significant predictors of response in univariate analyses. Baseline viral load, adherence to study medication and use of enfuvirtide were predictive of response in the multivariate analysis. Patients treated with etravirine consistently achieved higher response rates than placebo-treated patients. Conclusions: The clinical benefits of etravirine in the DUET trials were observed irrespective of baseline characteristics.