AIDS. 2009 Nov 13;23(17):2289-300.
Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials.
Katlama C,
Haubrich R,
Lalezari J,
Lazzarin A,
Madruga JV,
Molina JM,
Schechter M,
Peeters M,
Picchio G,
Vingerhoets J,
Woodfall B,
De Smedt G;
DUET-1, DUET-2 study groups.
Ariza HA, Benetucci J, Cahn P, Calanni LM, Cassetti I, Corral J, David DO, Krolewiecki A, Losso MH, Patterson P, Teijeiro RA, Grinsztejn B, da Cunha CA, Kallas EG, Netto EM, Pilotto JH, Suleiman J, Timerman A, Ballesteros J, Northland R, Alvilés Montoya AA, Herrera Martinez G, Solano Chinchilla A, Dupon M, Livrozet JM, Morlat P, Pialoux G, Piketty C, Poizot-Martin I, Andrade-Villanueva J, Reyes-Terán G, Sierra-Madero J, Canton A, Rodriguez A, Sosa N, Morales Ramirez JO, Santana Bagur JL, Soto-Malave R, Anekthananon T, Mootsikapun P, Ruxrungtham K, Albrecht M, Bellos N, Bolan R, Brachman P, Brinson C, Cruickshank F, Elion R, Fessel WJ, Hawkins T, Hodder S, Hutcherson P, Jefferson T, Katner H, Kinder C, Kozal M, Leider J, Mills T, McDonough D, Mounzer K, Nadler J, Norris D, O'Brien W, Pierone G, Raben K, Rashbaum B, Rawlings M, Rodwick B, Ruane P, Sampson J, Schrader S, Scribner A, Sension M, Sweet D, Wade B, Wheeler D, Wilkin A, Wills T, Wohlfeiler M, Workowski K, Chuah J, Cooper D, Eu B, Hoy J, Workman C, Clumeck N, Colebunders R, Moutschen M, Gill J, Gough K, Junod P, Kilby D, Montaner J, Rachlis A, Trottier B, Tsoukas CM, Walmsley SL, Arvieux C, Cotte L, Delfraissy JF, Girard PM, Marchou B, Vittecoq D, Yazdanpanah Y, Yeni P, Arastéh K, Esser S, Fätkenheuer G, Gellermann H, Göbels K, Goebel FD, Jäger H, Moll A, Rockstroh JK, Schuster D, Staszewski S, Stoehr A, Antinori A, Carosi G, Di Perri G, Esposito R, Mazzotta F, Pagano G, Raise E, Rusconi S, Sighinolfi L, Suter F, Frissen PH, Prins JM, Rijnders BJ, Horban A, Antunes F, Miranda M, Vera J, Clotet B, Domingo P, Garcia G, Gatell JM, González-Lahoz J, López-Aldeguer J, Podzamczer D, Easterbrook P, Fisher M, Johnson M, Orkin C, Wilkins E, Barnett B, Baxter J, Beatty G, Berger D, Borkert C, Campell T, Cohen C, Conant M, Ernst J, Farthing C, File T, Frank M, Gallant JE, Greenberg RN, Hicks C, Jayaweera DT, Kerkar S, Markowitz N, Martorell C, McDonald C, McMahon D, Mogyoros M, Myers RA, Richmond G, Sathasivam K, Schneider S, Schrager H, Shalit P, Siegal FP, Sloan L, Smith K, Smith S, Tebas P, Tkatch LS, Towner W.
Source
Université Pierre et Marie Curie, Paris VI and Hôpital Pitié-Salpêtrière, Paris, France. christine.katlama@psl.aphp.fr
Abstract
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.
- PMID:
- 19710593
- [PubMed - indexed for MEDLINE]
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