PMID- 21902621 OWN - NLM STAT- MEDLINE DCOM- 20120717 LR - 20151119 IS - 1931-8405 (Electronic) IS - 0889-2229 (Linking) VI - 28 IP - 5 DP - 2012 May TI - Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb randomized trial. PG - 437-46 LID - 10.1089/AID.2011.0050 [doi] AB - TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected, treatment-naive patients, was extended to investigate long-term safety and efficacy. Week 192 analysis results are presented. This was a long-term follow-up of a Phase IIb, randomized trial. No significant RPV dose-response relationships with respect to the primary endpoint (composite ITT-TLOVR algorithm) were observed at week 48 or 96. All RPV-treated patients were switched to open-label 75 mg qd at week 96 and then to 25 mg qd, the Phase III dose, at approximately week 144 as it gave the best benefit-risk balance. All control patients continued receiving open-label efavirenz (EFV) 600 mg qd. At week 192, 59% of RPV- and 61% of EFV-treated patients maintained confirmed viral load <50 copies/ml (ITT-TLOVR algorithm). The mean changes from baseline in CD4 cell count were similar in both groups (RPV: 210 cells/mm(3) vs. EFV: 225 cells/mm(3)). No new safety concerns were noted between week 48 and 192. In the week 192 analysis, RPV compared with EFV was associated with a lower overall incidence of grade 2-4 adverse events (AEs) at least possibly related to treatment, including rash (p<0.001) and neurologic AEs (p<0.05 Fisher's exact test, post hoc analyses) Incidences of serious AEs, grade 3 or 4 AEs, and discontinuations due to AEs were similar across groups. Increases in total cholesterol, LDL-cholesterol, HDL-cholesterol, and triglycerides were significantly lower with RPV than with EFV. RPV continued to show sustained efficacy similar to EFV at week 192 with a generally more favorable safety profile. FAU - Wilkin, Aimee AU - Wilkin A AD - Wake Forest University Health Sciences, Medical Center Boulevard, Winston-Salem, NC 27157-1042, USA. awilkin@wakehealth.edu FAU - Pozniak, Anton L AU - Pozniak AL FAU - Morales-Ramirez, Javier AU - Morales-Ramirez J FAU - Lupo, Sergio H AU - Lupo SH FAU - Santoscoy, Mario AU - Santoscoy M FAU - Grinsztejn, Beatriz AU - Grinsztejn B FAU - Ruxrungtham, Kiat AU - Ruxrungtham K FAU - Rimsky, Laurence T AU - Rimsky LT FAU - Vanveggel, Simon AU - Vanveggel S FAU - Boven, Katia AU - Boven K CN - TMC278-C204 Study Group LA - eng PT - Clinical Trial, Phase II PT - Clinical Trial, Phase III PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial DEP - 20111017 PL - United States TA - AIDS Res Hum Retroviruses JT - AIDS research and human retroviruses JID - 8709376 RN - 0 (Anti-HIV Agents) RN - 0 (Nitriles) RN - 0 (Pyrimidines) RN - EC 2.7.7.49 (HIV Reverse Transcriptase) RN - FI96A8X663 (Rilpivirine) SB - IM MH - Acquired Immunodeficiency Syndrome/blood/*drug therapy/virology MH - Adult MH - Aged MH - Anti-HIV Agents/administration & dosage/pharmacology/*therapeutic use MH - CD4 Lymphocyte Count MH - Drug Administration Schedule MH - Female MH - Follow-Up Studies MH - HIV Reverse Transcriptase/*antagonists & inhibitors MH - HIV-1/*drug effects MH - Humans MH - Male MH - Middle Aged MH - Nitriles/administration & dosage/pharmacology/*therapeutic use MH - Pyrimidines/administration & dosage/pharmacology/*therapeutic use MH - Rilpivirine MH - Time Factors MH - Treatment Outcome MH - Viral Load/*drug effects MH - Young Adult FIR - Belloso, Waldo IR - Belloso W FIR - Cahn, Pedro IR - Cahn P FIR - Cassetti, Isabel IR - Cassetti I FIR - Casiro, Arnaldo IR - Casiro A FIR - Losso, Marcelo IR - Losso M FIR - Rieger, Armin IR - Rieger A FIR - Vetter, Norbert IR - Vetter N FIR - Cunha, Clovis Arns Da IR - Cunha CA FIR - Gonsalez, Claudio IR - Gonsalez C FIR - Madruga, Jose Valdez IR - Madruga JV FIR - de Jesus Pedro, Rogerio IR - de Jesus Pedro R FIR - Timerman, Artur IR - Timerman A FIR - Xingwang, Li IR - Xingwang L FIR - Wu, Hao IR - Wu H FIR - Girard, Pierre- Marie IR - Girard P FIR - Molina, Jean-Michel IR - Molina JM FIR - Salmon, Dominique IR - Salmon D FIR - Yazdanpanah, Yazdan IR - Yazdanpanah Y FIR - Yeni, Patrick IR - Yeni P FIR - Arasteh, Keikawus IR - Arasteh K FIR - Fatkenheuer, Gerd IR - Fatkenheuer G FIR - Goebel, Frank IR - Goebel F FIR - Rump, Joerg-Andres IR - Rump JA FIR - Gruzdev, Boris IR - Gruzdev B FIR - Kozyrev, Oleg IR - Kozyrev O FIR - Moshkovich, Grigory IR - Moshkovich G FIR - Pronin, Alexander IR - Pronin A FIR - Romanenko, Oleg IR - Romanenko O FIR - Vinogradova, Elena IR - Vinogradova E FIR - Yakovlev, Alexey IR - Yakovlev A FIR - Ive, Prudence IR - Ive P FIR - Miller, Steven IR - Miller S FIR - Mohapi, Lerato IR - Mohapi L FIR - Wood, Robin IR - Wood R FIR - Chetchotisakd, Ploenchan IR - Chetchotisakd P FIR - Supparatpinyo, Khuanchai IR - Supparatpinyo K FIR - Techasathit, Wichai IR - Techasathit W FIR - Vibhagool, Asda IR - Vibhagool A FIR - Avihingsanon, Anchalee IR - Avihingsanon A FIR - Duncombe, Chris IR - Duncombe C FIR - Katabira, Elly IR - Katabira E FIR - Wilkins, Edmund IR - Wilkins E FIR - Bellos, Nicholaos IR - Bellos N FIR - Chiliade, Philippe IR - Chiliade P FIR - Sathasivam, Kunthavi IR - Sathasivam K FIR - Farthing, Charles IR - Farthing C FIR - Nadler, Jeffrey IR - Nadler J FIR - Casanas, Beata IR - Casanas B FIR - Shalit, Peter IR - Shalit P FIR - Steyn, Dewald IR - Steyn D FIR - Thompson, Melanie IR - Thompson M EDAT- 2011/09/10 06:00 MHDA- 2012/07/18 06:00 CRDT- 2011/09/10 06:00 PHST- 2011/09/10 06:00 [entrez] PHST- 2011/09/10 06:00 [pubmed] PHST- 2012/07/18 06:00 [medline] AID - 10.1089/AID.2011.0050 [doi] PST - ppublish SO - AIDS Res Hum Retroviruses. 2012 May;28(5):437-46. doi: 10.1089/AID.2011.0050. Epub 2011 Oct 17.