Literature DB >> 23714781

96-Week resistance analyses of rilpivirine in treatment-naive, HIV-1-infected adults from the ECHO and THRIVE Phase III trials.

Laurence Rimsky1, Veerle Van Eygen, Annemie Hoogstoel, Marita Stevens, Katia Boven, Gaston Picchio, Johan Vingerhoets.   

Abstract

BACKGROUND: In the ECHO/THRIVE 96-week efficacy analysis, the response rate was 78% with rilpivirine (RPV) and efavirenz (EFV) plus two nucleoside/nucleotide reverse transcriptase inhibitors.
METHODS: For resistance analyses, virological failures (VFs) were genotyped and/or phenotyped at baseline and failure.
RESULTS: In the overall 96-week resistance analyses, the proportion of VFs was higher with RPV (96/686, 14%) versus EFV (52/682, 8%), but similar within weeks 48-96 (22/686, 3% versus 16/682, 2%). In genotyped VFs, treatment-emergent non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated mutations (RAMs) were as common with RPV (46/86, 53%) versus EFV (20/42, 48%), but nucleoside/nucleotide reverse transcriptase inhibitor RAMs were more common with RPV (48/86, 56%) than EFV (11/42, 26%). In RPV VFs, E138K+M184I remained the most frequent combination. Among RPV VFs with phenotypic RPV resistance, cross-resistance was observed with nevirapine (16/35, 46%), EFV (30/35, 86%) and etravirine (32/35, 91%). Among patients with baseline viral load (VL)≤100,000 copies/ml, there were fewer VFs (RPV: 28/368, 8%; EFV: 20/329, 6%), fewer VFs with treatment-emergent NNRTI RAMs (RPV: 10/27, 37%; EFV: 6/17, 35%), and less phenotypic resistance to RPV and other NNRTIs, than in patients with baseline VL>100,000 copies/ml (VFs: 68/318, 21% [RPV], 32/353, 9% [EFV]; NNRTI RAMs: 36/59, 61% [RPV], 14/32, 56% [EFV]). Among RPV VFs with baseline VL≤100,000 copies/ml observed within weeks 48-96, only 1/7 had phenotypic resistance to RPV.
CONCLUSIONS: During the second year of treatment in ECHO/THRIVE, few VFs with emerging NNRTI RAMs (no new RPV RAMs) occurred.

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Year:  2013        PMID: 23714781     DOI: 10.3851/IMP2636

Source DB:  PubMed          Journal:  Antivir Ther        ISSN: 1359-6535


  18 in total

1.  Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.

Authors:  George L Melikian; Soo-Yon Rhee; Vici Varghese; Danielle Porter; Kirsten White; Jonathan Taylor; William Towner; Paolo Troia; Jeffrey Burack; Edwin Dejesus; Gregory K Robbins; Kristin Razzeca; Ron Kagan; Tommy F Liu; W Jeffrey Fessel; Dennis Israelski; Robert W Shafer
Journal:  J Antimicrob Chemother       Date:  2013-08-09       Impact factor: 5.790

2.  Effects of rilpivirine, 17β-estradiol and β-naphthoflavone on the inflammatory status of release of adipocytokines in 3T3-L1 adipocytes in vitro.

Authors:  Shalini Behl; Abdu Adem; Arif Hussain; Jaipaul Singh
Journal:  Mol Biol Rep       Date:  2019-03-29       Impact factor: 2.316

Review 3.  Resistance to reverse transcriptase inhibitors used in the treatment and prevention of HIV-1 infection.

Authors:  Nicolas Sluis-Cremer; Mark A Wainberg; Raymond F Schinazi
Journal:  Future Microbiol       Date:  2015-10-30       Impact factor: 3.165

4.  HIV-1 clinical isolates with the E138A substitution in reverse transcriptase show full susceptibility to emtricitabine and other nucleoside reverse transcriptase inhibitors.

Authors:  Danielle P Porter; Rima Kulkarni; Kirsten L White
Journal:  Antimicrob Agents Chemother       Date:  2014-09       Impact factor: 5.191

5.  Rilpivirine versus efavirenz with emtricitabine/tenofovir disoproxil fumarate in treatment-naïve HIV-1-infected patients with HIV-1 RNA ≤100,000 copies/mL: week 96 pooled ECHO/THRIVE subanalysis.

Authors:  Georg Behrens; Bart Rijnders; Mark Nelson; Chloe Orkin; Calvin Cohen; Anthony Mills; Richard A Elion; Simon Vanveggel; Marita Stevens; Laurence Rimsky; David Thorpe; Matthew Bosse; Kirsten White; Lijie Zhong; Jennifer DeMorin; Susan K Chuck
Journal:  AIDS Patient Care STDS       Date:  2014-03-24       Impact factor: 5.078

6.  Competitive fitness assays indicate that the E138A substitution in HIV-1 reverse transcriptase decreases in vitro susceptibility to emtricitabine.

Authors:  Nicolas Sluis-Cremer; Kelly D Huber; Chanson J Brumme; P Richard Harrigan
Journal:  Antimicrob Agents Chemother       Date:  2014-01-13       Impact factor: 5.191

7.  Human Immunodeficiency Virus Type 1 Drug Resistance Mutations Update.

Authors:  Robert W Shafer
Journal:  J Infect Dis       Date:  2017-12-01       Impact factor: 5.226

8.  The connection domain mutation N348I in HIV-1 reverse transcriptase enhances resistance to etravirine and rilpivirine but restricts the emergence of the E138K resistance mutation by diminishing viral replication capacity.

Authors:  Hong-Tao Xu; Susan P Colby-Germinario; Maureen Oliveira; Yingshan Han; Yudong Quan; Veronica Zanichelli; Mark A Wainberg
Journal:  J Virol       Date:  2013-11-13       Impact factor: 5.103

Review 9.  Emtricitabine/rilpivirine/tenofovir disoproxil fumarate single-tablet regimen: a review of its use in HIV infection.

Authors:  Emma D Deeks
Journal:  Drugs       Date:  2014-11       Impact factor: 11.431

10.  Impact of drug resistance-associated amino acid changes in HIV-1 subtype C on susceptibility to newer nonnucleoside reverse transcriptase inhibitors.

Authors:  Adriaan E Basson; Soo-Yon Rhee; Chris M Parry; Ziad El-Khatib; Salome Charalambous; Tulio De Oliveira; Deenan Pillay; Christopher Hoffmann; David Katzenstein; Robert W Shafer; Lynn Morris
Journal:  Antimicrob Agents Chemother       Date:  2014-11-24       Impact factor: 5.191

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