Rilpivirine and doravirine have complementary efficacies against NNRTI-resistant HIV-1 mutants

Journal of Acquired Immune Deficiency Syndromes

Volumn 72, Issue 5, 2016, Pages 485-491

  Smith, Steven J ^a   Pauly, Gary T ^a   Akram, Aamir ^a   Melody, Kevin ^b   Ambrose, Zandrea ^b,c   Schneider, Joel P ^a   Hughes, Stephen H ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

^b UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^c UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

antiviral activity; HIV 1; non nucleoside reverse transcriptase inhibitor; potency; resistance; susceptibility

Indexed keywords

DORAVIRINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; RILPIVIRINE; PYRIDONE DERIVATIVE; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; TRIAZOLE DERIVATIVE;

ANTIVIRAL ACTIVITY; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CONTROLLED STUDY; DRUG BINDING SITE; DRUG POTENCY; DRUG POTENTIATION; HUMAN IMMUNODEFICIENCY VIRUS 1; IC50; NONHUMAN; PRIORITY JOURNAL; VIRUS MUTANT; VIRUS MUTATION; ANTIVIRAL RESISTANCE; DOSE RESPONSE; DRUG EFFECTS; GENETICS; HIV INFECTIONS; HUMAN; METABOLISM; MOLECULAR MODEL; MUTATION; VIROLOGY; VIRUS REPLICATION;

DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, VIRAL; HIV INFECTIONS; HIV REVERSE TRANSCRIPTASE; HIV-1; HUMANS; INHIBITORY CONCENTRATION 50; MODELS, MOLECULAR; MUTATION; PYRIDONES; REVERSE TRANSCRIPTASE INHIBITORS; RILPIVIRINE; TRIAZOLES; VIRUS REPLICATION;

EID: 84966478660     PISSN: 15254135     EISSN: 10779450     Source Type: Journal    
DOI: 10.1097/QAI.0000000000001031     Document Type: Article

References (27)

1. Das K, Arnold E. HIV-1 reverse transcriptase and antiviral drug resistance. Part 1. Curr Opin Virol. 2013; 3: 111-118
2. Das K, Arnold E. HIV-1 reverse transcriptase and antiviral drug resistance. Part 2. Curr Opin Virol. 2013; 3: 119-128
3. Spence RA, Kati WM, Anderson KS, et al. Mechanism of inhibition of HIV-1 reverse transcriptase by nonnucleoside inhibitors. Science. 1995; 267: 988-993
4. Rittinger K, Divita G, Goody RS. Human immunodeficiency virus reverse transcriptase substrate-induced conformational changes and the mechanism of inhibition by nonnucleoside inhibitors. Proc Natl Acad Sci U S A. 1995; 92: 8046-8049
5. Das K, Martinez SE, Bauman JD, et al. HIV-1 reverse transcriptase complex with DNA and nevirapine reveals non-nucleoside inhibition mechanism. Nat Struct Mol Biol. 2012; 19: 253-259
6. Shirasaka T, Kavlick MF, Ueno T, et al. Emergence of human immunodeficiency virus type 1 variants with resistance to multiple dideoxynucleosides in patients receiving therapy with dideoxynucleosides. Proc Natl Acad Sci U S A. 1995; 92: 2398-2402
7. Das K, Lewi PJ, Hughes SH, et al. Crystallography and the design of anti-AIDS drugs: conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors. Prog Biophys Mol Biol. 2005; 88: 209-231
8. Das K, Clark AD, Jr., Lewi PJ, et al. Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem. 2004; 47: 2550-2560
9. Janssen PA, Lewi PJ, Arnold E, et al. In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (R278474, rilpivirine). J Med Chem. 2005; 48: 1901-1909
10. Azijn H, Tirry I, Vingerhoets J, et al. TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1. Antimicrob Agents Chemother. 2010; 54: 718-727
11. Lazzarin A, Campbell T, Clotet B, et al. 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. Lancet. 2007; 370: 39-48
12. Cohen CJ, Molina JM, Cahn P, et al. Efficacy and safety of rilpivirine (TMC278) versus efavirenz at 48 weeks in treatment-naive HIV-1-infected patients: pooled results from the phase 3 double-blind randomized ECHO and THRIVE trials. J Acquir Immune Defic Syndr. 2012; 60: 33-42
13. Rimsky L, Vingerhoets J, Van Eygen V, et al. Genotypic and phenotypic characterization of HIV-1 isolates obtained from patients on rilpivirine therapy experiencing virologic failure in the phase 3 ECHO and THRIVE studies: 48-week analysis. J Acquir Immune Defic Syndr. 2012; 59: 39-46
14. Cohen CJ, Andrade-Villanueva J, Clotet B, et al. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial. Lancet. 2011; 378: 229-237
15. Xu HT, Asahchop EL, Oliveira M, et al. Compensation by the E138K mutation in HIV-1 reverse transcriptase for deficits in viral replication capacity and enzyme processivity associated with the M184I/V mutations. J Virol. 2011; 85: 11300-11308
16. Lai MT, Feng M, Falgueyret JP, et al. In vitro characterization of MK-1439, a novel HIV-1 nonnucleoside reverse transcriptase inhibitor. Antimicrob Agents Chemother. 2014; 58: 1652-1663
17. Feng M, Wang D, Grobler JA, et al. In vitro resistance selection with doravirine (MK-1439), a novel nonnucleoside reverse transcriptase inhibitor with distinct mutation development pathways. Antimicrob Agents Chemother. 2015; 59: 590-598
18. Marinello J, Marchand C, Mott BT, et al. Comparison of raltegravir and elvitegravir on HIV-1 integrase catalytic reactions and on a series of drug-resistant integrase mutants. Biochemistry. 2008; 47: 9345-9354
19. Smith SJ, Hughes SH, Rapid screening of HIV reverse transcriptase and integrase inhibitors. J Vis Exp. 2014 86
20. Johnson BC, Pauly GT, Rai G, et al. A comparison of the ability of rilpivirine (TMC278) and selected analogues to inhibit clinically relevant HIV-1 reverse transcriptase mutants. Retrovirology. 2012; 9: 99
21. Smith SJ, Pauly GT, Akram A, et al. Rilpivirine analogs potently inhibit drug-resistant HIV-1 mutants. Retrovirology. 2016; 13: 11
22. Das K, Bauman JD, Clark AD, et al. High-resolution structures of HIV-1 reverse transcriptase/TMC278 complexes: strategic flexibility explains potency against resistance mutations. Proc Natl Acad Sci U S A. 2008; 105: 1466-1471
23. Das K, Bandwar RP, White KL, et al. Structural basis for the role of the K65R mutation in HIV-1 reverse transcriptase polymerization, excision antagonism, and tenofovir resistance. J Biol Chem. 2009; 284: 35092-35100
24. Hare S, Smith SJ, Metifiot M, et al. Structural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572). Mol Pharmacol. 2011; 80: 565-572
25. Kobayashi M, Yoshinaga T, Seki T, et al. In Vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011; 55: 813-821
26. Margolis AM, Heverling H, Pham PA, et al. A review of the toxicity of HIV medications. J Med Toxicol. 2014; 10: 26-39
27. Stolbach A, Paziana K, Heverling H, et al. A Review of the toxicity of HIV medications II: interactions with drugs and complementary and alternative medicine products. J Med Toxicol. 2015; 11: 326-341