Modulation of K65R selection by zidovudine inclusion: Analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (Study COL40263)

AIDS Research and Human Retroviruses

Volumn 25, Issue 7, 2009, Pages 665-672

  Ross, Lisa ^a   Elion, Richard ^b   Lanier, Randall ^a   Dejesus, Edwin ^c   Cohen, Calvin ^d   Redfield, Robert R ^e   Gathe, Joseph C ^f   Hsu, Ricky K ^g   Yau, Linda ^a   Paulsen, D ^a   Ha, Belinda ^a  

^a GLAXOSMITHKLINE   (United States)

^b GEORGE WASHINGTON UNIVERSITY SCHOOL OF MEDICINE AND HEALTH SCIENCES   (United States)

^c ORLANDO IMMUNOLOGY CENTER   (United States)

^d Community Research Initiative ^*  (United States)

^e UNIVERSITY OF MARYLAND   (United States)

^f Therapeutic Concepts   (United States)

^g ST VINCENT S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR PLUS LAMIVUDINE PLUS ZIDOVUDINE; TENOFOVIR; THYMIDINE; VIRUS RNA;

ADULT; ANTIVIRAL RESISTANCE; ANTIVIRAL SUSCEPTIBILITY; ARTICLE; CLINICAL TRIAL; CONTROLLED STUDY; DRUG EFFICACY; DRUG SAFETY; FEMALE; GENE; GENE MUTATION; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; K65R GENE; MAJOR CLINICAL STUDY; MALE; MULTICENTER STUDY; PHENOTYPE; PLASMA; PRIORITY JOURNAL; WILD TYPE;

ADENINE; ADULT; AMINO ACID SUBSTITUTION; ANTI-HIV AGENTS; DIDEOXYNUCLEOSIDES; DRUG ADMINISTRATION SCHEDULE; DRUG RESISTANCE, MULTIPLE, VIRAL; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; LAMIVUDINE; MALE; MIDDLE AGED; PHOSPHONIC ACIDS; PILOT PROJECTS; RNA, VIRAL; TREATMENT FAILURE; ZIDOVUDINE;

EID: 70349225608     PISSN: 08892229     EISSN: None     Source Type: Journal    
DOI: 10.1089/aid.2008.0302     Document Type: Article

References (24)

1. Sarafianos SG, Hughes SH, and Arnold E: Designing anti-AIDS drugs targeting the major mechanism of HIV-1 RT resistance to nucleoside analog drugs. Int J Biochem Cell Biol 2004;36:1706-1715.
2. Gotte M and Wainberg MA: Biochemical mechanisms involved in overcoming HIV resistance to nucleoside inhibitors of reverse transcriptase. Drug Resist Update 2000;3: 30-38.
3. Naeger LK, Margot NA, and Miller MD: Increased drug susceptibility of HIV-1 reverse transcriptase mutants containing M184V and zidovudine-associated mutations: Analysis of enzyme processivity, chain-terminator removal and viral replication. Antiviral Ther 2001;6:115-126.
4. Boyer PL, Sarafianos SG, Arnold E, et al.: The M184V mutation reduces the selective excision of zidovudine 50monophosphate (AZTMP) by the reverse transcriptase of human immunodeficiency virus type 1. J Virol 2002;76:3248-3256.
5. Miranda LR, Gotte M, Liang F, et al.: The L74V mutation in human immunodeficiency virus type 1 reverse transcriptase counteracts enhanced excision of zidovudine monophosphate associated with thymidine analog resistance mutations. Antimicrob Agents Chemother 2005;49:2648-2656.
6. White KL, Chen JM, Feng JY, et al.: The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. Antiviral Ther 2006;11: 155-163.
7. Parikh UM, Zelina S, Sluis-Cremer N, et al.: Molecular mechanisms of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 reverse transcriptase. AIDS 2007;21:1405-1414.
8. Ross L, Johnson M, Graham N, et al.: The reverse transcriptase codon 69 insertion is observed in nucleoside reverse transcriptase inhibitor-experienced HIV-1-infected individuals, including those without prior or concurrent zidovudine therapy. J Hum Virol 1999;2:290-295.
9. Johnson VA, Brun-Vezinet F, Clotet B, et al.: Update of the drug resistance mutations in HIV-1: Fall 2006. Top HIV Med 2006;14:125-130.
10. Shafer RW, Rhee SY, Pillay D, et al.: HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance. AIDS 2007;21:215-223.
11. Khanlou H, Yeh V, Guyer B, et al.: Early virologic failure in a pilot study evaluating the efficacy of therapy containing once-daily abacavir, lamivudine, and tenofovir DF in treatment-naive HIV-infected patients. AIDS Patient Care STDS 2005;19:135-140.
12. Jemsek J, Hutcherson P, and Harper E: Poor virologic responses and early emergence of resistance in treatment naive, HIV-infected patients receiving a once daily triple nucleoside regimen of didanosine, lamivudine, and tenofovir DF. Program and abstracts of the 11th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 8-11, 2004. Abstract 51.
13. Gallant JE, Rodriguez AE, Weinberg WG, et al.: Early virologic nonresponse to tenofovir, abacavir, and lamivudine in HIV-infected antiretroviral-naive subjects. J Infect Dis 2005; 192:1921-1930.
14. Elion R, Cohen C, DeJesus E, et al.: Once-daily abacavir= lamivudine=zidovudine plus tenofovir for the treatment of HIV-1 infection in antiretroviral-naive subjects: A 48-week pilot study. HIV Clin Trials 2006;7:324-333.
15. Moyle G, Higgs C, Teague A, et al.: An open-label, randomized comparative pilot study of a single-class quadruple therapy regimen versus a 2-class triple therapy regimen for individuals initiating antiretroviral therapy. Antiviral Ther 2006;11:73-78.
16. Sturmer M, Staszewski S, and Doerr HW: Quadruple nucleoside therapy with zidovudine, lamivudine, abacavir and tenofovir in the treatment of HIV. Antiviral Ther 2007;12: 695-703.
17. Gulick RM, Lalama CM, Ribaudo HJ, et al.: Intensification of a triple-nucleoside regimen with tenofovir or efavirenz in HIV-1-infected patients with virological suppression. AIDS 2007;21:813-823.
18. Parikh UM, Bacheler L, Koontz D, et al.: The K65R mutation in human immunodeficiency virus type 1 reverse transcriptase exhibits bidirectional phenotypic antagonism with thymidine analog mutations. J Virol 2006;80:4971-4977.
19. White KL, Margot NA, Wrin T, et al.: Molecular mechanisms of resistance to human immunodeficiency virus type 1 with reverse transcriptase mutations K65R and K65R +M184V and their effects on enzyme function and viral replication capacity. Antimicrob Agents Chemother 2002;46:3437-3446.
20. White KL, Chen JM, Feng JY, et al.: The K65R reverse transcriptase mutation in HIV-1 reverses the excision phenotype of zidovudine resistance mutations. Antiviral Ther 2006;11: 155-163.
21. White KL, Margot NA, Ly JK, et al.: A combination of decreased NRTI incorporation and decreased excision determines the resistance profile of HIV-1 K65R RT. AIDS 2005;19:1751-1760.
22. Wainberg MA, Brenner BG, and Turner D: Changing patterns in the selection of viral mutations among patients receiving nucleoside and nucleotide drug combinations directed against human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 2005;49:1671-1678.
23. Gallant JE, Staszewski S, Pozniak AL, et al.: Efficacy and safety of tenofovir DF vs stavudine in combination therapy in antiretroviral-naive patients: A 3-year randomized trial. JAMA 2004;292:191-201.
24. Miller MD: K65R, TAMs and tenofovir. AIDS Rev 2004;6:22-33.