The rate of accumulation of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in patients kept on a virologically failing regimen containing an NNRTI

HIV Medicine

Volumn 13, Issue 1, 2012, Pages 62-72

  Cozzi Lepri, A ^a,b   Paredes, R ^c   Phillips, A N ^a   Clotet, B ^c   Kjaer J ^d   von Wyl, V ^e   Kronborg, G ^f   Castagna, A ^g   Bogner, J R ^h   Lundgren, J D ^d,i  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF MINNESOTA   (United States)

^c HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e UNIVERSITY HOSPITAL ZURICH   (Switzerland)

^f HVIDOVRE HOSPITAL   (Denmark)

^g VITA SALUTE SAN RAFFAELE UNIVERSITY   (Italy)

^h UNIVERSITY OF MUNICH   (Germany)

ⁱ International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health   (Denmark)

Author keywords

Nonnucleoside reverse transcriptase inhibitor mutations; Ongoing viraemia; Poisson regression; Rate of accumulation

Indexed keywords

DIDANOSINE; EFAVIRENZ; ETRAVIRINE; LAMIVUDINE; NEVIRAPINE; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; STAVUDINE; VIRUS RNA;

ADULT; AGED; ANTIVIRAL RESISTANCE; ANTIVIRAL THERAPY; ARTICLE; DRUG EXPOSURE; DRUG SUBSTITUTION; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; FEMALE; GENOTYPE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; MAJOR CLINICAL STUDY; MALE; PRIORITY JOURNAL; RISK ASSESSMENT; VIRUS MUTATION;

ADULT; AGED; ANTI-HIV AGENTS; BENZOXAZINES; DNA MUTATIONAL ANALYSIS; DRUG RESISTANCE, VIRAL; FEMALE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; MUTATION; NEVIRAPINE; PROSPECTIVE STUDIES; REVERSE TRANSCRIPTASE INHIBITORS; VIRAL LOAD; YOUNG ADULT;

EID: 83855164125     PISSN: 14642662     EISSN: 14681293     Source Type: Journal    
DOI: 10.1111/j.1468-1293.2011.00943.x     Document Type: Article

References (34)

1. UNAIDS 2009. Report on the global AIDS epidemic. Available at (accessed 11 March 2011).
2. BHIVA Guidelines for the Treatment of HIV-1 infected adults with antiretroviral therapy (2008). Available at (accessed 11 March 2011).
3. World Health Organization (WHO). Antiretroviral therapy for HIV infection in adults and adolescents: rapid advice 2009. Available at (accessed 11 March 2011).
4. Cozzi-Lepri A, Phillips AN, Martinez-Picado Jet al. for the EuroSIDA Study Group. Rate of accumulation of thymidine analogue mutations in patients continuing to receive virologically failing regimens containing zidovudine or stavudine: implications for antiretroviral therapy programs in resource-limited settings. J Infect Dis 2009; 200: 687-697.
5. Stevens WS. Slow accumulation of HIV resistance mutations: Implications for resource-limited settings? J Infect Dis 2009; 200: 670-672.
6. Ghosn J, Chaix ML, Delaugerre C. HIV-1 resistance to first- and second-generation non-nucleoside reverse transcriptase inhibitors. AIDS Rev 2009; 11: 165-173.
7. Madruga JV, Cahn P, Grinsztejn Bet al. for the DUET-1 study group. Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial. Lancet 2007; 370: 29-38.
8. Lazzarin A, Campbell T, Clotet Bet al. for the DUET-2 study group. 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.
9. Katlama C, Haubrich R, Lalezari Jet al. for the DUET-1, DUET-2 study groups. Efficacy and safety of etravirine in treatment-experienced, HIV-1 patients: pooled 48 week analysis of two randomized, controlled trials. AIDS 2009; 23: 2289-2300.
10. Braitstein P, Zala C, Yip Bet al. Immunologic response to antiretroviral therapy in hepatitis C virus-coinfected adults in a population-based HIV/AIDS treatment program. J Infect Dis 2006; 193: 259-268.
11. Bachani D, Garg R, Rewari BBet al. Two-year treatment outcomes of patients enrolled in India's national first-line antiretroviral therapy programme. Natl Med J India 2010; 23: 7-12.
12. Stringer JS, Zulu I, Levy Jet al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA 2006; 296: 782-793.
13. Geretti AM, Harrison L, Green Het al. for the UK Collaborative Group on HIV Drug Resistance. Effect of HIV-1 subtype on virologic and immunologic response to starting highly active antiretroviral therapy. Clin Infect Dis 2009; 48: 1296-1305.
14. Lundgren JD, Phillips AN, Vella Set al. for the EuroSIDA Study Group. Regional differences in use of antiretroviral agents and primary prophylaxis in 3122 European HIV-infected patients. J Acquir Immune Defic Syndr Hum Retrovirol 1997; 16: 153-160.
15. ©, Leuven, 16 June 2009. Available at (accessed 11 March 2011).
16. Johnson VA, Brun-Vézinet F, Clotet Bet al. Update of the drug resistance mutations in HIV-1: December 2010. Top HIV Med 2010; 18: 156-163.
17. Statistical Analysis Software Version 9, Cary, NC. Available at (accessed 11 March 2011).
18. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986; 42: 121-130.
19. Bangsberg DR, Acosta EP, Gupta Ret al. Adherence-resistance relationships for protease and non-nucleoside reverse transcriptase inhibitors explained by virological fitness. AIDS 2006; 20: 223-231.
20. Bacheler LT, Anton ED, Kudish Pet al. Human immunodeficiency virus type 1 mutations selected in patients failing efavirenz combination therapy. Antimicrob Agents Chemother 2000; 44: 2475-2484.
21. Beerenwinkel N, Drton M.A mutagenetic tree hidden Markov model for longitudinal clonal HIV sequence data. Biostatistics 2007; 8: 53-71.
22. Lee KJ, Dunn D, Gilson Ret al. Treatment switches after viral rebound in HIV-infected adults starting antiretroviral therapy: multicentre cohort study. AIDS 2008; 22: 1943-1950.
23. Hart E, Curtis H, Wilkins E, Johnson M. National review of first treatment change after starting highly active antiretroviral therapy in antiretroviral-naive patients. HIV Med 2007; 8: 186-191.
24. Eyawo O, Fernandes KA, Brandson EKet al. Suboptimal use of HIV drug resistance testing in a universal health-care setting. AIDS Care 2011; 23: 42-51.
25. Gupta RK, Hill A, Sawyer AWet al. Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis. Lancet Infect Dis 2009; 9: 409-417.
26. MacArthur RD, Huppler Hullsiek K, Peng Get al. for the CPCRA 058 Study Team, the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the International Network for Strategic Initiative in Global HIV Trials (INSIGHT). Failing therapy with efavirenz results in significantly fewer mutations limiting to etravirine than failing therapy with nevirapine: on-treatment analyses from the CPCRA FIRST study. XVII International HIV Drug Resistance Workshop. Sitges, Spain, June 2008 [Abstract 129].
27. Marcelin AG, Flandre P, Descamps Det al. for the ANRS AC11 Resistance Study Group. Factors associated with virological response to etravirine in nonnucleoside reverse transcriptase inhibitor-experienced HIV-1-infected patients. Antimicrob Agents Chemother 2010; 54: 72-77.
28. Lapadula G, Calabresi A, Castelnuovo Fet al. Prevalence and risk factors for etravirine resistance among patients failing on non-nucleoside reverse transcriptase inhibitors. Antivir Ther 2008; 13: 601-605.
29. Poveda E, Anta L, Blanco JLet al. for the Resistance Platform of the Spanish AIDS Research Network (ResRIS). Etravirine resistance associated mutations in HIV-infected patients failing efavirenz or nevirapine in the Spanish antiretroviral resistance database. AIDS 2010; 24: 469-471.
30. Scherrer AU, Hasse B, von Wyl Vet al. Prevalence of etravirine mutations and impact on response to treatment in routine clinical care: the Swiss HIV Cohort Study (SHCS). HIV Med 2009; 10: 647-656.
31. Kantor R, Shafer RW, Follansbee Set al. Evolution of resistance to drugs in HIV-1-infected patients failing antiretroviral therapy. AIDS 2004; 18: 1503-1511.
32. Napravnik S, Edwards D, Stewart P, Stalzer B, Matteson E, Eron JJ Jr. HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viremia. J Acquir Immune Defic Syndr 2005; 40: 34-40.
33. Orrell C, Walensky RP, Losina E, Pitt J, Freedberg KA, Wood R. HIV type-1 clade C resistance genotypes in treatment-naive patients and after first virological failure in a large community antiretroviral therapy programme. Antivir Ther 2009; 14: 523-531.
34. Hoffmann CJ, Charalambous S, Sim Jet al. Viremia, resuppression, and time to resistance in human immunodeficiency virus (HIV) subtype C during first-line antiretroviral therapy in South Africa. Clin Infect Dis 2009; 49: 1928-1935.