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One of very few articles to investigate the clinical decisions made in routine practice after a resistance test is reported
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Bansi L, Smith C, Phillips A, et al. The impact of HIV drug resistance testing on changes to treatment. AIDS 2011;25:603-610. One of very few articles to investigate the clinical decisions made in routine practice after a resistance test is reported.
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European HIV Drug Resistance Guidelines Panel. European HIV drug resistance guidelines 2009 update. 2009. http://www.europeanaidsclinicalsociety. org/download%20documents/TheEuropeanHIVDrugResistance%20-Guidelines2009.pdf. [Accessed 10 February 2011].
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Lengauer T, Sing T. Bioinformatics-assisted anti-HIV therapy. Nat Rev Microbiol 2006; 4:790-797. (Pubitemid 44420130)
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Development of a didanosine genotypic resistance interpretation system based on large derivation and validation datasets
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This careful statistical analysis revealed mutations that affect response to ddI that expert-based interpretation systems had not taken into account
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Assoumou L, Cozzi-Lepri A, Brun-Vézinet F, et al. Development of a didanosine genotypic resistance interpretation system based on large derivation and validation datasets. AIDS 2010; 24:365-371. This careful statistical analysis revealed mutations that affect response to ddI that expert-based interpretation systems had not taken into account.
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Assoumou, L.1
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Talbot A, Grant P, Taylor J, et al. Predicting tipranavir and darunavir resistance using genotypic, phenotypic, and virtual phenotypic resistance patterns: an independent cohort analysis of clinical isolates highly resistant to all other protease inhibitors. Antimicrob Agents Chemother 2010; 54:2473-2479.
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78149442148
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Using TCEs from the EuResist database, the authors found that a complete treatment history is as powerful as a resistance test in predicting short-term virological response. They suggest this is an encouraging result for settings in which resistance testing may not be available
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Prosperi MC, Rosen-Zvi M, Altmann A, et al. Antiretroviral therapy optimisation without genotype resistance testing: a perspective on treatment history based models. PLoS One 2010; 5:e13753. Using TCEs from the EuResist database, the authors found that a complete treatment history is as powerful as a resistance test in predicting short-term virological response. They suggest this is an encouraging result for settings in which resistance testing may not be available.
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PLoS One
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Prosperi, M.C.1
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19
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This study found that one third of clinicians altered their treatment decision when provided with a report from a therapy optimization program. However, this was largely based on patient details presented retrospectively to clinicians and may not reflect its actual impact
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Larder BA, Revell A, Mican JM, et al. Clinical evaluation of the potential utility of computational modeling as an HIV treatment selection tool by physicians with considerable HIV experience. AIDS Patient Care STDS 2011; 25:29-36. This study found that one third of clinicians altered their treatment decision when provided with a report from a therapy optimization program. However, this was largely based on patient details presented retrospectively to clinicians and may not reflect its actual impact.
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AIDS Patient Care STDS
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Larder, B.A.1
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20
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Zazzi M, Kaiser R, Sönnerborg A, et al. Prediction of response to antiretroviral therapy by human experts and by the EuResist data-driven expert system (the EVE study). HIV Med 2010;12:211-218.
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Goicoechea M, Jain S, Bi L, et al. Abacavir and tenofovir disoproxil fumarate co-administration results in a nonadditive antiviral effect in HIV-1-infected patients. AIDS 2010; 24:707-716.
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This article identified two patterns of viral evolution driving the variants toward either a fast or progressive increase in resistance to RAL. A wide range of resistance levels to RAL (10-770-fold change in IC50 levels) were found
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Canducci F, Marinozzi MC, Sampaolo M, et al.Genotypic/phenotypic patterns of HIV-1 integrase resistance to raltegravir. J Antimicrob Chemother 2010;65:425-433. This article identified two patterns of viral evolution driving the variants toward either a fast or progressive increase in resistance to RAL. A wide range of resistance levels to RAL (10-770-fold change in IC50 levels) were found.
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J Antimicrob Chemother
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Canducci, F.1
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Fransen S, Gupta S, Danovich R, et al. Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. J Virol 2009; 83:11440-11446.
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Ferns RB, Kirk S, Bennett J, et al. The dynamics of appearance and disappearance of HIV-1 integrase mutations during and after withdrawal of raltegravir therapy. AIDS 2009; 23:2159-2164.
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AIDS
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Ferns, R.B.1
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Bennett, J.3
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25
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Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity
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Fun A, Van BK, van Lelyveld SF, et al. Mutation Q95K enhances N155H-mediated integrase inhibitor resistance and improves viral replication capacity. J Antimicrob Chemother 2010; 65:2300-2304.
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Van Lelyveld, S.F.3
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26
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79959343365
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Prevalence and patterns of raltegravir resistance in treated patients in Europe
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[abstract 62] This large European collaborative study quantified the frequency of different mutational patterns observed in patients failing RAL-containing therapy
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Geretti AM, Fearnhill E, Ceccherini-Silberstein F, et al. Prevalence and patterns of raltegravir resistance in treated patients in Europe [abstract 62]. In: International HIV & Hepatitis Virus Drug Resistance Workshop & Curative Strategies; June 2010; Dubrovnik, Croatia. http://www.intmedpress.com/ serveFile.cfm?sUID=c10a93ca-a12a-4ff9-980d-07561299189b. This large European collaborative study quantified the frequency of different mutational patterns observed in patients failing RAL-containing therapy.
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International HIV & Hepatitis Virus Drug Resistance Workshop & Curative Strategies; June 2010; Dubrovnik, Croatia
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Geretti, A.M.1
Fearnhill, E.2
Ceccherini-Silberstein, F.3
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27
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Parry CM, Kohli A, Boinett CJ, et al. Gag determinants of fitness and drug susceptibility in protease inhibitor-resistant human immunodeficiency virus type 1. J Virol 2009; 83:9094-9101.
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Parry, C.M.1
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Boinett, C.J.3
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Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss
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Dam E, Quercia R, Glass B, et al. Gag mutations strongly contribute to HIV-1 resistance to protease inhibitors in highly drug-experienced patients besides compensating for fitness loss. PLoS Pathog 2009; 5:e1000345.
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Gupta RK, Kohli A, McCormick AL, et al. Full-length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS 2010; 24:1651-1655. This article found that wild-type viruses can contribute as much as 14-fold reduction in susceptibility to LPV and that cognate protease can balance this by partially restoring susceptibility.
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Whitcomb JM, Huang W, Fransen S, et al. Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism. Antimicrob Agents Chemother 2007; 51:566-575. (Pubitemid 46185274)
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Whitcomb, J.M.1
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Genotypic tropism testing: Evidence-based or leap of faith?
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An excellent state-of-the-art review of genotypic tropism testing including speculation on future developments
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Harrigan PR, Geretti AM. Genotypic tropism testing: evidence-based or leap of faith? AIDS 2011; 25:257-264. An excellent state-of-the-art review of genotypic tropism testing including speculation on future developments.
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Harrigan, P.R.1
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Current V3 genotyping algorithms are inadequate for predicting X4 co-receptor usage in clinical isolates
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DOI 10.1097/QAD.0b013e3282ef81ea, PII 0000203020070912000001
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Low AJ, Dong W, Chan D, et al. Current V3 genotyping algorithms are inadequate for predicting X4 coreceptor usage in clinical isolates. AIDS 2007; 21:F17-F24. (Pubitemid 47329758)
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Sing T, Low AJ, Beerenwinkel N, et al. Predicting HIV coreceptor usage on the basis of genetic and clinical covariates. Antivir Ther 2007; 12:1097-1106. (Pubitemid 350114990)
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Sing, T.1
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A highly sensitive and specific model for predicting HIV-1 tropism in treatment-experienced patients combining interpretation of V3 loop sequences and clinical parameters
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Sánchez V, Masiá M, Robledano C, et al. A highly sensitive and specific model for predicting HIV-1 tropism in treatment-experienced patients combining interpretation of V3 loop sequences and clinical parameters. J Acquir Immune Defic Syndr 2011; 56:51-58.
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Comparative determination of HIV-1 co-receptor tropism by enhanced sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping
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Prosperi MC, Bracciale L, Fabbiani M, et al. Comparative determination of HIV-1 co-receptor tropism by enhanced sensitivity Trofile, gp120 V3-loop RNA and DNA genotyping. Retrovirology 2010; 30:56.
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Prosperi, M.C.1
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37
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Factors associated with proviral DNA HIV-1 tropism in antiretroviral therapy-treated patients with fully suppressed plasma HIV load: Implications for the clinical use of CCR5 antagonists
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Soulie C, Fourati S, Lambert-Niclot S, et al. Factors associated with proviral DNA HIV-1 tropism in antiretroviral therapy-treated patients with fully suppressed plasma HIV load: implications for the clinical use of CCR5 antagonists. J Antimicrob Chemother 2010; 65:749-751.
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38
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78549289153
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The key finding in this article was that virological responses were consistently similar between Trofile and V3 genotype for patients categorized as R5
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McGovern RA, Thielen A, Mo T, et al. Population-based V3 genotypic tropism assay: a retrospective analysis using screening samples from the A4001029 and MOTIVATE studies. AIDS 2010; 24:2517-2525. The key finding in this article was that virological responses were consistently similar between Trofile and V3 genotype for patients categorized as R5.
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McGovern, R.A.1
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39
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79959352493
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Population-based sequencing of the V3-loop is comparable to the enhanced sensitivity Trofile assay in predicting virologic response to maraviroc of treatment-naive patients in the MERIT trial
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abstract 92
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McGovern R, Dong W, Zhong X, et al. Population-based sequencing of the V3-loop is comparable to the enhanced sensitivity Trofile assay in predicting virologic response to maraviroc of treatment-naive patients in the MERIT trial [abstract 92]. In: 17th Conference on Retroviruses and Opportunistic Infections; February 2010; San Francisco, California. http://www.retroconference. org/2010/Abstracts/39053.htm.
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17th Conference on Retroviruses and Opportunistic Infections; February 2010; San Francisco, California
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McGovern, R.1
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Zhong, X.3
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40
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77954746096
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Improved detection of CXCR4-using HIV by V3 genotyping: Application of population-based and 'deep' sequencing to plasma RNA and proviral DNA
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Swenson LC, Moores A, Low AJ, et al. Improved detection of CXCR4-using HIV by V3 genotyping: application of population-based and 'deep' sequencing to plasma RNA and proviral DNA. J Acquir Immune Defic Syndr 2010; 54:506-510.
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J Acquir Immune Defic Syndr
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Swenson, L.C.1
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Genotypic tropism testing from proviral DNA: Test characteristics and clinical outcome
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Obermeier MJ, Carganico A, Bieniek B, et al. Genotypic tropism testing from proviral DNA: test characteristics and clinical outcome. Antivir Ther 2010; 15 (Suppl 2):A132.
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Antivir Ther
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42
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79955483926
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European guidelines on the clinical management of HIV-1 tropism testing
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[Epub ahead of print]. A consensus statement from an expert group on indications for HIV tropism testing, as well as discussion of some technical issues
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Vandekerckhove LPR, Wensing AMJ, Kaiser R, et al. European guidelines on the clinical management of HIV-1 tropism testing. Lancet Infect Dis 2011 [Epub ahead of print]. A consensus statement from an expert group on indications for HIV tropism testing, as well as discussion of some technical issues.
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Lancet Infect Dis
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Vandekerckhove, L.P.R.1
Wensing, A.M.J.2
Kaiser, R.3
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43
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A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5
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Tilton JC, Wilen CB, Didigu CA, et al. A maraviroc-resistant HIV-1 with narrow cross-resistance to other CCR5 antagonists depends on both N-terminal and extracellular loop domains of drug-bound CCR5. J Virol 2010; 84:10863-10876.
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45
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77950923702
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Antiretroviral drug resistance in HIV-1 infected patients with low-level viraemia
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This article provided the first substantive evidence that genotypic resistance testing at low viral levels may be helpful in clinical management
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Mackie N, Phillips A, Kaye S, et al. Antiretroviral drug resistance in HIV-1 infected patients with low-level viraemia. J Infect Dis 2010; 201:1303-1307. This article provided the first substantive evidence that genotypic resistance testing at low viral levels may be helpful in clinical management.
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J Infect Dis
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Mackie, N.1
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46
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Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection
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Toni TA, Asahchop EL, Moisi D, et al. Detection of human immunodeficiency virus (HIV) type 1 M184V and K103N minority variants in patients with primary HIV infection. Antimicrob Agents Chemother 2009; 53:1670-1672.
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Minority HIV-1 drug resistance mutations are present in antiretroviral treatment-naive populations and associated with reduced treatment efficacy
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Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and adherent patients
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Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes
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Simen BB, Simons JF, Hullsiek KH, et al. Low-abundance drug-resistant viral variants in chronically HIV-infected, antiretroviral treatment-naive patients significantly impact treatment outcomes. J Infect Dis 2009; 199:693-701.
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Low-frequency K103N strengthens the impact of transmitted drug resistance on virologic responses to first-line efavirenz or nevirapine-based highly active antiretroviral therapy
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Geretti AM, Fox ZV, Booth CL, et al. Low-frequency K103N strengthens the impact of transmitted drug resistance on virologic responses to first-line efavirenz or nevirapine-based highly active antiretroviral therapy. J Acquir Immune Defic Syndr 2009; 52:569-573.
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Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients
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The article found that minority drug-resistant HIV-1 variants can be frequently detected in treatment-naive, chronically HIV-1-infected patients. However, most of the patients with minority variants were successfully treated
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Metzner KJ, Rauch P, Braun P, et al. Prevalence of key resistance mutations K65R, K103N, and M184V as minority HIV-1 variants in chronically HIV-1 infected, treatment-naive patients. J Clin Virol 2011; 50:156-161. The article found that minority drug-resistant HIV-1 variants can be frequently detected in treatment-naive, chronically HIV-1-infected patients. However, most of the patients with minority variants were successfully treated.
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Preexisting minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure
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Using a case-control design, the investigators demonstrated a negative impact of pre-existing minority Y181C mutants
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Paredes R, Lalama CM, Ribaudo HJ, et al. Preexisting minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis 2010; 201:662-671. Using a case-control design, the investigators demonstrated a negative impact of pre-existing minority Y181C mutants.
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This article found that minor NNRTI-resistant variants were more prevalent in NNRTI-experienced patients and were associated with reduced virologic response to efavirenz-containing regimens
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Halvas EK, Wiegand A, Boltz VF, et al. Low frequency nonnucleoside reverse-transcriptase inhibitor-resistant variants contribute to failure of efavirenz-containing regimens in treatment-experienced patients. J Infect Dis 2010; 201:672-680. This article found that minor NNRTI-resistant variants were more prevalent in NNRTI-experienced patients and were associated with reduced virologic response to efavirenz-containing regimens.
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Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing
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Using a highly sensitive UDPS protocol, pre-existing drug resistance was infrequently observed; only M184I, T215A, and T215I were detected at very low levels. Similarly, drug-resistant variants in plasma quickly decreased to undetectable levels after treatment interruption
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Hedskog C, Mild M, Jernberg J, et al. Dynamics of HIV-1 quasispecies during antiviral treatment dissected using ultra-deep pyrosequencing. PLoS One 2010; 5:e11345. Using a highly sensitive UDPS protocol, pre-existing drug resistance was infrequently observed; only M184I, T215A, and T215I were detected at very low levels. Similarly, drug-resistant variants in plasma quickly decreased to undetectable levels after treatment interruption.
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