viral drug resistance


Summary: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.

Top Publications

  1. Jakobsen M, Tolstrup M, Søgaard O, Jørgensen L, Gorry P, Laursen A, et al. Transmission of HIV-1 drug-resistant variants: prevalence and effect on treatment outcome. Clin Infect Dis. 2010;50:566-73 pubmed publisher
    ..Therefore, the clinical relevance of low-abundance resistant quasispecies in early infection is still in question. ..
  2. Esposito S, Molteni C, Colombo C, Daleno C, Dacco V, Lackenby A, et al. Oseltamivir-induced resistant pandemic A/H1N1 influenza virus in a child with cystic fibrosis and Pseudomonas aeruginosa infection. J Clin Virol. 2010;48:62-5 pubmed publisher
    ..Zanamivir inhalation can be successfully used in patients with cystic fibrosis without causing adverse respiratory events, highlighting that the risks and benefits of this drug must be considered on a patient by patient basis. ..
  3. Mouscadet J, Tchertanov L. Raltegravir: molecular basis of its mechanism of action. Eur J Med Res. 2009;14 Suppl 3:5-16 pubmed
    ..In this review, we describe the mechanism of action of this drug and the main data relating to its use in vivo, together with recent structural data important to our understanding of the origin of viral resistance. ..
  4. Paredes R, Lalama C, Ribaudo H, Schackman B, Shikuma C, Giguel F, et al. Pre-existing minority drug-resistant HIV-1 variants, adherence, and risk of antiretroviral treatment failure. J Infect Dis. 2010;201:662-71 pubmed publisher
    ..In adherent patients, pre-existing minority Y181C mutants more than tripled the risk of virologic failure of first-line efavirenz-based antiretroviral therapy. NCT00013520. ..
  5. Clavel F. HIV resistance to raltegravir. Eur J Med Res. 2009;14 Suppl 3:47-54 pubmed
  6. Halvas E, Wiegand A, Boltz V, Kearney M, Nissley D, Wantman M, 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;201:672-80 pubmed publisher
    ..5 vs -1.1 log(10) copies/mL; P < .001). Minor NNRTI-resistant variants were more prevalent in NNRTI-experienced patients and were associated with reduced virologic response to efavirenz-containing multidrug regimens. ..
  7. Chen H, Cheung C, Tai H, Zhao P, Chan J, Cheng V, et al. Oseltamivir-resistant influenza A pandemic (H1N1) 2009 virus, Hong Kong, China. Emerg Infect Dis. 2009;15:1970-2 pubmed publisher
    ..Investigations showed a resistant virus with the neuraminidase (NA) 274Y genotype in quasi-species from a nasopharyngeal aspirate. Monitoring for the naturally occurring NA 274Y mutation in this virus is necessary. ..
  8. Wang B, Dwyer D, Blyth C, Soedjono M, Shi H, Kesson A, et al. Detection of the rapid emergence of the H275Y mutation associated with oseltamivir resistance in severe pandemic influenza virus A/H1N1 09 infections. Antiviral Res. 2010;87:16-21 pubmed publisher
    ..In the light of emerging resistance, close monitoring and understanding of the nature and dynamics of resistance mutations in newly emerging strains should be a priority...
  9. Baz M, Abed Y, Simon P, Hamelin M, Boivin G. Effect of the neuraminidase mutation H274Y conferring resistance to oseltamivir on the replicative capacity and virulence of old and recent human influenza A(H1N1) viruses. J Infect Dis. 2010;201:740-5 pubmed publisher
    ..The viral fitness of the recent A/Brisbane/59/2007-like H274Y variant is not impaired, consistent with its global dissemination. These results reinforce the need for new antiviral strategies. ..

More Information


  1. Deyde V, Sheu T, Trujillo A, Okomo Adhiambo M, Garten R, Klimov A, et al. Detection of molecular markers of drug resistance in 2009 pandemic influenza A (H1N1) viruses by pyrosequencing. Antimicrob Agents Chemother. 2010;54:1102-10 pubmed publisher
    ..Pyrosequencing is well suited for the detection of drug resistance markers and signature mutations in the M and NA gene segments of the pandemic H1N1 influenza viruses. ..
  2. Metzner K, Rauch P, von Wyl V, Leemann C, Grube C, Kuster H, et al. Efficient suppression of minority drug-resistant HIV type 1 (HIV-1) variants present at primary HIV-1 infection by ritonavir-boosted protease inhibitor-containing antiretroviral therapy. J Infect Dis. 2010;201:1063-71 pubmed publisher
    ..Under this high genetic resistance barrier regimen, the M184V was not further selected. ..
  3. Earhart K, Elsayed N, Saad M, Gubareva L, Nayel A, Deyde V, et al. Oseltamivir resistance mutation N294S in human influenza A(H5N1) virus in Egypt. J Infect Public Health. 2009;2:74-80 pubmed publisher
    ..To our knowledge, this is the first time oseltamivir resistance has been detected in A(H5N1) infecting a human prior to treatment. ..
  4. Gatell J. The use of integrase inhibitors in treatment-experienced patients. Eur J Med Res. 2009;14 Suppl 3:30-5 pubmed
    ..Most likely explanation was the presence of archived resistance mutationts to background therapy leading to a functional monotherapy with raltegravir. ..
  5. Speers D, Williams S, Pinder M, Moody H, Hurt A, Smith D. Oseltamivir-resistant pandemic (H1N1) 2009 influenza in a severely ill patient: the first Australian case. Med J Aust. 2010;192:166-8 pubmed
    ..He subsequently died of non-respiratory complications. This is the first case of oseltamivir-resistant pandemic (H1N1) 2009 in Australia and the first report of resistance in a solid organ transplant recipient. ..
  6. Zoulim F, Locarnini S. Hepatitis B virus resistance to nucleos(t)ide analogues. Gastroenterology. 2009;137:1593-608.e1-2 pubmed publisher
  7. Germanaud D, Derache A, Traore M, Madec Y, Toure S, Dicko F, et al. Level of viral load and antiretroviral resistance after 6 months of non-nucleoside reverse transcriptase inhibitor first-line treatment in HIV-1-infected children in Mali. J Antimicrob Chemother. 2010;65:118-24 pubmed publisher
    ..The low frequency of TAMs suggests that most NRTIs can be used in a second-line regimen after early failure. ..
  8. Vercauteren J, Wensing A, van de Vijver D, Albert J, Balotta C, Hamouda O, et al. Transmission of drug-resistant HIV-1 is stabilizing in Europe. J Infect Dis. 2009;200:1503-8 pubmed publisher
    ..02). We found that TDR appears to be stabilizing in Europe, consistent with recent reports of decreasing drug resistance and improved viral suppression in patients treated for HIV-1 infection. ..
  9. Tashiro M, McKimm Breschkin J, Saito T, Klimov A, Macken C, Zambon M, et al. Surveillance for neuraminidase-inhibitor-resistant influenza viruses in Japan, 1996-2007. Antivir Ther. 2009;14:751-61 pubmed publisher
    ..In particular, although oseltamivir-resistant A(H1N1) viruses with the H274Y mutation spread globally in 2007-2008, we found little evidence for increasing levels of resistant A(H1N1) variants in Japan in preceding years. ..
  10. Steain M, Dwyer D, Hurt A, Kol C, Saksena N, Cunningham A, et al. Detection of influenza A H1N1 and H3N2 mutations conferring resistance to oseltamivir using rolling circle amplification. Antiviral Res. 2009;84:242-8 pubmed publisher
    ..These results were further confirmed by neuraminidase region sequencing. In conclusion, RCA technology can provide rapid (<24 h), high-throughput diagnosis of OTV resistance mutations with a high specificity and sensitivity. ..
  11. Dapat C, Saito R, Kyaw Y, Naito M, Hasegawa G, Suzuki Y, et al. Epidemiology of human influenza A and B viruses in Myanmar from 2005 to 2007. Intervirology. 2009;52:310-20 pubmed publisher
    ..Continuous surveillance in tropical countries is important for elucidating the seasonality of influenza and determining the molecular characteristics of circulating strains. ..
  12. Invernizzi C, Coutsinos D, Oliveira M, Moisi D, Brenner B, Wainberg M. Signature nucleotide polymorphisms at positions 64 and 65 in reverse transcriptase favor the selection of the K65R resistance mutation in HIV-1 subtype C. J Infect Dis. 2009;200:1202-6 pubmed publisher
    ..This is the first demonstration of the significance of silent nucleotide polymorphisms in the development of drug resistance. ..
  13. Fransen S, Gupta S, Danovich R, Hazuda D, Miller M, Witmer M, et al. Loss of raltegravir susceptibility by human immunodeficiency virus type 1 is conferred via multiple nonoverlapping genetic pathways. J Virol. 2009;83:11440-6 pubmed publisher
    ..This study demonstrates distinct genetic pathways to resistance in subjects failing raltegravir regimens and defines the effects of primary and secondary resistance mutations on raltegravir susceptibility and replication capacity. ..
  14. Reshi P, Lone I. Human immunodeficiency virus and pregnancy. Arch Gynecol Obstet. 2010;281:781-92 pubmed publisher
    ..The mother-to-child transmission which was of major concern previously can now be significantly reduced by newer management strategies. This review stresses on the management of pregnancy in HIV. ..
  15. Waterer G, Hui D, Jenkins C. Public health management of pandemic (H1N1) 2009 infection in Australia: a failure!. Respirology. 2010;15:51-6 pubmed publisher
    ..In this paper, two senior academics discuss the management of pandemic (H1N1) 2009 infection in Australia from the public health perspective. ..
  16. Kim H, Park D, Park J, Cho Y, Sohn C, Jeon W, et al. Comparison between clevudine and entecavir treatment for antiviral-naïve patients with chronic hepatitis B. Liver Int. 2010;30:834-40 pubmed publisher
    ..There has been no study comparing the clinical efficacy of clevudine and entecavir in antiviral-naïve patients with chronic hepatitis B (CHB)...
  17. Sophan S, Meng C, Pean P, Harwell J, Hutton E, Trzmielina S, et al. Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART). Southeast Asian J Trop Med Public Health. 2010;41:126-37 pubmed
    ..The study results suggest that MDOT may be effective for HAART administration in limited-resource settings like Cambodia. ..
  18. Lihana R, Khamadi S, Lubano K, Mwangi J, Kinyua J, Okoth V, et al. Genetic characterization of HIV type 1 among patients with suspected immune reconstitution inflammatory syndrome after initiation of antiretroviral therapy in Kenya. AIDS Res Hum Retroviruses. 2010;26:833-8 pubmed publisher
    ..Drug resistance may not be the only cause of ART adverse events. HIV-1 characterization would be important before and during HIV therapy to avoid treatment failure. ..
  19. Fonteh P, Keter F, Meyer D. HIV therapeutic possibilities of gold compounds. Biometals. 2010;23:185-96 pubmed publisher
    ..In addition, reports exist on gold-based inhibitors of reverse transcriptase (RT), protease (PR) and viral entry of host cells. These and other characteristics of gold-based HIV drugs are reviewed here...
  20. Zaki M, Saudy N, El Diasty A. Study of nitric oxide in patients with chronic hepatitis C genotype 4: relationship to viremia and response to antiviral therapy. Immunol Invest. 2010;39:598-610 pubmed publisher
    ..Therefore, it may be an important factor for chronic hepatitis C, which suggests an additional therapeutic pathway of anti-oxidants in combination with the standard regimen for further study. ..
  21. Bihl F, Negro F. Treatment of chronic hepatitis C. Minerva Med. 2009;100:459-65 pubmed
    ..The advent of these drugs will further ameliorate response rates and facilitate the permanent cure of chronic hepatitis C. ..
  22. Diop Ndiaye H, Toure Kane C, Leye N, Ngom Gueye N, Montavon C, Peeters M, et al. Antiretroviral drug resistance mutations in antiretroviral-naive patients from Senegal. AIDS Res Hum Retroviruses. 2010;26:1133-8 pubmed publisher
    ..9% for protease inhibitors at the time of scaling up. The prevalence in untreated patients remains low and stable, below 5% after 10 years of ARV circulation...
  23. Kim J, Jung Y, Joo M, Kim J, Yim H, Park J, et al. Hepatitis B viral surface mutations in patients with adefovir resistant chronic hepatitis B with A181T/V polymerase mutations. J Korean Med Sci. 2010;25:257-64 pubmed publisher
    ..Although sW172stop and sL173F mutations were detected, reduced HBsAg titer was not observed. Further study of these mutations and their clinical implications are needed...
  24. Kiseleva I, Larionova N, Kuznetsov V, Rudenko L. Phenotypic characteristics of novel swine-origin influenza A/California/07/2009 (H1N1) virus. Influenza Other Respir Viruses. 2010;4:1-5 pubmed publisher
    ..This finding suggests that this virus might be a good wild type parental prototype for live vaccine for potential use for controlling pandemic influenza. ..
  25. Su H, Liu Y, Liu W, Zhong Y, Chen X, Wang C, et al. [Analysis and recombinant construction of HBV the reverse transcriptase gene with drug-resistant mutations from 40 patients with chronic hepatitis B]. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2009;23:340-2 pubmed
    ..The work lays a foundation for drug-resistant phenotypic analysis of HBV mutants. ..
  26. Wongprasit P, Manosuthi W, Kiertiburanakul S, Sungkanuparph S. Hepatitis B virus drug resistance in HIV-1-infected patients taking lamivudine-containing antiretroviral therapy. AIDS Patient Care STDS. 2010;24:205-9 pubmed publisher
    ..Positive HBeAg and longer duration of lamivudine use are risk factors for HBV-DR. In addition to lamivudine resistance, cross-resistance to other anti-HBV drugs is also frequently observed. ..
  27. Coutsinos D, Invernizzi C, Xu H, Brenner B, Wainberg M. Factors affecting template usage in the development of K65R resistance in subtype C variants of HIV type-1. Antivir Chem Chemother. 2010;20:117-31 pubmed publisher
    ..These results further establish a mechanistic basis for the exclusion of both K65R and TAMs on single templates as well as the preferential acquisition of K65R in subtype C viruses. ..
  28. Hare S, Vos A, Clayton R, Thuring J, Cummings M, Cherepanov P. Molecular mechanisms of retroviral integrase inhibition and the evolution of viral resistance. Proc Natl Acad Sci U S A. 2010;107:20057-62 pubmed publisher
    ..Furthermore, our structures predict physical proximity and an interaction between HIV-1 IN mutant residues His148 and Ser/Ala140, rationalizing the coevolution of Q148H and G140S/A mutations in drug-resistant viral strains...
  29. Tebit D, Lobritz M, Lalonde M, Immonen T, Singh K, SARAFIANOS S, et al. Divergent evolution in reverse transcriptase (RT) of HIV-1 group O and M lineages: impact on structure, fitness, and sensitivity to nonnucleoside RT inhibitors. J Virol. 2010;84:9817-30 pubmed publisher
  30. Métifiot M, Maddali K, Naumova A, Zhang X, Marchand C, Pommier Y. Biochemical and pharmacological analyses of HIV-1 integrase flexible loop mutants resistant to raltegravir. Biochemistry. 2010;49:3715-22 pubmed publisher
    ..Our results demonstrate that IN mutations at positions 140 and 148 in the IN flexible loop can account for the phenotype of RAL-resistant viruses. ..
  31. Chan P. Lancet conference: influenza in the Asia-Pacific and the international scientific symposium on influenza pandemic response and preparedness. Expert Rev Anti Infect Ther. 2009;7:1165-6 pubmed publisher
    ..Several highlights are described here. ..
  32. De Luca A, Prosperi M, Bracciale L. Resistance considerations in sequencing of antiretroviral therapy in low-middle income countries with currently available options. Curr Opin HIV AIDS. 2010;5:27-37 pubmed publisher
  33. Pielak R, Chou J. Solution NMR structure of the V27A drug resistant mutant of influenza A M2 channel. Biochem Biophys Res Commun. 2010;401:58-63 pubmed publisher
    ..The new structural data show that the amphipathic helices are packed much more closely to the channel domain and provide new insights into the proton transfer pathway. ..
  34. Abdool Karim Q, Abdool Karim S, Frohlich J, Grobler A, Baxter C, Mansoor L, et al. Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science. 2010;329:1168-74 pubmed publisher
    ..Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use. ..
  35. Squires K, Young B, DeJesus E, Bellos N, Murphy D, Sutherland Phillips D, et al. Safety and efficacy of a 36-week induction regimen of abacavir/lamivudine and ritonavir-boosted atazanavir in HIV-infected patients. HIV Clin Trials. 2010;11:69-79 pubmed publisher
    ..Few adverse events (3%) led to study discontinuation. Induction with ATV/RTV + ABC/3TC once daily provides an efficacious and well-tolerated regimen for the initial treatment of HIV. ..
  36. Shi B, Kitchen C, Weiser B, Mayers D, Foley B, Kemal K, et al. Evolution and recombination of genes encoding HIV-1 drug resistance and tropism during antiretroviral therapy. Virology. 2010;404:5-20 pubmed publisher
    ..Each patient displayed at least one recombinant encompassing env and representing a change in predicted tropism. These data suggest that, in addition to mutation, recombination can play a significant role in shaping HIV-1 evolution. ..
  37. Casalegno J, Bouscambert Duchamp M, Caro V, Schuffenecker I, Sabatier M, Traversier A, et al. Oseltamivir-resistant influenza A(H1N1) viruses in south of France, 2007/2009. Antiviral Res. 2010;87:242-8 pubmed
  38. Yuan Y, Cao X, Liu H, Xing H, Liu C, Cui W, et al. [Study on the transmission of drug resistant human immunodeficiency virus-1 in Henan province]. Zhonghua Yu Fang Yi Xue Za Zhi. 2009;43:956-9 pubmed
    ..However, the proportion of resistant strains would be higher with the antiretroviral treatment. We should pay more attention to the transmission of resistant strains and continue the drug resistance surveillance. ..
  39. Adiwijaya B, Herrmann E, Hare B, Kieffer T, Lin C, Kwong A, et al. A multi-variant, viral dynamic model of genotype 1 HCV to assess the in vivo evolution of protease-inhibitor resistant variants. PLoS Comput Biol. 2010;6:e1000745 pubmed publisher
    ..The modeling fitness estimates were robust in sensitivity analyses in which the restoration dynamics of replication space and assumptions of HCV mutation rates were varied. ..
  40. Doerig C, Antonino A, Pache I, Moradpour D. [Management of chronic hepatitis B]. Rev Med Suisse. 2010;6:168-70, 172-3 pubmed
    ..The purpose of this review is to provide a concise overview of the diagnosis and management of chronic hepatitis B. ..
  41. Ghosh G, Nakada N, Yamashita N, Tanaka H. Oseltamivir carboxylate, the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan. Environ Health Perspect. 2010;118:103-7 pubmed publisher
    ..OC is present in STP effluent and river water only during the flu season. Ozonation as tertiary treatment in STP will substantially reduce the OC load in STP effluent during an influenza epidemic or pandemic. ..
  42. Mochalova L, Bright R, Xu X, Korchagina E, Chinarev A, Bovin N, et al. Shift in oligosaccharide specificities of hemagglutinin and neuraminidase of influenza B viruses resistant to neuraminidase inhibitors. Glycoconj J. 2010;27:321-7 pubmed publisher
    ..Thus, the development of the NAI resistance in the studied influenza B viruses was accompanied by a readjustment of HA-NA oligosaccharide specificities. ..
  43. van Marle G, Church D, Nunweiler K, Cannon K, Wainberg M, Gill M. Higher levels of Zidovudine resistant HIV in the colon compared to blood and other gastrointestinal compartments in HIV infection. Retrovirology. 2010;7:74 pubmed publisher
    ..This study confirms that different drug-resistant HIV-1 variants are present in different gut tissues, and it is the first report to document that particular gut tissues may select for drug resistant HIV-1 variants. ..
  44. Bandaranayake R, Kolli M, King N, Nalivaika E, Heroux A, Kakizawa J, et al. The effect of clade-specific sequence polymorphisms on HIV-1 protease activity and inhibitor resistance pathways. J Virol. 2010;84:9995-10003 pubmed publisher
    ..In combination, our studies show that sequence polymorphisms within clades can alter protease activity and inhibitor binding and are capable of altering the pathway to inhibitor resistance. ..
  45. Bansi L, Geretti A, Dunn D, Hill T, Green H, Fearnhill E, et al. Impact of transmitted drug-resistance on treatment selection and outcome of first-line Highly Active Antiretroviral Therapy (HAART). J Acquir Immune Defic Syndr. 2010;53:633-9 pubmed
    ..PI/r-based therapy was often selected in patients with resistance to the nucleoside reverse transcriptase inhibitor backbone. Low GSS predicted poor virological suppression and the association persisted after adjusting for PI/r use. ..
  46. Lacombe K, Boyd A, Gozlan J, Lavocat F, Girard P, Zoulim F. Drug-resistant and immune-escape HBV mutants in HIV-infected hosts. Antivir Ther. 2010;15:493-7 pubmed publisher
    ..For patients coinfected with HIV, hepatitis B treatment options that aim to reduce the risk of HBV mutations from emerging must be seriously considered, not only from clinical but also public health perspectives. ..
  47. Xu G, You Q, Pickerill S, Zhong H, Wang H, Shi J, et al. Application of PCR-LDR-nucleic acid detection strip in detection of YMDD mutation in hepatitis B patients treated with lamivudine. J Med Virol. 2010;82:1143-9 pubmed publisher
    ..This warrants its further development and suggests that the PLNA method could be a useful tool in detecting LAM resistance. ..
  48. Strasfeld L, Chou S. Antiviral drug resistance: mechanisms and clinical implications. Infect Dis Clin North Am. 2010;24:413-37 pubmed publisher
    ..This article discusses drug resistance in herpesviruses and hepatitis B. ..
  49. Peres da Silva A, de Almeida A, Lampe E. Mutations in hepatitis C virus NS3 protease domain associated with resistance to specific protease inhibitors in antiviral therapy naïve patients. Arch Virol. 2010;155:807-11 pubmed publisher
    ..1% of isolates of subtype 1a. In conclusion, the presence of variants carrying mutations associated with resistance to protease inhibitors in therapy-naïve patients may be important for future therapeutic strategies. ..
  50. Elsayed R, Caldwell D. Etravirine: A novel nonnucleoside reverse transcriptase inhibitor for managing human immunodeficiency virus infection. Am J Health Syst Pharm. 2010;67:193-205 pubmed publisher
    ..Etravirine, a second-generation NNRTI, is efficacious in achieving viral suppression and improving the immune function in treatment-experienced HIV-infected patients. ..
  51. Asmuth D, Goodrich J, Cooper D, Haubrich R, Rajicic N, Hirschel B, et al. CD4+ T-cell restoration after 48 weeks in the maraviroc treatment-experienced trials MOTIVATE 1 and 2. J Acquir Immune Defic Syndr. 2010;54:394-7 pubmed publisher
    ..This additional CD4 response was associated with a longer time to the development of AIDS-defining events on MVC. ..
  52. Weisser H, Altmann A, Sierra S, Incardona F, Struck D, Sonnerborg A, et al. Only slight impact of predicted replicative capacity for therapy response prediction. PLoS ONE. 2010;5:e9044 pubmed publisher
    ..However, the observed improvement could simply be a consequence of the significant correlation between pRC and drug resistance. ..
  53. Baranovich T, Saito R, Suzuki Y, Zaraket H, Dapat C, Caperig Dapat I, et al. Emergence of H274Y oseltamivir-resistant A(H1N1) influenza viruses in Japan during the 2008-2009 season. J Clin Virol. 2010;47:23-8 pubmed publisher
    ..Intensified surveillance, including phenotypic assays and sequencing of the hemagglutinin, neuraminidase, and M2 gene would allow monitoring of the spread and evolution of drug-resistant influenza virus variants. ..