Skip to main content

Advertisement

SpringerLink
Log in

Antiretroviral drug resistance in HIV-1

  • Published:
Current Infectious Disease Reports Aims and scope Submit manuscript

Abstract

Progress in understanding antiretroviral resistance has evolved rapidly in recent years. Specific resistance mutations have been associated with virologic failure of different nucleoside reverse transcriptase inhibitors (NRTIs). These mutations vary in the extent of cross resistance they confer to other drugs in the same class. In addition, two novel mutational patterns conferring resistance to multiple NRTIs have been recognized. Considerable class specific cross resistance also exists among viruses with reduced susceptibility to nonnucleoside reverse transcriptase inhibitors (NNRTIs). Among protease inhibitors, low level resistance that arises early during virologic failure may be drug specific in some situations, but high level resistance seen later during suboptimal therapy is likely t confer cross resistance to the entire class. Prevalence of drug resistance in infected patients appears to be considerable, and transmission of multidrug-resistant virus has been documented. Current methods of testing for resistance are promising, but they have significant limitations and require further clinical validation. The best approach to prevent resistance is to start treatment early during infection with a regimen that engenders good compliance and is potent enough to decrease viral load to below detection limits of the most sensitive assay available. Once resistance arises, salvage regimens in general have compromised efficacy and should be planned with attention t the patient’s prior drug treatment history and the viruses’ suspected or demonstrated resistance patterns.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Larder BA, Darby G, Richman DD: HIV with reduced sensitivity to zidovudine (AZT) isolated during prolonged therapy. Science 1989, 243:1731–1734.

    Article  PubMed  CAS  Google Scholar 

  2. Coffin JM: HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 1995, 267:483–489.

    Article  PubMed  CAS  Google Scholar 

  3. Loveday C, Kaye S, Tenant-Flowers M, et al.: HIV-1 RNA serumload and resistant viral genotypes during early zidovudine therapy. Lancet 1995, 345:820–824.

    Article  PubMed  CAS  Google Scholar 

  4. Boucher CA, O’Sullivan E, Mulder JW, et al.: Ordered appearance of zidovudine resistance mutations during treatment of 18 human immunodeficiency virus-positive subjects. J Infect Dis 1992, 165:105–110.

    PubMed  CAS  Google Scholar 

  5. Hooker DJ, Tachedjian G, Solomon AE, et al.: An in vivo mutation from leucine to tryptophan at position 210 in human immunodeficiency virus type 1 reverse transcriptase contributes to high-level resistance to 3‘-azido-3’-deoxythymidine. J Virol 1996, 70:8010–8018.

    PubMed  CAS  Google Scholar 

  6. Larder BA, Kellam P, Kemp SD: Zidovudine resistance predicted by direct detection of mutations in DNA from HIV-infected lymphocytes. AIDS 1991, 5:137–144.

    Article  PubMed  CAS  Google Scholar 

  7. Harrigan PR, Kinghorn I, Bloor S, et al.: Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility. J Virol 1996, 70:5930–5934.

    PubMed  CAS  Google Scholar 

  8. Chow YK, Hirsch MS, Merrill DP, et al.: Use of evolutionary limitations of HIV-1 multidrug resistance to optimize therapy. Nature 1993, 361:650–654.

    Article  PubMed  CAS  Google Scholar 

  9. Harrigan PR, Bloor S, Larder BA: Relative replicative fitness of zidovudine-resistant human immunodeficiency virus type 1 isolates in vitro. J Virol 1998, 72:3773–3778.

    PubMed  CAS  Google Scholar 

  10. Caliendo AM, Savara A, An D, et al.: Effects of zidovudineselected human immunodeficiency virus type 1 reverse transcriptase amino acid substitutions on processive DNA synthesis and viral replication. J Virol 1996, 70:2146–2153.

    PubMed  CAS  Google Scholar 

  11. Arion D, Kaushik N, McCormick S, et al.: Phenotypic mechanism of HIV-1 resistance to 3‘-azido-3’-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase. Biochemistry 1998, 37:15908–15917.

    Article  PubMed  CAS  Google Scholar 

  12. D’Aquila RT, Johnson VA, Welles SL, et al.: Zidovudine resistance and HIV-1 disease progression during antiretroviral therapy. AIDS Clinical Trials Group Protocol 116B/117 Team and the Virology Committee Resistance Working Group. Ann Intern Med 1995, 122:401–408.

    PubMed  CAS  Google Scholar 

  13. Mayers DL, Japour AJ, Arduino JM, et al.: Dideoxynucleoside resistance emerges with prolonged zidovudine monotherapy. The RV43 Study Group. Antimicrob Agents Chemother 1994, 38:307–314.

    PubMed  CAS  Google Scholar 

  14. Larder B: New insights into genetic mechanisms of HIV drug resistance [abstract S34]. In 6th Conference on Retroviruses and Opportunistic Infections Chicago, 1999:218.

  15. St Clair MH, Martin JL, Tudor-Williams G, et al.: Resistance to ddI and sensitivity to AZT induced by a mutation in HIV-1 reverse transcriptase. Science 1991, 253:1557–1559.

    Article  PubMed  CAS  Google Scholar 

  16. Eron JJ, Chow YK, Caliendo AM, et al.: pol Mutations conferring zidovudine and didanosine resistance with different effects in vitro yield multiply resistant human immunodeficiency virus type 1 isolates in vivo. Antimicrob Agents Chemother 1993, 37:1480–1487.

    PubMed  CAS  Google Scholar 

  17. Gu Z, Gao Q, Li X, et al.: Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2‘,3’-dideoxyinosine and 2‘,3’-dideoxycytidine. J Virol 1992, 66:7128–7135.

    PubMed  CAS  Google Scholar 

  18. Zhang D, Caliendo AM, Eron JJ, et al.: Resistance to 2‘,3’-dideoxycytidine conferred by a mutation in codon 65 of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1994, 38:282–287.

    PubMed  CAS  Google Scholar 

  19. Fitzgibbon JE, Howell RM, Haberzettl CA, et al.: Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2‘,3’-dideoxycytidine. Antimicrob Agents Chemother 1992, 36:153–157.

    PubMed  CAS  Google Scholar 

  20. Kozal MJ, Kroodsma K, Winters MA, et al.: Didanosine resistance in HIV-infected patients switched from zidovudine to didanosine monotherapy. Ann Intern Med 1994, 121:263–268.

    PubMed  CAS  Google Scholar 

  21. Winters MA, Shafer RW, Jellinger RA, et al.: Human immunodeficiency virus type 1 reverse transcriptase genotype and drug susceptibility changes in infected individuals receiving dideoxyinosine monotherapy for 1 to 2 years. Antimicrob Agents Chemother 1997, 41:757–762.

    PubMed  CAS  Google Scholar 

  22. Sharma PL, Crumpacker CS: Attenuated replication of human immunodeficiency virus type 1 with a didanosine-selected reverse transcriptase mutation. J Virol 1997, 71:8846–8851.

    PubMed  CAS  Google Scholar 

  23. Shafer RW, Kozal MJ, Winters MA, et al.: Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations. J Infect Dis 1994, 169:722–729.

    PubMed  CAS  Google Scholar 

  24. Shafer RW, Iversen AK, Winters MA, et al.: Drug resistance and heterogeneous long-term virologic responses of human immunodeficiency virus type 1-infected subjects to zidovudine and didanosine combination therapy. The AIDS Clinical Trials Group 143 Virology Team. J Infect Dis 1995, 172:70–78.

    PubMed  CAS  Google Scholar 

  25. Larder BA, Kohli A, Bloor S, et al.: Human immunodeficiency virus type 1 drug susceptibility during zidovudine (AZT) monotherapy compared with AZT plus 2′,3′-dideoxyinosine or AZT plus 2‘,3’-dideoxycytidine combination therapy. The protocol 34,225-02 Collaborative Group. J Virol 1996, 70:5922–5929.

    PubMed  CAS  Google Scholar 

  26. Lacey SF, Larder BA: Novel mutation (V75T) in human immunodeficiency virus type 1 reverse transcriptase confers resistance to 2‘,3’-didehydro-2‘,3’-dideoxythymidine in cell culture. Antimicrob Agents Chemother 1994, 38:1428–1432.

    PubMed  CAS  Google Scholar 

  27. Lin PF, Samanta H, Rose RE, et al.: Genotypic and phenotypic analysis of human immunodeficiency virus type 1 isolates from patients on prolonged stavudine therapy. J Infect Dis 1994, 170:1157–1164.

    PubMed  CAS  Google Scholar 

  28. Soriano V, Dietrich U, Villalba N, et al.: Lack of emergence of genotypic resistance to stavudine after 2 years of monotherapy. AIDS 1997, 11:696–697.

    PubMed  CAS  Google Scholar 

  29. Coakley E, Gillis J, Hammer S: Mutations in the reverse transcriptase genome of HIV-1 isolates derived from subjects treated with didanosine and stavudine in combination [abstract no 116]. In 6th Conference on Retroviruses and Opportunistic Infections Chicago, 1999:89.

  30. Tisdale M, Kemp SD, Parry NR, et al.: Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3’-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. Proc Natl Acad Sci U S A 1993, 90:5653–5656.

    Article  PubMed  CAS  Google Scholar 

  31. Schuurman R, Nijhuis M, van Leeuwen R, et al.: Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC). J Infect Dis 1995, 171:1411–1419.

    PubMed  CAS  Google Scholar 

  32. Larder BA, Kemp SD, Harrigan PR: Potential mechanism for sustained antiretroviral efficacy of AZT-3TC combination therapy. Science 1995, 269:696–699.

    Article  PubMed  CAS  Google Scholar 

  33. Katlama C, Ingrand D, Loveday C, et al.: Safety and efficacy of lamivudine-zidovudine combination therapy in antiretroviral-naive patients. A randomized controlled comparison with zidovudine monotherapy. Lamivudine European HIV Working Group. JAMA 1996, 276:118–125.

    Article  PubMed  CAS  Google Scholar 

  34. Miller V, Phillips A, Rottmann C, et al.: Dual resistance to zidovudine and lamivudine in patients treated with zidovudine-lamivudine combination therapy: association with therapy failure. J Infect Dis 1998, 177:1521–1532.

    PubMed  CAS  Google Scholar 

  35. Nijhuis M, Schuurman R, de Jong D, et al.: Lamivudine-resistant human immunodeficiency virus type 1 variants (184V) require multiple amino acid changes to become co-resistant to zidovudine in vivo. J Infect Dis 1997, 176:398–405.

    PubMed  CAS  Google Scholar 

  36. Kemp SD, Shi C, Bloor S, et al.: A novel polymorphism at codon 333 of human immunodeficiency virus type 1 reverse transcriptase can facilitate dual resistance to zidovudine and L-2‘,3’-dideoxy-3’-thiacytidine. J Virol 1998, 72:5093–5098.

    PubMed  CAS  Google Scholar 

  37. Miller V, Sturmer M, Staszewski S, et al.: The M184V mutation in HIV-1 reverse transcriptase (RT) conferring lamivudine resistance does not result in broad cross-resistance to nucleoside analogue RT inhibitors. AIDS 1998, 12:705–712.

    Article  PubMed  CAS  Google Scholar 

  38. Tisdale M, Alnadaf T, Cousens D: Combination of mutations in human immunodeficiency virus type 1 reverse transcriptase required for resistance to the carbocyclic nucleoside 1592U89. Antimicrob Agents Chemother 1997, 41:1094–1098.

    PubMed  CAS  Google Scholar 

  39. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services and Henry J Kaiser Family Foundation. MMWR 1998, 47:43–82. These are comprehensive consensus guidelines on treatment of HIV-1 infection in adults. The guidelines cover properties of different available drugs, treatment of antiretroviral-naive patients, and treatment issues in drug-experienced patients with virologic failure.

  40. Carpenter CC, Fischl MA, Hammer SM, et al.: Antiretroviral therapy for HIV infection in 1998: updated recommendations of the International AIDS Society-USA Panel. JAMA 1998, 280:78–86. These are consensus recommendations for HIV treatment strategies that are very similar to those in the preceding reference.

    Article  PubMed  CAS  Google Scholar 

  41. 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.

    Article  PubMed  CAS  Google Scholar 

  42. Kavlick MF, Wyvill K, Yarchoan R, et al.: Emergence of multidideoxynucleoside-resistant human immunodeficiency virus type 1 variants, viral sequence variation, and disease progression in patients receiving antiretroviral chemotherapy. J Infect Dis 1998, 177:1506–1513.

    PubMed  CAS  Google Scholar 

  43. Maeda Y, Venzon DJ, Mitsuya H: Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance. J Infect Dis 1998, 177:1207–1213.

    PubMed  CAS  Google Scholar 

  44. De Antoni A, Foli A, Lisziewicz J, et al.: Mutations in the pol gene of human immunodeficiency virus type 1 in infected patients receiving didanosine and hydroxyurea combination therapy. J Infect Dis 1997, 176:899–903.

    PubMed  CAS  Google Scholar 

  45. Winters MA, Coolley KL, Girard YA, et al.: A 6-basepair insert in the reverse transcriptase gene of human immunodeficiency virus type 1 confers resistance to multiple nucleoside inhibitors. J Clin Invest 1998, 102:1769–1775.

    PubMed  CAS  Google Scholar 

  46. de Jong JJ, Goudsmit J, Lukashov VV, et al.: Insertion of two amino acids combined with changes in reverse transcriptase containing tyrosine-215 of HIV-1 resistant to multiple nucleoside analogs. AIDS 1999, 13:75–80.

    Article  PubMed  Google Scholar 

  47. Mulato AS, Lamy PD, Miller MD, et al.: Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from AIDS patients after prolonger adefovir dipivoxil therapy. Antimicrob Agents Chemother 1998, 42:1620–1628.

    PubMed  CAS  Google Scholar 

  48. Miller MD, Anton KE, Mulato AS, et al.: Human immunodeficiency virus type 1 expressing the lamivudine-associated M184V mutation in reverse transcriptase shows increased susceptibility to adefovir and decreased replication capability in vitro. J Infect Dis 1999, 179:92–100.

    Article  PubMed  CAS  Google Scholar 

  49. Cherrington JM, Mulato AS, Lamy PD, et al.: Adefovir dipivoxil (bis-POM PMEA) therapy significantly decreases HIV RNA in patients with high-level zidovudine/lamivudineresistant HIV [abstract 4]. In 2nd International Workshop on HIV Drug Resistance and Treatment Strategies. Lake Maggiore, Italy, 1998:4–5.

    Google Scholar 

  50. Srinivas RV, Fridland A: Antiviral activities of 9-R-2-phosphonomethoxypropyl adenine (PMPA) and bis(isopropyloxymethylcarbonyl) PMPA against various drug-resistant human immunodeficiency virus strains. Antimicrob Agents Chemother 1998, 42:1484–1487.

    PubMed  CAS  Google Scholar 

  51. Byrnes VW, Sardana VV, Schleif WA, et al.: Comprehensive mutant enzyme and viral variant assessment of human immunodeficiency virus type 1 reverse transcriptase resistance to nonnucleoside inhibitors. Antimicrob Agents Chemother 1993, 37:1576–1579.

    PubMed  CAS  Google Scholar 

  52. Havlir D, McLaughlin MM, Richman DD: A pilot study to evaluate the development of resistance to nevirapine in asymptomatic human immunodeficiency virus-infected patients with CD4 cell counts of > 500/mm3: AIDS Clinical Trials Group Protocol 208. J Infect Dis 1995, 172:1379–1383.

    PubMed  CAS  Google Scholar 

  53. de Jong MD, Vella S, Carr A, et al.: High-dose nevirapine in previously untreated human immunodeficiency virus type 1-infected persons does not result in sustained suppression of viral replication. J Infect Dis 1997, 175:966–970.

    Article  PubMed  Google Scholar 

  54. Larder BA: 3‘-Azido-3’-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. Antimicrob Agents Chemother 1992, 36:2664–2669.

    PubMed  CAS  Google Scholar 

  55. Richman DD, Havlir D, Corbeil J, et al.: Nevirapine resistance mutations of human immunodeficiency virus type 1 selected during therapy. J Virol 1994, 68:1660–1666.

    PubMed  CAS  Google Scholar 

  56. Demeter LM, Meehan PM, Morse G, et al.: HIV-1 drug susceptibilities and reverse transcriptase mutations in patients receiving combination therapy with didanosine and delavirdine. J Acquir Immune Defic Syndr Hum Retrovir 1997, 14:136–144.

    CAS  Google Scholar 

  57. Young SD, Britcher SF, Tran LO, et al.: L-743, 726 (DMP-266): a novel, highly potent nonnucleoside inhibitor of the human immunodeficiency virus type 1 reverse transcriptase. Antimicrob Agents Chemother 1995, 39:2602–2605.

    PubMed  CAS  Google Scholar 

  58. Bacheler L, Weislow O, Snyder S, et al.: Virologic resistance to efavirenz [abstract no 41213]. In 12th International Conference on AIDS. Geneva, 1998:784.

  59. Fujiwara T, Sato A, el-Farrash M, et al.: S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1. Antimicrob Agents Chemother 1998, 42:1340–1345.

    PubMed  CAS  Google Scholar 

  60. Croteau G, Doyon L, Thibeault D, et al.: Impaired fitness of human immunodeficiency virus type 1 variants with high-level resistance to protease inhibitors. J Virol 1997, 71:1089–1096.

    PubMed  CAS  Google Scholar 

  61. Zennou V, Mammano F, Paulous S, et al.: Loss of viral fitness associated with multiple Gag and Gag-Pol processing defects in human immunodeficiency virus type 1 variants selected for resistance to protease inhibitors in vivo. J Virol 1998, 72:3300–3306.

    PubMed  CAS  Google Scholar 

  62. Martinez-Picado J, Savara AV, Sutton L, et al.: Replicative fitness of protease inhibitor resistant mutants of human immunodeficiency virus type 1. J Virol 1999, 73:3744–3752.

    PubMed  CAS  Google Scholar 

  63. Doyon L, Croteau G, Thibeault D, et al.: Second locus involved in human immunodeficiency virus type 1 resistance to protease inhibitors. J Virol 1996, 70:3763–3769.

    PubMed  CAS  Google Scholar 

  64. Zhang YM, Imamichi H, Imamichi T, et al.: Drug resistance during indinavir therapy is caused by mutations in the protease gene and in its Gag substrate cleavage sites. J Virol 1997, 71:6662–6670.

    PubMed  CAS  Google Scholar 

  65. Eberle J, Bechowsky B, Rose D, et al.: Resistance of HIV type 1 to proteinase inhibitor Ro 31-8959. AIDS Res Hum Retrovir 1995, 11:671–676.

    PubMed  CAS  Google Scholar 

  66. Jacobsen H, Hanggi M, Ott M, et al.: In vivo resistance to a human immunodeficiency virus type 1 proteinase inhibitor: mutations, kinetics, and frequencies. J Infect Dis 1996, 173:1379–1387.

    PubMed  CAS  Google Scholar 

  67. Markowitz M, Mo H, Kempf DJ, et al.: Selection and analysis of human immunodeficiency virus type 1 variants with increased resistance to ABT-538, a novel protease inhibitor. J Virol 1995, 69:701–706.

    PubMed  CAS  Google Scholar 

  68. Molla A, Korneyeva M, Gao Q, et al.: Ordered accumulation of mutations in HIV protease confers resistance to ritonavir. Nat Med 1996, 2:760–766.

    Article  PubMed  CAS  Google Scholar 

  69. Nijhuis M, Boucher CA, Schipper P, et al.: Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy. Proc Natl Acad Sci U S A 1998, 95:14441–14446.

    Article  PubMed  CAS  Google Scholar 

  70. Condra JH, Schleif WA, Blahy OM, et al.: In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995, 374:569–571.

    Article  PubMed  CAS  Google Scholar 

  71. Condra JH, Holder DJ, Schleif WA, et al.: Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. J Virol 1996, 70:8270–8276.

    PubMed  CAS  Google Scholar 

  72. Ruiz L, Nijhuis M, Boucher C, et al.: Efficacy of adding indinavir to previous reverse transcriptase nucleoside analogues in relation to genotypic and phenotypic resistance development in advanced HIV-1-infected patients. J Acquir Immune Defic Syndr Hum Retrovir 1998, 19:19–28.

    CAS  Google Scholar 

  73. Patick AK, Duran M, Cao Y, et al.: Genotypic and phenotypic characterization of human immunodeficiency virus type 1 variants isolated from patients treated with the protease inhibitor nelfinavir. Antimicrob Agents Chemother 1998, 42:2637–2644.

    PubMed  CAS  Google Scholar 

  74. Partaledis JA, Yamaguchi K, Tisdale M, et al.: In vitro selection and characterization of human immunodeficiency virus type 1 (HIV-1) isolates with reduced sensitivity to hydroxyethylamino sulfonamide inhibitors of HIV-1 aspartyl protease. J Virol 1995, 69:5228–5235.

    PubMed  CAS  Google Scholar 

  75. De Pasquale MP, Murphy R, Gulick R, et al.: Mutations selected in HIV plasma RNA during 141W94 therapy [abstract 406a]. In 5th Conference on Retroviruses and Opportunistic Infections. Chicago, 1998:155.

  76. Carrillo A, Stewart KD, Sham HL, et al.: In vitro selection and characterization of human immunodeficiency virus type 1 variants with increased resistance to ABT-378, a novel protease inhibitor. J Virol 1998, 72:7532–7541.

    PubMed  CAS  Google Scholar 

  77. Lorenzi P, Oprival M, Hirschel B, et al.: Impact of drug resistance mutations on virologic response to salvage therapy. AIDS 1999, 13:F17-F21.

    Article  PubMed  CAS  Google Scholar 

  78. Gomez-Cano M, Rubio A, Puig T, et al.: Prevalence of genotypic resistance to nucleoside analogues in antiretroviralnaive and antiretroviral-experienced HIV-infected patients in Spain. AIDS 1998, 12:1015–1020.

    Article  PubMed  CAS  Google Scholar 

  79. Shafer RW, Winters MA, Palmer S, et al.: Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients. Ann Intern Med 1998, 128:906–911.

    PubMed  CAS  Google Scholar 

  80. Kully C, Yerly S, Erb P, et al.: Codon 215 mutations in human immunodeficiency virus-infected pregnant women. The Swiss Collaborative “HIV and Pregnancy” Study. J Infect Dis 1999, 179:705–708.

    Article  PubMed  CAS  Google Scholar 

  81. Imrie A, Beveridge A, Genn W, et al.: Transmission of human immunodeficiency virus type 1 resistant to nevirapine and zidovudine. Sydney Primary HIV Infection Study Group. J Infect Dis 1997, 175:1502–1506.

    PubMed  CAS  Google Scholar 

  82. Hecht FM, Grant RM, Petropoulos CJ, et al.: Sexual transmission of an HIV-1 variant resistant to multiple reverse-transcriptase and protease inhibitors. N Engl J Med 1998, 339:307–311. This report is the first to demonstrate transmission of virus resistant to both RT inhibitors and protease inhibitors. It also contains a description of a clinically applicable method for virus phenotypic susceptibility.

    Article  PubMed  CAS  Google Scholar 

  83. Colgrove RC, Pitt J, Chung PH, et al.: Selective vertical transmission of HIV-1 antiretroviral resistance mutations. AIDS 1998, 12:2281–2288.

    Article  PubMed  CAS  Google Scholar 

  84. Hirsch MS, Conway B, D’Aquila RT, et al.: Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society--USA Panel. JAMA 1998, 279:1984–1991. This paper is a consensus statement on clinical issues related to antiretroviral resistance. It includes information on resistance genotypes, techniques of genotypic and phenotypic resistance determination, and recommendations for clinical management.

    Article  PubMed  CAS  Google Scholar 

  85. Kozal MJ, Shah N, Shen N, et al.: Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat Med 1996, 2:753–759.

    Article  PubMed  CAS  Google Scholar 

  86. Gunthard HF, Wong JK, Ignacio CC, et al.: Comparative performance of high-density oligonucleotide sequencing and dideoxynucleotide sequencing of HIV type 1 pol from clinical samples. AIDS Res Hum Retrovir 1998, 14:869–876.

    Article  PubMed  CAS  Google Scholar 

  87. Stuyver L, Wyseur A, Rombout A, et al.: Line probe assay for rapid detection of drug-selected mutations in the human immunodeficiency virus type 1 reverse transcriptase gene. Antimicrob Agents Chemother 1997, 41:284–291.

    PubMed  CAS  Google Scholar 

  88. Hertogs K, de Bethune MP, Miller V, et al.: A rapid method for simultaneous detection of phenotypic resistance to inhibitors of protease and reverse transcriptase in recombinant human immunodeficiency virus type 1 isolates from patients treated with antiretroviral drugs. Antimicrob Agents Chemother 1998, 42:269–276. This is a description of a clinically applicable method for virus susceptibility phenotyping.

    Article  PubMed  CAS  Google Scholar 

  89. Baxter JD, Mayers DL, Wentworth DN, et al.: A pilot study of the short-term effects of antiretroviral management on plasma genotypic antiretroviral resistance testing (GART) in patients failing antiretroviral therapy [abstract LB8]. In 6th Conference on Retroviruses and Opportunistic Infections. Chicago, 1999:206.

  90. Fatkenheuer G, Theisen A, Rockstroh J, et al.: Virological treatment failure of protease inhibitor therapy in an unselected cohort of HIV-infected patients. AIDS 1997, 11:F113-F116.

    Article  PubMed  CAS  Google Scholar 

  91. Raboud JM, Montaner JS, Conway B, et al.: Suppression of plasma viral load below 20 copies/ml is required to achieve a long-term response to therapy. AIDS 1998, 12:1619–1624.

    Article  PubMed  CAS  Google Scholar 

  92. Vanhove GF, Schapiro JM, Winters MA, et al.: Patient compliance and drug failure in protease inhibitor monotherapy. JAMA 1996, 276:1955–1956.

    Article  PubMed  CAS  Google Scholar 

  93. Davey RT, Jr, Chaitt DG, Reed GF, et al.: Randomized, controlled phase I/II, trial of combination therapy with delavirdine (U-90152S) and conventional nucleosides in human immunodeficiency virus type 1-infected patients. Antimicrob Agents Chemother 1996, 40:1657–1664.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Infectious Disease Unit and AIDS Research Center, Massachusetts General Hospital, 149 13th Street, 02129, Charlestown, MA, USA

    George J. Hanna MD & Richard T. D’Aquila MD

Authors
  1. George J. Hanna MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard T. D’Aquila MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hanna, G.J., D’Aquila, R.T. Antiretroviral drug resistance in HIV-1. Curr Infect Dis Rep 1, 289–297 (1999). https://doi.org/10.1007/s11908-999-0032-4

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11908-999-0032-4

Keywords

Search

Navigation