1887

Abstract

The impact of emergence of genetic resistance, soon after the beginning of antiretroviral therapy, on the genotype of other viral loci not implicated in the development of resistance was studied in four human immunodeficiency type 1 (HIV-1)-infected patients subjected to indinavir monotherapy. Two patients were chosen because they showed no decrease in virus load during the study period and two were selected because they showed a rapid decline in plasma viraemia after the initiation of therapy and a virus rebound after 12 weeks of treatment. The evolution of virus sequences was analysed within the four infected patients by examining virus sequences spanning the protease and C2–V3 genes by RT–PCR of plasma samples obtained at the beginning and after 12 weeks of therapy. PCR products from the two genomic regions from the two sample points per patient were cloned and 10–15 clones from each sample were sequenced. Genotypic indinavir resistance was present in the four patients after 12 weeks of therapy. The overall protease and C2–V3 regions quasispecies diversity at time zero was higher than that after 12 weeks of therapy, but this difference was more significant in the two patients who showed a reduction in virus load soon after the initiation of treatment. C2–V3 sequences indicated that changes during emergence of resistance to indinavir were only detected in the two patients who showed a drastic reduction in virus load. Thus, a temporal relationship was observed between the start of therapy, a drastic reduction in virus load and a drift in the HIV-1 quasispecies.

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2000-01-01
2024-11-12
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References

  1. Blaak, H., Brouwer, M., Ran, L. J., de Wolf, F. & Schuitemaker, H.(1998). In vitro replication kinetics of human immunodeficiency virus type 1 (HIV-1) variants in relation to virus load in long-term survivors of HIV-1 infection. Journal of Infectious Diseases 177, 600-610.[CrossRef] [Google Scholar]
  2. Boden, D. & Markowitz, M.(1998). Resistance to human immunodeficiency virus type 1 protease inhibitors. Antimicrobial Agents and Chemotherapy 42, 2775-2783. [Google Scholar]
  3. Boom, R., Sol, C. J. A., Salimans, M. M. M., Jansen, C. L., Wertheim-van Dillen, P. M. E. & van der Noordaa, J.(1990). Rapid and simple method for purification of nucleic acids. Journal of Clinical Microbiology 28, 495-503. [Google Scholar]
  4. Cabana, C., Clotet, B. & Martı́nez, M.-A. (1999). Emergence and genetic evolution of HIV-1 variants with mutations conferring resistance to multiple reverse transcriptase and protease inhibitors. Journal of Medical Virology 59, 480–490.[CrossRef] [Google Scholar]
  5. Chao, L.(1990). Fitness of RNA virus decreased by Muller’s ratchet. Nature 348, 454-455.[CrossRef] [Google Scholar]
  6. Cheynier, R., Henrichwark, S., Hadida, F., Pelletier, E., Oksenhendler, E., Autran, B. & Wain-Hobson, S.(1994). HIV and T cell expansion in splenic white pulps is accompanied by infiltration of HIV-specific cytotoxic T lymphocytes. Cell 78, 373-387.[CrossRef] [Google Scholar]
  7. Cheynier, R., Gratton, S., Halloran, M., Stahmer, I., Letvin, N. L. & Wain-Hobson, S. (1998). Antigenic stimulation by BCG vaccine as an in vivo driving force for SIV replication and dissemination. Nature Medicine 4, 421-427.[CrossRef] [Google Scholar]
  8. Clarke, D. K., Duarte, E. A., Moya, A., Elena, S. F., Domingo, E. & Holland, J. J. (1993). Genetic bottlenecks and population passages cause profound fitness differences in RNA viruses. Journal of Virology 67, 222-228. [Google Scholar]
  9. Cleland, A., Watson, H. G., Robertson, P., Ludlam, C. A. & Leigh-Brown, A. (1996). Evolution of zidovudine resistance-associated genotypes in human immunodeficiency virus type 1-infected patients. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 12, 6-18.[CrossRef] [Google Scholar]
  10. Coffin, J. M. (1995). HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267, 483-489.[CrossRef] [Google Scholar]
  11. Condra, J. H., Schleif, W. A., Blahy, O. M., Gabryelski, L. J., Graham, D. J., Quintero, J. C., Rhodes, A., Robbins, H. L., Roth, E., Shivaprakash, M., Titus, D., Yang, T., Teppler, H., Squires, K. E., Deutsch, P. J. & Emini, E. A. (1995). In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 374, 569-571.[CrossRef] [Google Scholar]
  12. Condra, J. H., Holder, D. J., Schleif, W. A., Blahy, O. M., Danovich, R. M., Gabryelski, L. J., Graham, D. J., Laird, D., Quintero, J. C., Rhodes, A., Robbins, H. L., Roth, E., Shivaprakash, M., Yang, T., Chodakewitz, J. A., Deutsch, P. J., Leavitt, R. Y., Massari, F. E., Mellors, J. W., Squires, K. E., Steigbigel, R. T., Teppler, H. & Emini, E. A. (1996). Genetic correlates of in vivo viral resistance to indinavir, a human immunodeficiency virus type 1 protease inhibitor. Journal of Virology 70, 8270-8276. [Google Scholar]
  13. Delwart, E. L., Pan, H., Neumann, A. & Markowitz, M. (1998). Rapid, transient changes at the env locus of plasma human immunodeficiency virus type 1 populations during the emergence of protease inhibitor resistance. Journal of Virology 72, 2416-2421. [Google Scholar]
  14. Domingo, E., Escarmı́s, C., Sevilla, N., Moya, A., Elena, S. F., Quer, J., Novella, I. S. & Holland, J. J. (1996). Basic concepts in RNA virus evolution. FASEB Journal 10, 859-864. [Google Scholar]
  15. Domingo, E., Menendez-Arias, L., Quiñones-Mateu, M. E., Holguin, A., Gutiérrez-Rivas, M., Martı́nez, M. A., Quer, J., Novella, I. S. & Holland, J. J. (1997). Viral quasispecies and the problem of vaccine-escape and drug-resistant mutants. Progress in Drug Research 48, 99-128. [Google Scholar]
  16. Dopazo, J. (1995). Windows Easy Tree software package (version 1.3). http://www.tdi.es/programas/WET-i.html.
  17. Duarte, E. A., Clarke, D., Moya, A., Domingo, E. & Holland, J. J. (1992). Rapid fitness losses in mammalian RNA virus clones due to Muller’s ratchet. Proceedings of the National Academy of Sciences, USA 89, 6015-6019.[CrossRef] [Google Scholar]
  18. Ercoli, L., Sarmati, L., Nicastri, E., Giannini, G., Galluzzo, C., Vella, S. & Andreoni, M. (1997). HIV phenotype switching during antiretroviral therapy: emergence of saquinavir-resistant strains with less cytopathogenicity. AIDS 11, 1211-1217.[CrossRef] [Google Scholar]
  19. Escarmis, C., Dávila, M., Charpentier, N., Bracho, A., Moya, A. & Domingo, E. (1996). Genetic lesions associated with Muller’s ratchet in an RNA virus. Journal of Molecular Biology 264, 255-267.[CrossRef] [Google Scholar]
  20. Felsenstein, J. (1985). Confidence limits on phylogenies: an approach using the bootstrap. Evolution 39, 783-791.[CrossRef] [Google Scholar]
  21. Felsenstein, J. (1988). Phylogenies from molecular sequences: inference and reliability. Annual Review of Genetics 22, 521-565.[CrossRef] [Google Scholar]
  22. Felsenstein, J. (1995). Phylogeny inference package (PHYLIP), version 3.57c. University of Washington, Seattle, WA, USA. http://evolution.genetics.washington.edu/phylip.html.
  23. Gulick, R. M., Mellors, J. W., Havlir, D., Eron, J. J., Gonzalez, C., McMahon, D., Richman, D. D., Valentine, F. T., Jonas, L., Meibohm, A., Emini, E. A. & Chodakewitz, J. (1997). Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. New England Journal of Medicine 337, 734-739.[CrossRef] [Google Scholar]
  24. Hammer, S. M., Squires, K. E., Hughes, M. D., Grimes, J. M., Demeter, L. M., Currier, J. S., Eron, J. J.Jr, Feinberg, J. E., Balfour, H. H.Jr, Deyton, L. R., Chodakewitz, J. A. & Fischl, M. A. (1997). A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. New England Journal of Medicine 337, 725-733.[CrossRef] [Google Scholar]
  25. Havlir, D. V., Eastman, S., Gamst, A. & Richman, D. D. (1996). Nevirapine-resistant human immunodeficiency virus: kinetics of replication and estimated prevalence in untreated patients. Journal of Virology 70, 7894-7899. [Google Scholar]
  26. Hirsch, M. S., Conway, B., D’Aquila, R. T., Johnson, V. A., Brun-Vezinet, F., Clotet, B., Demeter, L. M., Hammer, S. M., Jacobsen, D. M., Kuritzkes, D. R., Loveday, C., Mellors, J. W., Vella, S. & Richman, D. D. (1998). Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society–USA Panel. Journal of the American Medical Association 279, 1984-1991.[CrossRef] [Google Scholar]
  27. Ho, D. D., Neumann, A. U., Perelson, A. S., Chen, W., Leonard, J. M. & Markowitz, M. (1995). Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123-126.[CrossRef] [Google Scholar]
  28. Lech, W. J., Wang, G., Yang, Y. L., Chee, Y., Dorman, K., McCrae, D., Lazzeroni, L. C., Erickson, J. W., Sinsheimer, J. S. & Kaplan, A. H. (1996). In vivo sequence diversity of the protease of human immunodeficiency virus type 1: presence of protease inhibitor-resistant variants in untreated subjects. Journal of Virology 70, 2038-2043. [Google Scholar]
  29. Leigh-Brown, A. (1997). Analysis of HIV-1 env gene sequences reveals evidence for a low effective number in the viral population Proceedings of the National Academy of Sciences, USA 94, 1862-1865.[CrossRef] [Google Scholar]
  30. Leigh-Brown, A. & Cleland, A. (1996). Independent evolution of the env and pol genes of HIV-1 during zidovudine therapy. AIDS 10, 1067-1073. [Google Scholar]
  31. Leigh-Brown, A. & Richman, D. D. (1997). HIV-1: gambling on the evolution of drug resistance? Nature Medicine 3, 268-271.[CrossRef] [Google Scholar]
  32. Liu, S. L., Schacker, T., Musey, L., Shriner, D., McElrath, M. J., Corey, L. & Mullins, J. I. (1997). Divergent patterns of progression to AIDS after infection from the same source: human immunodeficiency virus type 1 evolution and antiviral responses. Journal of Virology 71, 4284-4295. [Google Scholar]
  33. Lukashov, V. V., Kuiken, C. L. & Goudsmit, J. (1995). Intrahost human immunodeficiency virus type 1 evolution is related to length of the immunocompetent period. Journal of Virology 69, 6911-6916. [Google Scholar]
  34. Mansky, L. M. & Temin, H. M. (1995). Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. Journal of Virology 69, 5087-5094. [Google Scholar]
  35. Martı́nez, M. A., Cabana, M., Ibáñez, A., Clotet, B., Arnó, A. & Ruiz, L. (1999). Human immunodeficiency virus type 1 genetic evolution in patients with prolonged suppression of plasma viremia. Virology 256, 180-187.[CrossRef] [Google Scholar]
  36. Martı́nez-Picado, J., Savara, A. V., Sutton, L. & D’Aquila, R. T. (1999). Replicative fitness of protease inhibitor-resistant mutants of human immunodeficiency virus type 1. Journal of Virology 73, 3744-3752. [Google Scholar]
  37. Myers, G., Foley, B., Mellors, J. W., Korber, B., Jeang, K. T. & Wain-Hobson, S. (1996).Human retroviruses and AIDS database 1996. Los Alamos, NM: Theoretical Biology, Los Alamos National Laboratory.
  38. Nájera, I., Holguin, A., Quiñones-Mateu, M. E., Muñoz-Fernandez, M. A., Nájera, R., López-Galindez, C. & Domingo, E. (1995).Pol gene quasispecies of human immunodeficiency virus: mutations associated with drug resistance in virus from patients undergoing no drug therapy.Journal of Virology 69, 23-31. [Google Scholar]
  39. Nijhuis, M., Schurman, R., Jong, D. D., Schipper, P., Danner, S. & Boucher, C. (1997). Selection of HIV-1 variants with increase fitness during ritonavir therapy. In Program and Abstracts of the 1st International Workshop on HIV Drug Resistances and Treatment Strategies. St Petersburg, USA. June 1997.
  40. Nijhuis, M., Boucher, C. A., Schipper, P., Leitner, T., Schuurman, R. & Albert, J. (1998). Stochastic processes strongly influence HIV-1 evolution during suboptimal protease-inhibitor therapy. Proceedings of the National Academy of Sciences, USA 95, 14441-14446.[CrossRef] [Google Scholar]
  41. Novella, I. S., Elena, S. F., Moya, A., Domingo, E. & Holland, J. J. (1995). Size of genetic bottlenecks leading to virus fitness loss is determined by mean initial population fitness. Journal of Virology 69, 2869-2872. [Google Scholar]
  42. Page, R. D. M. (1996). TreeView: an application to display phylogenetic trees on personal computers. Computer Applications in the Biosciences 12, 357-358. [Google Scholar]
  43. Plikat, U., Nieselt-Struwe, K. & Meyerhans, A. (1997). Genetic drift can dominate short-term human immunodeficiency virus type 1 nef quasispecies evolution in vivo. Journal of Virology 71, 4233-4240. [Google Scholar]
  44. Richman, D. D. (1996). Antiretroviral drug resistance: mechanisms, pathogenesis, clinical significance. Advances in Experimental Medicine and Biology 394, 383-395. [Google Scholar]
  45. Ruiz, L., Nijhuis, M., Boucher, C., Puig, T., Bonjoch, A., Martı́nez-Picado, J., Marfil, S., de Jong, D., Burger, D., Arnó, A., Balagué, M. & Clotet, B. (1998). Efficacy of adding indinavir to previous reverse transcriptase nucleoside analogues in relation to genotypic and phenotypic resistance development in advanced HIV-1-infected patients. Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 19, 19-28.[CrossRef] [Google Scholar]
  46. Sanchez-Palomino, S., Rojas, J. M., Martı́nez, M. A., Fenyö, E. M., Nájera, R., Domingo, E. & Lopez-Galı́ndez, C. (1993). Dilute passage promotes expression of genetic and phenotypic variants of human immunodeficiency virus type 1 in cell culture. Journal of Virology 67, 2938-2943. [Google Scholar]
  47. Sanchez-Palomino, S., Olivares, I., Yuste, E., Richman, D. D. & Lopez-Galı́ndez, C. (1996). Random important alterations in HIV-1 viral quasispecies after antiviral treatment. Antiviral Therapy 4, 225-236. [Google Scholar]
  48. Shafer, R. W., Winters, M. A., Palmer, S. & Merigan, T. C. (1998). Multiple concurrent reverse transcriptase and protease mutations and multidrug resistance of HIV-1 isolates from heavily treated patients. Annals of Internal Medicine 128, 906-911.[CrossRef] [Google Scholar]
  49. Thompson, J. D., Higgins, D. G. & Gibson, T. J. (1994). CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Research 22, 4673-4680.[CrossRef] [Google Scholar]
  50. Wei, X., Ghosh, S. K., Taylor, M. E., Johnson, V. A., Emini, E. A., Deutsch, P., Lifson, J. D., Bonhoeffer, S., Nowak, M. A., Hahn, B. H., Saag, M. S. & Shaw, G. M. (1995). Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117-122.[CrossRef] [Google Scholar]
  51. Wolinsky, S. M., Korber, B. T. M., Neumann, A. U., Daniels, M., Kunstman, K. J., Whetsell, A. J., Furtado, M. R., Cao, Y., Ho, D. D., Safrit, J. T. & Koup, R. A. (1996). Adaptative evolution of human immunodeficiency virus-type 1 during the natural course of infection. Science 272, 537-542.[CrossRef] [Google Scholar]
  52. Yuste, E., Sanchez-Palomino, S., Casado, C., Domingo, E. & López-Galı́ndez, C. (1999). Drastic fitness loss in human immunodeficiency virus type 1 upon serial bottleneck events.Journal of Virology 73, 2745-2751. [Google Scholar]
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