Changes in Human Immunodeficiency Virus Type 1 Populations after Treatment Interruption in Patients Failing Antiretroviral Therapy

doi:10.1128/JVI.75.14.6410-6417.2001

This Article

	Full Text
	Full Text (PDF)
	Alert me when this article is cited
	Alert me if a correction is posted

Services

	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new issues of the journal
	Download to citation manager
	Reprints and Permissions
	Copyright Information
	Books from ASM Press
	MicrobeWorld

Citing Articles

	Citing Articles via HighWire
	Citing Articles via Google Scholar

Google Scholar

	Articles by Hance, A. J.
	Articles by Clavel, F.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Hance, A. J.
	Articles by Clavel, F.

Previous Article | Next Article

Journal of Virology, July 2001, p. 6410-6417, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6410-6417.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Changes in Human Immunodeficiency Virus Type 1 Populations after Treatment Interruption in Patients Failing Antiretroviral Therapy

Allan J. Hance,¹^,^* Virginie Lemiale,¹ Jacques Izopet,² Denise Lecossier,¹ Véronique Joly,³ Patrice Massip,² Fabrizio Mammano,¹ Diane Descamps,⁴ Françoise Brun-Vézinet,⁴ and François Clavel¹

INSERM U552,¹ Service des Maladies Infectieuses et Tropicales A,³ and Laboratoire de Virologie,⁴ Hôpital Bichat-Claude Bernard, Paris, and Centre Hospitalier Universitaire Purpan, Toulouse,² France

Received 7 December 2000/Accepted 12 April 2001

Mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and protease that confer resistance to antiretroviralagents are usually accompanied by a reduction in the viral replicativecapacity under drug-free conditions. Consequently, when antiretroviraltreatment is interrupted in HIV-1-infected patients harboringdrug-resistant virus, resistant quasi-species appear to be mostoften replaced within several weeks by wild-type virus. Usinga real-time PCR-based technique for the selective quantificationof resistant viral sequences in plasma, we have studied the kineticsof the switch from mutant to wild-type virus and evaluated theextent to which minority populations of resistant viruses notdetected by genotyping persist in these individuals. Among 12patients with viruses expressing the V82A or L90M resistance mutationwho had undergone a 3-month interruption of therapy and for whomconventional genotyping had revealed an apparent total reconversionto wild-type virus, minority populations expressing these mutations,representing 0.1 to 21% of total virus, were still detectablein 9 cases. Kinetic studies demonstrated that viruses expressingresistance mutations could be detected for >5 months after thediscontinuation of treatment in some patients. Most of the minorityresistant genomes detected more than 3 months after the interruptionof therapy carried only part of the mutations present in the resistantviruses prior to treatment interruption and appeared to resultfrom the emergence of existing strains selected at earlier stagesin the development of drug resistance. Thus, following the interruptionof treatment, viral populations containing resistance mutationscan persist for several months after the time when conventionalgenotyping techniques detect only wild-type virus. These populationsinclude viral strains with only some of the resistance mutationsinitially present, strains that presumably express better fitnessunder drug-freeconditions.

^* Corresponding author. Mailing address: INSERM U552, IMEA-INSERM, Hôpital Bichat-Claude Bernard, 46, rue Henri Huchard, 75018Paris, France. Phone: 33-1-40-25-63-55. Fax: 33-1-40-25-63-70.E-mail: hance{at}bichat.inserm.fr.

Journal of Virology, July 2001, p. 6410-6417, Vol. 75, No. 14
0022-538X/01/$04.00+0 DOI: 10.1128/JVI.75.14.6410-6417.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

This article has been cited by other articles:

Xu, Z., Fan, X., Xu, Y., Di Bisceglie, A. M. (2008). Comparative Analysis of Nearly Full-Length Hepatitis C Virus Quasispecies from Patients Experiencing Viral Breakthrough during Antiviral Therapy: Clustered Mutations in Three Functional Genes, E2, NS2, and NS5a. J. Virol. 82: 9417-9424 [Abstract] [Full Text]
Detsika, M. G., Chandler, B., Khoo, S. H., Winstanley, C., Cane, P., Back, D. J., Owen, A. (2007). Detection and quantification of minority HIV isolates harbouring the D30N mutation by real-time PCR amplification. J Antimicrob Chemother 60: 881-884 [Abstract] [Full Text]
Wang, C., Mitsuya, Y., Gharizadeh, B., Ronaghi, M., Shafer, R. W. (2007). Characterization of mutation spectra with ultra-deep pyrosequencing: Application to HIV-1 drug resistance. Genome Res 17: 1195-1201 [Abstract] [Full Text]
Healy, B., Degruttola, V. (2007). Hidden Markov models for settings with interval-censored transition times and uncertain time origin: application to HIV genetic analyses. Biostatistics 8: 438-452 [Abstract] [Full Text]
Halvas, E. K., Aldrovandi, G. M., Balfe, P., Beck, I. A., Boltz, V. F., Coffin, J. M., Frenkel, L. M., Hazelwood, J. D., Johnson, V. A., Kearney, M., Kovacs, A., Kuritzkes, D. R., Metzner, K. J., Nissley, D. V., Nowicki, M., Palmer, S., Ziermann, R., Zhao, R. Y., Jennings, C. L., Bremer, J., Brambilla, D., Mellors, J. W. (2006). Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency.. J. Clin. Microbiol. 44: 2612-2614 [Abstract] [Full Text]
Resch, W., Parkin, N., Watkins, T., Harris, J., Swanstrom, R. (2005). Evolution of Human Immunodeficiency Virus Type 1 Protease Genotypes and Phenotypes In Vivo under Selective Pressure of the Protease Inhibitor Ritonavir. J. Virol. 79: 10638-10649 [Abstract] [Full Text]
Delaunay, C., Brun-Vezinet, F., Landman, R., Collin, G., Peytavin, G., Trylesinski, A., Flandre, P., Miller, M., Descamps, D., the Tonus Trial Study Group, (2005). Comparative Selection of the K65R and M184V/I Mutations in Human Immunodeficiency Virus Type 1-Infected Patients Enrolled in a Trial of First-Line Triple-Nucleoside Analog Therapy (Tonus IMEA 021). J. Virol. 79: 9572-9578 [Abstract] [Full Text]
Sullivan, S. T., Mandava, U., Evans-Strickfaden, T., Lennox, J. L., Ellerbrock, T. V., Hart, C. E. (2005). Diversity, Divergence, and Evolution of Cell-Free Human Immunodeficiency Virus Type 1 in Vaginal Secretions and Blood of Chronically Infected Women: Associations with Immune Status. J. Virol. 79: 9799-9809 [Abstract] [Full Text]
Senescau, A., Berry, A., Benoit-Vical, F., Landt, O., Fabre, R., Lelievre, J., Cassaing, S., Magnaval, J.-F. (2005). Use of a Locked-Nucleic-Acid Oligomer in the Clamped-Probe Assay for Detection of a Minority Pfcrt K76T Mutant Population of Plasmodium falciparum. J. Clin. Microbiol. 43: 3304-3308 [Abstract] [Full Text]
Palmer, S., Kearney, M., Maldarelli, F., Halvas, E. K., Bixby, C. J., Bazmi, H., Rock, D., Falloon, J., Davey, R. T. Jr., Dewar, R. L., Metcalf, J. A., Hammer, S., Mellors, J. W., Coffin, J. M. (2005). Multiple, Linked Human Immunodeficiency Virus Type 1 Drug Resistance Mutations in Treatment-Experienced Patients Are Missed by Standard Genotype Analysis. J. Clin. Microbiol. 43: 406-413 [Abstract] [Full Text]
Mo, H., Lu, L., Pithawalla, R., Kempf, D. J., Molla, A. (2004). Complementation in Cells Cotransfected with a Mixture of Wild-Type and Mutant Human Immunodeficiency Virus (HIV) Influences the Replication Capacities and Phenotypes of Mutant Variants in a Single-Cycle HIV Resistance Assay. J. Clin. Microbiol. 42: 4169-4174 [Abstract] [Full Text]
Kapoor, A., Jones, M., Shafer, R. W., Rhee, S.-Y., Kazanjian, P., Delwart, E. L. (2004). Sequencing-Based Detection of Low-Frequency Human Immunodeficiency Virus Type 1 Drug-Resistant Mutants by an RNA/DNA Heteroduplex Generator-Tracking Assay. J. Virol. 78: 7112-7123 [Abstract] [Full Text]
Charpentier, C., Dwyer, D. E., Mammano, F., Lecossier, D., Clavel, F., Hance, A. J. (2004). Role of Minority Populations of Human Immunodeficiency Virus Type 1 in the Evolution of Viral Resistance to Protease Inhibitors. J. Virol. 78: 4234-4247 [Abstract] [Full Text]
Clavel, F., Hance, A. J. (2004). HIV Drug Resistance. NEJM 350: 1023-1035 [Full Text]
Goodenow, M. M., Rose, S. L., Tuttle, D. L., Sleasman, J. W. (2003). HIV-1 fitness and macrophages. J. Leukoc. Biol. 74: 657-666 [Abstract] [Full Text]
Weber, J., Rangel, H. R., Chakraborty, B., Tadele, M., Martinez, M. A., Martinez-Picado, J., Marotta, M. L., Mirza, M., Ruiz, L., Clotet, B., Wrin, T., Petropoulos, C. J., Quinones-Mateu, M. E. (2003). A novel TaqMan real-time PCR assay to estimate ex vivo human immunodeficiency virus type 1 fitness in the era of multi-target (pol and env) antiretroviral therapy. J. Gen. Virol. 84: 2217-2228 [Abstract] [Full Text]
Simon, V., Padte, N., Murray, D., Vanderhoeven, J., Wrin, T., Parkin, N., Di Mascio, M., Markowitz, M. (2003). Infectivity and Replication Capacity of Drug-Resistant Human Immunodeficiency Virus Type 1 Variants Isolated during Primary Infection. J. Virol. 77: 7736-7745 [Abstract] [Full Text]
Barbour, J. D., Wrin, T., Grant, R. M., Martin, J. N., Segal, M. R., Petropoulos, C. J., Deeks, S. G. (2002). Evolution of Phenotypic Drug Susceptibility and Viral Replication Capacity during Long-Term Virologic Failure of Protease Inhibitor Therapy in Human Immunodeficiency Virus-Infected Adults. J. Virol. 76: 11104-11112 [Abstract] [Full Text]
Yeni, P. G., Hammer, S. M., Carpenter, C. C. J., Cooper, D. A., Fischl, M. A., Gatell, J. M., Gazzard, B. G., Hirsch, M. S., Jacobsen, D. M., Katzenstein, D. A., Montaner, J. S. G., Richman, D. D., Saag, M. S., Schechter, M., Schooley, R. T., Thompson, M. A., Vella, S., Volberding, P. A. (2002). Antiretroviral Treatment for Adult HIV Infection in 2002: Updated Recommendations of the International AIDS Society-USA Panel. JAMA 288: 222-235 [Abstract] [Full Text]

J. Bacteriol.	Mol. Cell. Biol.	Microbiol. Mol. Biol. Rev.

Clin. Vaccine Immunol.	ALL ASM JOURNALS