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Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy

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Abstract
The aim of this study was to determine whether drug-resistant virus persists in peripheral blood mononuclear cells (PBMCs) after long-term suppression of virus replication. Proviral DNA was extracted from the PBMCs of I I patients on long-term highly active antiretroviral therapy (HAART). Genotyping of the reverse transcriptase (RT) and protease gene of several proviral variants was performed using limiting dilution polyincrase chain reaction and single-copy sequencing. All patients were on successful HAART for a mean period of 59 months but had a history of suboptimal therapy and genotypic drug resistance before. Comparison of the amino acid sequence of the RT and protease gene in the different proviral variants, with that of the plasma virus isolated before HAART treatment, revealed that the different drug-resistant viral variants that evolved during the process of gradually building up resistance were still detectable in the PBMCs in 10 of the 11 patients tested. The proportion of resistant variants was found to correlate with the time that the resistant variants had been able to replicate. These data clearly show that virus variants that are able to replicate for a certain period enter the latent reservoir and remain archived in the PBMCs for a very long period.

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Chicago
Verhofstede, Chris, Anne Noë, Els Demecheleer, Nancy De Cabooter, Filip Van Wanzeele, Beatrijs Van Der Gucht, Dirk Vogelaers, and Jean Plum. 2004. “Drug-resistant Variants That Evolve During Nonsuppressive Therapy Persist in HIV-1-infected Peripheral Blood Mononuclear Cells After Long-term Highly Active Antiretroviral Therapy.” Jaids-journal of Acquired Immune Deficiency Syndromes 35 (5): 473–483.
APA
Verhofstede, C., Noë, A., Demecheleer, E., De Cabooter, N., Van Wanzeele, F., Van Der Gucht, B., Vogelaers, D., et al. (2004). Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 35(5), 473–483.
Vancouver
1.
Verhofstede C, Noë A, Demecheleer E, De Cabooter N, Van Wanzeele F, Van Der Gucht B, et al. Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy. JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES. LIPPINCOTT WILLIAMS & WILKINS; 2004;35(5):473–83.
MLA
Verhofstede, Chris, Anne Noë, Els Demecheleer, et al. “Drug-resistant Variants That Evolve During Nonsuppressive Therapy Persist in HIV-1-infected Peripheral Blood Mononuclear Cells After Long-term Highly Active Antiretroviral Therapy.” JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES 35.5 (2004): 473–483. Print.
@article{218261,
  abstract     = {The aim of this study was to determine whether drug-resistant virus persists in peripheral blood mononuclear cells (PBMCs) after long-term suppression of virus replication. Proviral DNA was extracted from the PBMCs of I I patients on long-term highly active antiretroviral therapy (HAART). Genotyping of the reverse transcriptase (RT) and protease gene of several proviral variants was performed using limiting dilution polyincrase chain reaction and single-copy sequencing. All patients were on successful HAART for a mean period of 59 months but had a history of suboptimal therapy and genotypic drug resistance before. Comparison of the amino acid sequence of the RT and protease gene in the different proviral variants, with that of the plasma virus isolated before HAART treatment, revealed that the different drug-resistant viral variants that evolved during the process of gradually building up resistance were still detectable in the PBMCs in 10 of the 11 patients tested. The proportion of resistant variants was found to correlate with the time that the resistant variants had been able to replicate. These data clearly show that virus variants that are able to replicate for a certain period enter the latent reservoir and remain archived in the PBMCs for a very long period.},
  author       = {Verhofstede, Chris and No{\"e}, Anne and Demecheleer, Els and De Cabooter, Nancy and Van Wanzeele, Filip and Van Der Gucht, Beatrijs and Vogelaers, Dirk and Plum, Jean},
  issn         = {1525-4135},
  journal      = {JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES},
  language     = {eng},
  number       = {5},
  pages        = {473--483},
  publisher    = {LIPPINCOTT WILLIAMS \& WILKINS},
  title        = {Drug-resistant variants that evolve during nonsuppressive therapy persist in HIV-1-infected peripheral blood mononuclear cells after long-term highly active antiretroviral therapy},
  volume       = {35},
  year         = {2004},
}

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