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Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes.
J Med Virol. 2004 Jul; 73(3):350-61.JM

Abstract

HIV-1 evolution and the possible emergence of mutations associated with resistance to antiretroviral inhibitors have been evaluated in a cohort of sixty-three patients successfully treated with highly active antiretroviral therapy (HAART). The patients under effective HAART were recruited in three different hospitals in Spain, and none of them had been treated (naïve) before entering this study. HIV-1 RNA levels, CD4+, and CD8+ T-cell counts were determined, and nucleotide sequences of proviral regions encoding protease and reverse transcriptase (RT) were obtained for longitudinal blood samples spanning a mean follow-up period of 88 weeks. Phylogenetic reconstructions and calculations of genetic distances among the different sequences of each patient were performed. All except one of the patients under study showed an early and sustained decrease in plasma HIV-1 RNA to levels that were below 200 copies/ml. The plasma viral decline paralleled a significant increase in the CD4+ T-lymphocyte counts. Amino acid sequence analyses revealed the occurrence of mutations associated with antiretroviral resistance in nine patients (14.3%) during HAART treatment, that in some cases could be attributed to excess G to A transitions. In six of the nine patients, the mutations conferred resistance to inhibitors administered in the treatment regime, although the mutations did not result in treatment failure. Sequence comparisons revealed viral evolution during the period of treatment in 47.5% of the patients. The results indicate successful suppression of HIV-1 under HAART for extended time periods, indistinguishable for patients in which evidence of virus evolution could or could not be documented.

Authors+Show Affiliations

Centro de Biología Molecular Severo Ochoa, CSIC-UAM, Cantoblanco, Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15170628

Citation

Pariente, Nonia, et al. "Long-term Suppression of Plasma Viremia With Highly Active Antiretroviral Therapy Despite Virus Evolution and Very Limited Selection of Drug-resistant Genotypes." Journal of Medical Virology, vol. 73, no. 3, 2004, pp. 350-61.
Pariente N, Pernas M, de la Rosa R, et al. Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes. J Med Virol. 2004;73(3):350-61.
Pariente, N., Pernas, M., de la Rosa, R., Gómez-Mariano, G., Fernández, G., Rubio, A., López, M., Benito, J. M., López-Galíndez, C., Leal, M., Domingo, E., Martinez, M. A., & Mas, A. (2004). Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes. Journal of Medical Virology, 73(3), 350-61.
Pariente N, et al. Long-term Suppression of Plasma Viremia With Highly Active Antiretroviral Therapy Despite Virus Evolution and Very Limited Selection of Drug-resistant Genotypes. J Med Virol. 2004;73(3):350-61. PubMed PMID: 15170628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term suppression of plasma viremia with highly active antiretroviral therapy despite virus evolution and very limited selection of drug-resistant genotypes. AU - Pariente,Nonia, AU - Pernas,María, AU - de la Rosa,Rafael, AU - Gómez-Mariano,Gema, AU - Fernández,Guerau, AU - Rubio,Amalia, AU - López,Mariola, AU - Benito,José Miguel, AU - López-Galíndez,Cecilio, AU - Leal,Manuel, AU - Domingo,Esteban, AU - Martinez,Miguel Angel, AU - Mas,Antonio, PY - 2004/6/2/pubmed PY - 2004/12/22/medline PY - 2004/6/2/entrez SP - 350 EP - 61 JF - Journal of medical virology JO - J Med Virol VL - 73 IS - 3 N2 - HIV-1 evolution and the possible emergence of mutations associated with resistance to antiretroviral inhibitors have been evaluated in a cohort of sixty-three patients successfully treated with highly active antiretroviral therapy (HAART). The patients under effective HAART were recruited in three different hospitals in Spain, and none of them had been treated (naïve) before entering this study. HIV-1 RNA levels, CD4+, and CD8+ T-cell counts were determined, and nucleotide sequences of proviral regions encoding protease and reverse transcriptase (RT) were obtained for longitudinal blood samples spanning a mean follow-up period of 88 weeks. Phylogenetic reconstructions and calculations of genetic distances among the different sequences of each patient were performed. All except one of the patients under study showed an early and sustained decrease in plasma HIV-1 RNA to levels that were below 200 copies/ml. The plasma viral decline paralleled a significant increase in the CD4+ T-lymphocyte counts. Amino acid sequence analyses revealed the occurrence of mutations associated with antiretroviral resistance in nine patients (14.3%) during HAART treatment, that in some cases could be attributed to excess G to A transitions. In six of the nine patients, the mutations conferred resistance to inhibitors administered in the treatment regime, although the mutations did not result in treatment failure. Sequence comparisons revealed viral evolution during the period of treatment in 47.5% of the patients. The results indicate successful suppression of HIV-1 under HAART for extended time periods, indistinguishable for patients in which evidence of virus evolution could or could not be documented. SN - 0146-6615 UR - https://www.unboundmedicine.com/medline/citation/15170628/Long_term_suppression_of_plasma_viremia_with_highly_active_antiretroviral_therapy_despite_virus_evolution_and_very_limited_selection_of_drug_resistant_genotypes_ L2 - https://doi.org/10.1002/jmv.20098 DB - PRIME DP - Unbound Medicine ER -