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Long-term analysis of the resistance development in HIV-1 positive patients treated with protease and reverse transcriptase inhibitors: correlation of the genotype and disease progression
J. Václavíková, J. Weber, L. Machala, M. Reiniš, M. Linka, M. Brůčková, J. Vandasová, M. Staňková, J. Konvalinka
Language English Country Slovakia
NLK
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from 1995
- MeSH
- Financing, Organized MeSH
- Genotype MeSH
- HIV Infections drug therapy virology MeSH
- HIV Reverse Transcriptase genetics MeSH
- HIV-1 genetics isolation & purification drug effects MeSH
- HIV Protease genetics MeSH
- HIV Protease Inhibitors administration & dosage therapeutic use MeSH
- Anti-HIV Agents administration & dosage therapeutic use MeSH
- Humans MeSH
- CD4 Lymphocyte Count MeSH
- Disease Progression MeSH
- Amino Acid Substitution MeSH
- Drug Resistance, Viral genetics MeSH
- Antiretroviral Therapy, Highly Active MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Geographicals
- Czech Republic MeSH
In this study, 27 HIV-1-positive patients on long-term highly active antiretroviral therapy (HAART) in the Czech Republic were followed for a period of up to 7 years. Variability of the HIV-1 protease (PR) sequence common in the Czech Republic was observed. Under the pressure of inhibitors of protease (PRIs) and reverse transcriptase (RTIs) mutations in PR were detected. Development of resistance to PRIs was followed by a decrease in CD4 count and increase in viral load. The dynamics of viral load closely corresponded to the accumulation of specific primary mutations in PR and RT. Out of 27 patients 18 developed resistance to PRIs and the prolonged therapy led to the accumulation of a higher number of amino acid changes associated with the resistance and, consequently, cross-resistance to several PRIs was observed. These multi-resistant variants of HIV-1 with mutations in PR could not be inhibited sufficiently with PRIs that are currently available in clinical practice. Efficient yet temporary suppression of viral replication was achieved by a lopinavir (LPV) treatment.
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- $a In this study, 27 HIV-1-positive patients on long-term highly active antiretroviral therapy (HAART) in the Czech Republic were followed for a period of up to 7 years. Variability of the HIV-1 protease (PR) sequence common in the Czech Republic was observed. Under the pressure of inhibitors of protease (PRIs) and reverse transcriptase (RTIs) mutations in PR were detected. Development of resistance to PRIs was followed by a decrease in CD4 count and increase in viral load. The dynamics of viral load closely corresponded to the accumulation of specific primary mutations in PR and RT. Out of 27 patients 18 developed resistance to PRIs and the prolonged therapy led to the accumulation of a higher number of amino acid changes associated with the resistance and, consequently, cross-resistance to several PRIs was observed. These multi-resistant variants of HIV-1 with mutations in PR could not be inhibited sufficiently with PRIs that are currently available in clinical practice. Efficient yet temporary suppression of viral replication was achieved by a lopinavir (LPV) treatment.
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