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Virological significance, prevalence and genetic basis of hypersusceptibility to nonnucleoside reverse transcriptase inhibitors

Virological significance, prevalence and genetic basis of hypersusceptibility to nonnucleoside... Nonnucleoside reverse transcriptase inhibitors (NNRTI) are used to treat HIV-infected individuals in combination with nucleoside analogues (NRTI) and protease inhibitors. Long-term treatment with antiretroviral agents results in the emergence of strains with decreased susceptibility (resistance) to the drugs and is one of the major factors in loss of drug efficacy. Conversely, there have been recent reports of HIV strains with increased susceptibility (hypersusceptibility) to NNRTIs. These isolates emerge in patients on long-term antiretroviral therapy particularly in individuals receiving NRTIs. The prevalence of NNRTI hypersusceptibility ranges between 17.5 and 50% in NRTI-treatment experienced compared to 10% in NRTI-naïve patients. There is an inverse correlation between NNRTI hypersusceptibility and phenotypic NRTI resistance and a direct correlation between the number of NRTI resistance mutations present in the HIV reverse transcriptase. Re-sensitisation of phenotypic NNRTI resistance has been reported by NRTI mutations and is not likely to be detected using genotypic resistance assays. Recent studies demonstrate that NNRTI hypersusceptible virus at baseline is likely to predict better virological outcomes in patients on NNRTI-based salvage regimens compared to patients with NNRTI susceptible virus. These studies have implications for the sequence of antiretroviral drug use where patients may benefit from NRTI therapy before the introduction of NNRTIs, however more studies are needed to examine this treatment rationale. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Sexual Health CSIRO Publishing

Virological significance, prevalence and genetic basis of hypersusceptibility to nonnucleoside reverse transcriptase inhibitors

Sexual Health , Volume 1 (2) – Jun 24, 2004

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References (73)

Publisher
CSIRO Publishing
Copyright
CSIRO
ISSN
1448-5028
eISSN
1449-8987
DOI
10.1071/SH03012
Publisher site
See Article on Publisher Site

Abstract

Nonnucleoside reverse transcriptase inhibitors (NNRTI) are used to treat HIV-infected individuals in combination with nucleoside analogues (NRTI) and protease inhibitors. Long-term treatment with antiretroviral agents results in the emergence of strains with decreased susceptibility (resistance) to the drugs and is one of the major factors in loss of drug efficacy. Conversely, there have been recent reports of HIV strains with increased susceptibility (hypersusceptibility) to NNRTIs. These isolates emerge in patients on long-term antiretroviral therapy particularly in individuals receiving NRTIs. The prevalence of NNRTI hypersusceptibility ranges between 17.5 and 50% in NRTI-treatment experienced compared to 10% in NRTI-naïve patients. There is an inverse correlation between NNRTI hypersusceptibility and phenotypic NRTI resistance and a direct correlation between the number of NRTI resistance mutations present in the HIV reverse transcriptase. Re-sensitisation of phenotypic NNRTI resistance has been reported by NRTI mutations and is not likely to be detected using genotypic resistance assays. Recent studies demonstrate that NNRTI hypersusceptible virus at baseline is likely to predict better virological outcomes in patients on NNRTI-based salvage regimens compared to patients with NNRTI susceptible virus. These studies have implications for the sequence of antiretroviral drug use where patients may benefit from NRTI therapy before the introduction of NNRTIs, however more studies are needed to examine this treatment rationale.

Journal

Sexual HealthCSIRO Publishing

Published: Jun 24, 2004

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