PittsburghV1, PubMed, Checkpoint, bibRecord, 003143

E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings.

Identifieur interne : 003143 ( PubMed/Checkpoint ); précédent : 003142; suivant : 003144

E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings.

Auteurs : Nicolas Sluis-Cremer [États-Unis] ; Michael R. Jordan [États-Unis] ; Kelly Huber [États-Unis] ; Carole L. Wallis [Afrique du Sud] ; Silvia Bertagnolio [Suisse] ; John W. Mellors [États-Unis] ; Neil T. Parkin [États-Unis] ; P Richard Harrigan [Canada]

Source :

Antiviral research [ 1872-9096 ] ; 2014.

RBID : pubmed:24746459

Descripteurs français

KwdFr :
- Agents antiVIH (pharmacologie), Humains, Infections à VIH (traitement médicamenteux), Infections à VIH (virologie), Mutation faux-sens, Nitriles (pharmacologie), Pyrimidines (pharmacologie), Rilpivirine, Résistance virale aux médicaments, Substitution d'acide aminé, Transcriptase inverse du VIH (génétique), Transcriptase inverse du VIH (métabolisme), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (enzymologie), VIH-1 (Virus de l'Immunodéficience Humaine de type 1) (génétique).
MESH :
- enzymologie : VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- génétique : Transcriptase inverse du VIH, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).
- métabolisme : Transcriptase inverse du VIH.
- pharmacologie : Agents antiVIH, Nitriles, Pyrimidines.
- traitement médicamenteux : Infections à VIH.
- virologie : Infections à VIH.
- Humains, Mutation faux-sens, Rilpivirine, Résistance virale aux médicaments, Substitution d'acide aminé, VIH-1 (Virus de l'Immunodéficience Humaine de type 1).

English descriptors

KwdEn :
- Amino Acid Substitution, Anti-HIV Agents (pharmacology), Drug Resistance, Viral, HIV Infections (drug therapy), HIV Infections (virology), HIV Reverse Transcriptase (genetics), HIV Reverse Transcriptase (metabolism), HIV-1 (classification), HIV-1 (enzymology), HIV-1 (genetics), Humans, Mutation, Missense, Nitriles (pharmacology), Pyrimidines (pharmacology), Rilpivirine.
MESH :
- chemical , genetics : HIV Reverse Transcriptase.
- chemical , metabolism : HIV Reverse Transcriptase.
- chemical , pharmacology : Anti-HIV Agents, Nitriles, Pyrimidines.
- classification : HIV-1.
- drug therapy : HIV Infections.
- enzymology : HIV-1.
- genetics : HIV-1.
- virology : HIV Infections.
- Amino Acid Substitution, Drug Resistance, Viral, Humans, Mutation, Missense, Rilpivirine.

Abstract

The nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV) has been co-formulated with emtricitabine and tenofovir disoproxil fumarate for initial therapy of HIV-1-infected individuals. RPV, formulated as a long-acting nanosuspension, will also be assessed for its ability to prevent HIV-1 infection in resource limited settings. In this study, we determined whether any pre-existing genetic differences occurred among different HIV-1 subtypes at residues in RT associated with decreased virologic response to RPV. We found that the E138A substitution occurs more frequently in subtype C (range: 5.9-7.5%) than B (range: 0-2.3%) sequences from both treatment-naïve and -experienced individuals (p<0.01) in 4 independent genotype databases. In one of the databases (Stanford University), E138K and E138Q were also more common in RTI-experienced subtype C sequences (1.0% and 1.1%, respectively) than in subtype B sequences (0.3% and 0.6%, respectively). E138A/K/Q in subtype C decreased RPV susceptibility 2.9-, 5.8-, and 5.4-fold, respectively. Taken together, these data suggest that E138A could impact treatment or prevention strategies that include RPV in geographic areas where subtype C infection is prevalent.

DOI: 10.1016/j.antiviral.2014.04.001
PubMed: 24746459

Affiliations:

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<front><div type="abstract" xml:lang="en">The nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV) has been co-formulated with emtricitabine and tenofovir disoproxil fumarate for initial therapy of HIV-1-infected individuals. RPV, formulated as a long-acting nanosuspension, will also be assessed for its ability to prevent HIV-1 infection in resource limited settings. In this study, we determined whether any pre-existing genetic differences occurred among different HIV-1 subtypes at residues in RT associated with decreased virologic response to RPV. We found that the E138A substitution occurs more frequently in subtype C (range: 5.9-7.5%) than B (range: 0-2.3%) sequences from both treatment-naïve and -experienced individuals (p<0.01) in 4 independent genotype databases. In one of the databases (Stanford University), E138K and E138Q were also more common in RTI-experienced subtype C sequences (1.0% and 1.1%, respectively) than in subtype B sequences (0.3% and 0.6%, respectively). E138A/K/Q in subtype C decreased RPV susceptibility 2.9-, 5.8-, and 5.4-fold, respectively. Taken together, these data suggest that E138A could impact treatment or prevention strategies that include RPV in geographic areas where subtype C infection is prevalent.</div>
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<Abstract><AbstractText>The nonnucleoside reverse transcriptase (RT) inhibitor rilpivirine (RPV) has been co-formulated with emtricitabine and tenofovir disoproxil fumarate for initial therapy of HIV-1-infected individuals. RPV, formulated as a long-acting nanosuspension, will also be assessed for its ability to prevent HIV-1 infection in resource limited settings. In this study, we determined whether any pre-existing genetic differences occurred among different HIV-1 subtypes at residues in RT associated with decreased virologic response to RPV. We found that the E138A substitution occurs more frequently in subtype C (range: 5.9-7.5%) than B (range: 0-2.3%) sequences from both treatment-naïve and -experienced individuals (p<0.01) in 4 independent genotype databases. In one of the databases (Stanford University), E138K and E138Q were also more common in RTI-experienced subtype C sequences (1.0% and 1.1%, respectively) than in subtype B sequences (0.3% and 0.6%, respectively). E138A/K/Q in subtype C decreased RPV susceptibility 2.9-, 5.8-, and 5.4-fold, respectively. Taken together, these data suggest that E138A could impact treatment or prevention strategies that include RPV in geographic areas where subtype C infection is prevalent.</AbstractText>
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<CommentsCorrections RefType="Cites"><RefSource>AIDS. 2013 Jan 2;27(1):81-5</RefSource>
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E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings.

E138A in HIV-1 reverse transcriptase is more common in subtype C than B: implications for rilpivirine use in resource-limited settings.

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