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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes
Antimicrobial Agents and Chemotherapy, Volume 54, No. 2, Year 2010
Notification
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Description
Susceptibility to etravirine (ETR), an expanded-spectrum nonnucleoside reverse transcriptase inhibitor (NNRTI), is dependent on the type and number of NNRTI resistance-associated mutations (RAMs). Studies have shown that some HIV-1 subtypes may have natural polymorphisms described as ETR RAMs. This study addresses the prevalence of ETR RAMs in treatment-naïve patients infected with HIV-1 non-B subtypes and its potential impact on ETR susceptibility. The prevalence of ETR RAMs in 726 antiretroviral-naïve patients infected with non-B HIV-1 subtypes was studied. ETR genotypic resistance was interpreted according to Agence Nationale de Recherches sur le SIDA and Stanford algorithms. NNRTI phenotypic susceptibilities of samples with at least one ETR RAM were measured. Overall, 75 (10.3%) of 726 sequences harbored at least one ETR RAM: sequences from 72 patients (10%) each had one ETR RAM, and sequences from 3 patients (0.4%) each had two ETR RAMs (V90I and Y181C in one case and V90I and A98G in two cases). None of the viruses had three or more ETR RAMs, and none were consequently classified as resistant to ETR. All sequences with two ETR RAMs belonged to subtype CRF02-AG. The presence of one ETR RAM was statistically more frequent in subtype CRF02-AG than in other non-B subtypes (P = 0.004). Three new mutation profiles (E138A and V179I, Y181C and H221Y, and V90I and Y181C) showing decreased ETR phenotypic susceptibility were identified. In conclusion, although the prevalence of ETR RAMs in treatment-naïve patients infected with non-B HIV-1 subtypes was 10%, in most cases this had no significant impact on ETR susceptibility. However, the transmission of drug-resistant viruses with Y181C in a non-B genetic background has a potential for impact on ETR susceptibility. Copyright © 2010, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
Maïga, Almoustapha Issiaka
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Mali, Bamako
University of Bamako
Descamps, Diáne
France, Paris
Hôpital Bichat-claude-bernard Ap-hp
Morand-Joubert, Laurence
France, Paris
Hôpital Saint-antoine
Malet, Isabelle
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Derache, Anne
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Cissé, Mamadou C.
Mali, Bamako
Cesac
Koita, Victoria
Mali, Bamako
Cesac
Akonde, Alain
Unknown Affiliation
Diarra, B.
Mali
Hôpital Nianankoro Fomba
Wirden, Marc
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Tounkara, Anatole
Mali, Bamako
University of Bamako
Verlinden, Yvan
Belgium, Mechelen
Virco Bvba
Katlama, Christine
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Costagliola, Dominique G.
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Masquelier, Bernard
France, Talence
Centre Hospitalier Universitaire de Bordeaux
Calvez, Vincent
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Marcelin, Anne Geneviève
France, Paris
Hôpital Universitaire Pitié Salpêtrière
Statistics
Citations: 47
Authors: 17
Affiliations: 8
Identifiers
Doi:
10.1128/AAC.01335-09
ISSN:
00664804
e-ISSN:
10986596
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study