title: Resistance-associated mutations to etravirine (TMC-125) in antiretroviral-naïve patients infected with non-B HIV-1 subtypes.
abstract: 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.
authors.affiliation: Laboratoire de Virologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, UPMC University Paris 06, INSERM U943, Paris, France.
authors.forename: Almoustapha Issiaka
authors.initials: AI
authors.lastname: Maïga
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
authors.forename: Laurence
authors.initials: L
authors.lastname: Morand-Joubert
authors.forename: Isabelle
authors.initials: I
authors.lastname: Malet
authors.forename: Anne
authors.initials: A
authors.lastname: Derache
authors.forename: Mamadou
authors.initials: M
authors.lastname: Cisse
authors.forename: Victoria
authors.initials: V
authors.lastname: Koita
authors.forename: Alain
authors.initials: A
authors.lastname: Akonde
authors.forename: Bah
authors.initials: B
authors.lastname: Diarra
authors.forename: Marc
authors.initials: M
authors.lastname: Wirden
authors.forename: Anatole
authors.initials: A
authors.lastname: Tounkara
authors.forename: Yvan
authors.initials: Y
authors.lastname: Verlinden
authors.forename: Christine
authors.initials: C
authors.lastname: Katlama
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
authors.forename: Bernard
authors.initials: B
authors.lastname: Masquelier
authors.forename: Vincent
authors.initials: V
authors.lastname: Calvez
authors.forename: Anne-Genevieve
authors.initials: AG
authors.lastname: Marcelin
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D009154:Mutation; D009570:Nitriles; D010802:Phylogeny; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; C451734:etravirine