title: Archived HIV-1 DNA resistance mutations to rilpivirine and etravirine in successfully treated HIV-1-infected individuals pre-exposed to efavirenz or nevirapine.
abstract: OBJECTIVE
  Efavirenz and nevirapine failure is associated with a rapid selection of resistance-associated mutations (RAMs), which may impact on etravirine or rilpivirine susceptibility. However, RAMs for rilpivirine and etravirine cannot be reported on previous resistance genotypes because these specific RAMs were not analyzed at that time. Therefore, our objective was to determine, in virologically suppressed HIV-1-infected individuals, the presence of RAMs to rilpivirine, etravirine and the combination of tenofovir/emtricitabine/rilpivirine in HIV-1 DNA from individuals previously exposed to efavirenz and/or nevirapine.
  
  
  METHODS
  The studied population included 169 treatment-experienced individuals enrolled in the ANRS 138-EASIER trial who previously failed on and/or were intolerant to efavirenz and/or nevirapine and who had plasma HIV-1 RNA<400 copies/mL. Resistance to rilpivirine, etravirine, tenofovir and emtricitabine by bulk sequencing was performed on extracted HIV-1 DNA from whole blood collected at the time of trial inclusion.
  
  
  RESULTS
  Reverse transcriptase gene amplification was successful in 128/169 (76%) individuals and 95% of HIV-1 were infected with subtype B. Rilpivirine RAMs were detected in 41 (32%) individuals, with highest frequency for the mutations Y181C/I/V (18%), K101E/P (7%) and E138A/G/K/Q/R/S (6%) and the association L100I+K103N/S (5%). Etravirine RAMs were detected in five (4%) individuals. Resistance to emtricitabine, tenofovir and at least one drug included in the combination of tenofovir/emtricitabine/rilpivirine were detected in 72 (56%), 12 (9%) and 88 (69%), respectively.
  
  
  CONCLUSIONS
  In individuals with suppressed viraemia under antiretroviral therapy (ART), but who had been previously exposed to an efavirenz and/or nevirapine-based regimen, rilpivirine RAMs are frequent and etravirine RAMs are rare. This finding suggests that the switch to a rilpivirine-based regimen should not be recommended.
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Louis-APHP, Paris, France INSERM U941, Université Paris Diderot, Sorbonne Paris Cité, Paris, France sebastien.gallien@sls.aphp.fr.
authors.forename: S
authors.initials: S
authors.lastname: Gallien
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: I
authors.initials: I
authors.lastname: Charreau
authors.affiliation: Laboratoire de Virologie, Hôpital Saint Louis-APHP, Paris, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Nere
authors.affiliation: Laboratoire de Virologie, Hôpital Saint Louis-APHP, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: Mahjoub
authors.affiliation: INSERM U941, Université Paris Diderot, Sorbonne Paris Cité, Paris, France Laboratoire de Virologie, Hôpital Saint Louis-APHP, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Simon
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Louis-APHP, Paris, France.
authors.forename: N
authors.initials: N
authors.lastname: de Castro
authors.affiliation: INSERM SC10, Villejuif, France.
authors.forename: J P
authors.initials: JP
authors.lastname: Aboulker
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Hôpital Saint-Louis-APHP, Paris, France INSERM U941, Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: J M
authors.initials: JM
authors.lastname: Molina
authors.affiliation: INSERM U941, Université Paris Diderot, Sorbonne Paris Cité, Paris, France Laboratoire de Virologie, Hôpital Saint Louis-APHP, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Delaugerre
mesh_terms: D000328:Adult; D000368:Aged; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009154:Mutation; D019829:Nevirapine / Q000627:therapeutic use; D009570:Nitriles / Q000494:pharmacology / Q000627:therapeutic use*; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D019233:Retreatment; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000068696:Rilpivirine; D055815:Young Adult
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C451734:etravirine; D019829:Nevirapine; D000068696:Rilpivirine; C098320:efavirenz
keywords: HIV; NNRTIs; antiviral