title: Minority variants associated with resistance to HIV-1 nonnucleoside reverse transcriptase inhibitors during primary infection.
abstract: BACKGROUND
  Recent data suggest that subjects harbouring low-frequency variants of HIV that are resistant to non-nucleoside reverse-transcriptase inhibitors (NNRTI) could suffer virological failure when treated with NNRTI-based therapy. Rilpivirine, a second-generation NNRTI, will be used in first-line regimen therapy, but the prevalence of minority variants that are resistant to rilpivirine is unknown.
  
  
  OBJECTIVE
  We evaluated the presence of low-frequency NNRTI resistance associated mutations (RAMs) in 27 patients with a primary HIV-1 infection.
  
  
  METHODS
  We performed genotypic resistance test at baseline and used ultradeep pyrosequencing (UDPS) to detect minority RAMs.
  
  
  RESULTS
  Bulk genotyping identified NNRTI-resistant RAMs in 3/27 (11%) patients while UDPS identified NNRTI-resistant RAMs in 10/27 (37%) patients. The 11 RAMs not detected by bulk sequencing were A98G (n=2), L100I (n=3), K101E (n=2), V106I (n=3) and E138G (n=1). The prevalence of these minority variants was 0.34-18.26%. The absolute copy numbers of minority resistant variants were 3.21-5.53 log copies/mL. CRF02 harboured more minority resistant variants than subtypes B (P<0.05). Four samples (15%) had a major rilpivirine resistant mutation (E138G, K101E and E138A), 3 of which were detected by UDPS.
  
  
  CONCLUSIONS
  In these primary HIV infected patients, as regards to the detection of RAMs at the cut-off level>15-25% of the virus population, the concordance between bulk genotypic and UDPS was perfect. UDPS detected additional major NNRTI-resistant mutations, including rilpivirine resistant variants. Further studies are needed to assess the impact of these minority variants on treatment efficacy.
authors: CHU Toulouse, Hôpital Purpan, Laboratoire de virologie, Institut fédératif de biologie de Purpan, F-31300, France.
authors: F
authors: F
authors: Nicot
authors: A
authors: A
authors: Saliou
authors: S
authors: S
authors: Raymond
authors: K
authors: K
authors: Sauné
authors: M
authors: M
authors: Dubois
authors: P
authors: P
authors: Massip
authors: B
authors: B
authors: Marchou
authors: P
authors: P
authors: Delobel
authors: J
authors: J
authors: Izopet
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D009570:Nitriles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D000068696:Rilpivirine
chemical_list: D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine