title: Impact of low-level-viremia on HIV-1 drug-resistance evolution among antiretroviral treated-patients.
abstract: BACKGROUND
  Drug-resistance mutations (DRAM) are frequently selected in patients with virological failure defined as viral load (pVL) above 500 copies/ml (c/mL), but few resistance data are available at low-level viremia (LLV). Our objective was to determine the emergence and evolution of DRAM during LLV in HIV-1-infected patients while receiving antiretroviral therapy (ART).
  
  
  METHODS
  Retrospective analysis of patients presenting a LLV episode defined as pVL between 40 and 500 c/mL on at least 3 occasions during a 6-month period or longer while on the same ART. Resistance genotypic testing was performed at the onset and at the end of LLV period. Emerging DRAM was defined during LLV if never detected on baseline genotype or before.
  
  
  RESULTS
  48 patients including 4 naive and 44 pretreated (median 9 years) presented a LLV episode with a median duration of 11 months. Current ART included 2NRTI (94%), ritonavir-boosted PI (94%), NNRTI (23%), and/or raltegravir (19%). Median pVL during LLV was 134 c/mL. Successful resistance testing at both onset and end of the LLV episode were obtained for 37 patients (77%), among who 11 (30%) acquired at least 1 DRAM during the LLV period: for NRTI in 6, for NNRTI in 1, for PI in 4, and for raltegravir in 2. During the LLV period, number of drugs with genotypic resistance increased from a median of 4.5 to 6 drugs. Duration and pVL level of LLV episode, duration of previous ART, current and nadir CD4 count, number of baseline DRAM and GSS were not identified as predictive factors of resistance acquisition during LLV, probably due to limited number of patients.
  
  
  CONCLUSIONS
  Persistent LLV episodes below 500 c/ml while receiving ART is associated with emerging DRAM for all drug classes and a decreasing in further therapeutic options, suggesting to earlier consider resistance monitoring and ART optimization in this setting.
authors.affiliation: Laboratoire de Virologie, Hôpital Saint Louis-APHP, Paris, France. constance.delaugerre@sls.aphp.fr
authors.forename: Constance
authors.initials: C
authors.lastname: Delaugerre
authors.forename: Sébastien
authors.initials: S
authors.lastname: Gallien
authors.forename: Philippe
authors.initials: P
authors.lastname: Flandre
authors.forename: Dominique
authors.initials: D
authors.lastname: Mathez
authors.forename: Rishma
authors.initials: R
authors.lastname: Amarsy
authors.forename: Samuel
authors.initials: S
authors.lastname: Ferret
authors.forename: Julie
authors.initials: J
authors.lastname: Timsit
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Molina
authors.forename: Pierre
authors.initials: P
authors.lastname: de Truchis
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count / Q000379:methods; D024882:Drug Resistance, Viral / Q000187:drug effects / Q000235:genetics*; D019143:Evolution, Molecular; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000235:genetics*
chemical_list: D044966:Anti-Retroviral Agents