title: Performance of HIV-1 drug resistance testing at low-level viremia and its ability to predict future virologic outcomes and viral evolution in treatment-naive individuals.
abstract: BACKGROUND
  Low-level viremia (LLV; human immunodeficiency virus [HIV-1] RNA 50-999 copies/mL) occurs frequently in patients receiving antiretroviral therapy (ART), but there are few or no data available demonstrating that HIV-1 drug resistance testing at a plasma viral load (pVL) <1000 copies/mL provides potentially clinically useful information. Here, we assess the ability to perform resistance testing by genotyping at LLV and whether it is predictive of future virologic outcomes in patients beginning ART.
  
  
  METHODS
  Resistance testing by genotyping at LLV was attempted on 4915 plasma samples from 2492 patients. A subset of previously ART-naive patients was analyzed who achieved undetectable pVL and subsequently rebounded with LLV (n = 212). A genotypic sensitivity score (GSS) was calculated based on therapy and resistance testing results by genotyping, and stratified according to number of active drugs.
  
  
  RESULTS
  Eighty-eight percent of LLV resistance assays produced useable sequences, with higher success at higher pVL. Overall, 16 of 212 (8%) patients had pretherapy resistance. Thirty-eight of 196 (19%) patients without pretherapy resistance evolved resistance to 1 or more drug classes, primarily the nucleoside reverse transcriptase (14%) and/or nonnucleoside reverse transcriptase (9%) inhibitors. Patients with resistance at LLV (GSS <3) had a 2.1-fold higher risk of virologic failure (95% confidence interval, 1.2- to 3.7-fold) than those without resistance (P = .007). Progressively lower GSS scores at LLV were associated with a higher increase in pVL over time (P < .001). Acquisition of additional resistance mutations to a new class of antiretroviral drugs during LLV was not found in a subset of patients.
  
  
  CONCLUSIONS
  Routine HIV-1 genotyping of LLV samples can be performed with a reasonably high success rate, and the results appear predictive of future virologic outcomes.
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS.
authors.forename: A
authors.initials: A
authors.lastname: Gonzalez-Serna
authors.forename: J E
authors.initials: JE
authors.lastname: Min
authors.forename: C
authors.initials: C
authors.lastname: Woods
authors.forename: D
authors.initials: D
authors.lastname: Chan
authors.forename: V D
authors.initials: VD
authors.lastname: Lima
authors.forename: J S G
authors.initials: JS
authors.lastname: Montaner
authors.forename: P R
authors.initials: PR
authors.lastname: Harrigan
authors.forename: L C
authors.initials: LC
authors.lastname: Swenson
mesh_terms: D000328:Adult; D024882:Drug Resistance, Viral; D019143:Evolution, Molecular; D005260:Female; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods*; D015658:HIV Infections / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011379:Prognosis; D015203:Reproducibility of Results; D016896:Treatment Outcome; D019562:Viral Load
keywords: ART; HIV-1; low-level viremia; outcome; resistance