title: Pre-treatment minority HIV-1 drug resistance mutations and long term virological outcomes: is prediction possible?
abstract: Although the use of highly active antiretroviral therapy in HIV positive individuals has proved to be effective in suppressing the virus to below detection limits of commonly used assays, virological failure associated with drug resistance is still a major challenge in some settings. The prevalence and effect of pre-treatment resistance associated variants on virological outcomes may also be underestimated because of reliance on conventional population sequencing data which excludes minority species. We investigated long term virological outcomes and the prevalence and pattern of pre-treatment minority drug resistance mutations in individuals initiating HAART at a local HIV clinic.
  
  
  
  Patient's records of viral load results and CD4 cell counts from routine treatment monitoring were used and additional pre-treatment blood samples for Sanger sequencing were obtained. A selection of pre-treatment samples from individuals who experienced virological failure were evaluated for minority resistance associated mutations to 1 % prevalence and compared to individuals who achieved viral suppression.
  
  
  
  At least one viral load result after 6 months or more of treatment was available for 65 out of 78 individuals followed for up to 33 months. Twenty (30.8 %) of the 65 individuals had detectable viremia and eight (12.3 %) of them had virological failure (viral load > 1000 RNA copies/ml) after at least 6 months of HAART. Viral suppression, achieved by month 8 to month 13, was followed by low level viremia in 10.8 % of patients and virological failure in one patient after month 20. There was potentially reduced activity to Emtricitabine or Tenofovir in three out of the eight cases in which minority drug resistance associated variants were investigated but detectable viremia occurred in one of these cases while the activity of Efavirenz was generally reduced in all the eight cases.
  
  
  
  Early viral suppression was followed by low level viremia for some patients which may be an indication of failure to sustain viral suppression over time. The low level viremia may also be representing early stages of resistance development. The mutation patterns detected in the minority variants showed potential reduced drug sensitivity which highlights their potential to dominate after treatment initiation.
  
  
  
  Not applicable.
authors.affiliation: Department of Medical Virology, University of Pretoria, Pretoria, South Africa. mayibongwe.mzingwane@nust.ac.zw.|Department of Pathology, National University of Science & Technology, Faculty of Medicine, P. O Box AC939, Ascot, Bulawayo, Zimbabwe. mayibongwe.mzingwane@nust.ac.zw.
authors.forename: M L
authors.initials: ML
authors.lastname: Mzingwane
authors.affiliation: Centre for HIV and Sexually Transmitted Infections, National Institute of communicable Diseases, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: C T
authors.initials: CT
authors.lastname: Tiemessen
authors.affiliation: Department of Medical Virology, University of Pretoria, Pretoria, South Africa.|National Health Laboratory Services Tswane Academic Division, Pretoria, South Africa.
authors.forename: K L
authors.initials: KL
authors.lastname: Richter
authors.affiliation: Department of Medical Virology, University of Pretoria, Pretoria, South Africa.|National Health Laboratory Services Tswane Academic Division, Pretoria, South Africa.
authors.forename: S H
authors.initials: SH
authors.lastname: Mayaphi
authors.affiliation: Centre for HIV and Sexually Transmitted Infections, National Institute of communicable Diseases, Johannesburg, South Africa.
authors.forename: G
authors.initials: G
authors.lastname: Hunt
authors.affiliation: Department of Medical Virology, University of Pretoria, Pretoria, South Africa.|National Health Laboratory Services Tswane Academic Division, Pretoria, South Africa.
authors.forename: S M
authors.initials: SM
authors.lastname: Bowyer
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D015995:Prevalence; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: Drug resistance; HIV; Minority variants; Virological outcomes