title: Systematic review of the performance of HIV viral load technologies on plasma samples.
abstract: BACKGROUND
  Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring.
  
  
  RESULTS
  A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1%) and 5.44% (range 1.17-30.00%) across the range of VL counts (2log10-7log10).
  
  
  CONCLUSIONS
  This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL. Prospero registration # CD42013003603.
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Sollis
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Smit
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina, Chapel Hill, North Carolina, United States of America.
authors.forename: Susan
authors.initials: S
authors.lastname: Fiscus
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Nathan
authors.initials: N
authors.lastname: Ford
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Vitoria
authors.affiliation: HIV, Medicine and Science, Clinton Health Access Initiative, New York, New York, United States of America.
authors.forename: Shaffiq
authors.initials: S
authors.lastname: Essajee
authors.affiliation: Department of Haematology, United Kingdom National External Quality Assessment Service (UK NEQAS) for Leucocyte Immunophenotyping, Sheffield, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Barnett
authors.affiliation: Department of Technology and Innovation, Pangaea Global AIDS Foundation, San Fransisco, California, United States of America.
authors.forename: Ben
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Crowe
authors.affiliation: Department of Medicine, Duke Human Vaccine Institute and Center for HIV/AIDS Vaccine Immunology, Durham, North Carolina, United States of America.
authors.forename: Thomas
authors.initials: T
authors.lastname: Denny
authors.affiliation: Department of Immunology- Microbiology, Rush University Medical Center, Chicago, Illinois, United States of America.
authors.forename: Alan
authors.initials: A
authors.lastname: Landay
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Wendy
authors.initials: W
authors.lastname: Stevens
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Habiyambere
authors.affiliation: Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
authors.forename: Jos
authors.initials: J
authors.lastname: Perrins
authors.affiliation: Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Rosanna W
authors.initials: RW
authors.lastname: Peeling
mesh_terms: D000465:Algorithms; D003906:Developing Countries; D015658:HIV Infections / Q000097:blood* / Q000821:virology*; D006679:HIV Seropositivity / Q000821:virology; D015497:HIV-1 / Q000145:classification; D006801:Humans; D025202:Molecular Diagnostic Techniques / Q000379:methods; D010949:Plasma / Q000821:virology*; D016133:Polymerase Chain Reaction; D011933:Reagent Kits, Diagnostic / Q000821:virology; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012698:Serologic Tests; D019562:Viral Load; D014944:World Health Organization
chemical_list: D011933:Reagent Kits, Diagnostic