title: Systematic review of the use of dried blood spots for monitoring HIV viral load and for early infant diagnosis.
abstract: BACKGROUND
  Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.
  
  
  RESULTS
  Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52-100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78-100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies.
  
  
  CONCLUSIONS
  Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation.
  
  
  BACKGROUND
  PROSPERO Registration #: CRD42013003621.
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Smit
authors.affiliation: Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Sollis
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, 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: Joseph H
authors.initials: JH
authors.lastname: Perriens
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: D059788:Dried Blood Spot Testing / Q000379:methods*; D042241:Early Diagnosis; D015658:HIV Infections / Q000097:blood / Q000175:diagnosis* / Q000821:virology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007223:Infant; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019562:Viral Load