title: Evaluation of a Rapid Point of Care Test for Detecting Acute and Established HIV Infection, and Examining the Role of Study Quality on Diagnostic Accuracy: A Bayesian Meta-Analysis.
abstract: BACKGROUND
  Fourth generation (Ag/Ab combination) point of care HIV tests like the FDA-approved Determine HIV1/2 Ag/Ab Combo test offer the promise of timely detection of acute HIV infection, relevant in the context of HIV control. However, a synthesis of their performance has not yet been done. In this meta-analysis we not only assessed device performance but also evaluated the role of study quality on diagnostic accuracy.
  
  
  METHODS
  Two independent reviewers searched seven databases, including conferences and bibliographies, and independently extracted data from 17 studies. Study quality was assessed with QUADAS-2. Data on sensitivity and specificity (overall, antigen, and antibody) were pooled using a Bayesian hierarchical random effects meta-analysis model. Subgroups were analyzed by blood samples (serum/plasma vs. whole blood) and study designs (case-control vs. cross-sectional).
  
  
  RESULTS
  The overall specificity of the Determine Combo test was 99.1%, 95% credible interval (CrI) [97.3-99.8]. The overall pooled sensitivity for the device was at 88.5%, 95% [80.1-93.4]. When the components of the test were analyzed separately, the pooled specificities were 99.7%, 95% CrI [96.8-100] and 99.6%, 95% CrI [99.0-99.8], for the antigen and antibody components, respectively. Pooled sensitivity of the antibody component was 97.3%, 95% CrI [60.7-99.9], and pooled sensitivity for the antigen component was found to be 12.3%, 95% (CrI) [1.1-44.2]. No significant differences were found between subgroups by blood sample or study design. However, it was noted that many studies restricted their study sample to p24 antigen or RNA positive specimens, which may have led to underestimation of overall test performance. Detection bias, selection (spectrum) bias, incorporation bias, and verification bias impaired study quality.
  
  
  CONCLUSIONS
  Although the specificity of all test components was high, antigenic sensitivity will merit from an improvement. Besides the accuracy of the device itself, study quality, also impacts the performance of the test. These factors must be kept in mind in future evaluations of an improved device, relevant for global scale up and implementation.
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
authors.forename: Megan
authors.initials: M
authors.lastname: Smallwood
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Rohit
authors.initials: R
authors.lastname: Vijh
authors.affiliation: Medical Library, Royal Victoria Hospital, McGill University Health Centre, Montreal, Canada.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Nauche
authors.affiliation: Chronic Viral Illness Service, Research Institute of the McGill University Health Centre, Montreal, Canada.|Department of Family Medicine, McGill University, Montreal, Canada.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Lebouché
authors.affiliation: Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.|Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Joseph
authors.affiliation: Division of Clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.|Department of Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Nitika
authors.initials: N
authors.lastname: Pant Pai
mesh_terms: D001499:Bayes Theorem; D015658:HIV Infections / Q000175:diagnosis*; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000175:diagnosis; D006801:Humans; D000067716:Point-of-Care Testing; D011785:Quality Assurance, Health Care; D012680:Sensitivity and Specificity