POLYMERASE CHAIN-REACTION FOR THE DIAGNOSIS OF HIV-INFECTION IN ADULTS - A METAANALYSIS WITH RECOMMENDATIONS FOR CLINICAL-PRACTICE AND STUDY DESIGN

Purpose: To do a meta-analysis of studies that have evaluated the sens itivity and specificity of polymerase chain reaction (PCR) assay for t he diagnosis of human immunodeficiency virus (HIV) infection in adults . Evaluating the performance of PCR is difficult because in certain cl inical situations, the sensitivity or specificity of PCR may exceed th ose of the current reference standard tests (enzyme immunoassay follow ed by confirmatory Western blot analysis). Therefore, an additional go al was to develop recommendations for 1) the design of future evaluati ve studies of PCR and 2) the use of PCR in persons with suspected HIV infection. Data Sources: Studies published between 1988 and 1994 that were identified in a search of 17 computer databases, including MEDLIN E, and abstracts identified from conference proceedings. Study Selecti on: Studies were included if DNA amplification by PCR was done on peri pheral blood mononuclear cells from adults. Ninety-six studies met the inclusion criteria. Data Extraction: Data were extracted independentl y by two reviewers. Study design was assessed independently by two inv estigators blinded to study results. Results: Reported sensitivities f or PCR range from 10% to 100%, and specificities range from 40% to 100 %. A summary receiver-operating characteristic curve based on all 96 s tudies has a maximum joint sensitivity and specificity (upper left poi nt on the curve, where sensitivity equals specificity) of 97.0% to 98. 1%. If the threshold value that defines a positive PCR result is chose n so that sensitivity is higher than 98.1%, specificity will decrease to less than 98.1%. Conversely, if the threshold value that defines a positive PCR result is chosen so that specificity is greater than 98.1 %, sensitivity will decrease to less than 98.1%. If sensitivity and sp ecificity are chosen to be equal, the corresponding false-positive rat e is 1.9% to 3.0%. At the maximum joint sensitivity and specificity, t he positive predictive value of PCR ranges from 34% to 85% as the prev alence of HIV increases from 1.0% to 10%. We identified seven areas in which study design could be modified to 1) reduce susceptibility to b ias in estimates of the sensitivity and specificity of PCR and 2) to i ncrease the generalizability of the study results. These modifications will also help to overcome methodologic problems created by the lack of a reference standard test. Conclusions: The PCR assay is not suffic iently accurate to be used for the diagnosis of HIV infection without confirmation. Use of PCR for the diagnosis of HIV in adults should be limited to situations in which antibody tests are known to be insuffic ient. Future studies of PCR performance should be sufficiently large a nd should use adequate reference standard tests and standardized metho ds for the performance of PCR. Specimens should be evaluated by person s blinded to clinical status and to the results of other diagnostic te sts for HIV infection.