Positive Predictive Value (PPV) of Tests

“Even with tests as accurate (>99% sensitive and >99% specific) as the current third-generation HIV enzyme-linked immunosorbent assay (ELISA) coupled with Western blot or other confirmatory tests, an increasing number of false-positive results may be anticipated when large numbers of persons at low risk are tested.”

“Screening tests are ubiquitous in contemporary practice, yet the principles of screening are widely misunderstood. Screening is the testing of apparently well people to find those at increased risk of having a disease or disorder. Although an earlier diagnosis generally has intuitive appeal, earlier might not always be better, or worth the cost. Four terms describe the validity of a screening test: sensitivity, specificity, and predictive value of positive and negative results. For tests with continuous variables--eg, blood glucose--sensitivity and specificity are inversely related; where the cutoff for abnormal is placed should indicate the clinical effect of wrong results. The prevalence of disease in a population affects screening test performance: in low-prevalence settings, even very good tests have poor predictive value positives…inappropriate application or interpretation of screening tests can rob people of their perceived health, initiate harmful diagnostic testing, and squander health-care resources.”

“The positive predictive value of a single [rapid HIV] test (i.e., the probability that a positive test represents true infection) will be low among populations with low prevalence. Therefore, a reactive rapid test must be confirmed by a supplemental test (e.g., Western blot). However, necessary peripartum [at around the time of birth] interventions to reduce the risk for perinatal transmission might need to be based on the preliminary results of rapid testing at labor and delivery [i.e. it’s okay to give toxic antiviral drugs to babies that are uninfected]”

“The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response. Differences in outcome were significant when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses”

“As the number of women being screened has increased, the proportion of false-positive and ambiguous (indeterminate) test results has increased and the positive predictive value (PPV) of the standard HIV test has decreased”

“using the CDC estimate that 0.6% of Americans are HIV-positive, in a population of 10,000 [with a 99% accurate HIV test combination] 60 Americans would test positive! This 60 must include all the false positives, 30, leaving only 30 people actually infected. This leads to the following conclusion: using a 99% accuracy, one finds as many false positives as true positives.”

“Former Senator Lawton Chiles of Florida reported at an AIDS conference in 1987 that of 22 blood donors in Florida who were notified that they tested HIV-positive with the ELISA test, seven committed suicide. In the same medical text that reported this tragedy, the reader is informed that 'even if the results of both AIDS tests, the ELISA and WB (Western blot), are positive, the chances are only 50:50 that the individual is infected'…An estimated PPV [Positive Predictive Value, the probability that a positive test is a true positive] of about 50% for heterosexual men who do not engage in risky behaviour is consistent with the report of the Enquete Committee of the German Bundestag, which estimated the PPV for low-risk people as `less than 50%’”

“The predictive value of a positive test is strongly influenced by the prevalence of HIV-1 infection in the population tested. For example, in low prevalence populations the predictive value was 11.1% (1/9) while in populations with known HIV-1 infection, the predictive value was 97.1% (395/407).”

“In low risk populations, where the rate of HIV-1 infection may not exceed 0.1%, the rate of antigen positivity could be as low as 0.01%. Assuming a test sensitivity of 100%, the positive predictive value of a repeatedly reactive test would be only 5.9%, i.e. only 6 tests per 100 would be true positives.”

“the predictive value of the ELISA screening test is dependent on the prevalence of infection in the population test. Given the low prevalence of HIV infection in the United States, it is estimated that approximately one in 200 persons is infected; a specificity of 99% will yield ~100 false results per 10,000 individuals tested, for every 25 infected individuals identified.”

“Most patients (68 to 89%) from low risk groups (prevalence of 0.1% or less) who show reactivity on screening tests will have false-positive results…The predictive value of a positive ELISA varies from 2% to 99%”

“Although confirmatory testing greatly increases specificity, there may still be false-positive findings when screening populations with a low prevalence of HIV infection”

“the likelihood that a reactive test means previous exposure to HTLV-III [HIV] is low in the blood donor population. It has been estimated, for example, that for a test with 95% sensitivity and specificity, the predictive value ...of a positive test will be only 2%”

“when the EIA is used to screen populations in which the prevalence of infection with HIV-1 is low (e.g., blood donors), nonspecific reactions may be more common…AIDS and AIDS-related conditions are clinical syndromes and their diagnosis can only be established clinically. Testing alone cannot be used to diagnose AIDS even if the recommended investigation of reactive specimens suggests a high probability that antibodies to HIV-1 are present…The risk of an asymptomatic person with a repeatedly reactive serum developing AIDS or an AIDS-related condition is not known”

“nonspecific results [on antibody tests] are found commonly when screening tests are used in large populations…the psychosocial and medical implications of a positive antibody test may be devastating”