False-Positive HIV Test Results in Infancy and Management of Uninfected Children Receiving Antiretroviral Therapy

Abstract

This report summarizes 2 children misdiagnosed with HIV infection in a clinic in rural Zambia and discusses the implications of false-positive HIV DNA tests in HIV-exposed infants, including the potential magnitude of the problem. Recommendations are needed to address the management of children receiving antiretroviral therapy who are suspected of being uninfected.

Prevalence and outcomes of HIV‐1 diagnostic challenges during universal birth testing – an urban South African observational cohort

“…All three of these infants have since followed up on site, and treatment has been interrupted under close clinical supervision. The diagnosis of these infants remains uncertain as it has yet to be determined what the required length of time is for monitoring post-treatment cessation in order to exclude HIV-1 infection [24]. Case e represents the only infant with an uncertain HIV-1 status where combination ART has not been stopped and is also the only case, amongst those with an uncertain diagnosis, that tested HIV-1 PCR positive at birth.…”

“…Waning antibody levels and seroreversion following early ART initiation are additional phenomena that make later diagnostic confirmation difficult [20][21][22]. In contrast to the possibility of loss of detectability, there is also concern that on account of the dramatic reduction in motherto-child transmission in South Africa there will necessarily be a drop in the positive predictive value of all infant diagnostic testing methodologies, thereby increasing the risk of treating uninfected infants [23][24][25].…”

Evaluation of four commercial virological assays for early infant HIV-1 diagnosis using dried blood specimens

“…Indeterminate results during EID using CVAs are a significant challenge for HIV diagnostic services. False-positive results by CVAs were previously reported in other African countries (29,(33)(34)(35)(36)(37)(38)(39). In South Africa, 40 (5.6%) of 718 infants who initially tested HIV positive using Amplicor HIV-1 DNA v1.5 Test or Roche-dx-v1 were not infected after using serological testing in confirmatory specimens (28).…”

“…A low rate of false positive and negative diagnoses should be expected when using CVAs for EID, and they are affected by HIV-1 vertical transmission rate. As mother-to-child transmission and the prevalence of HIV infection among HIVexposed infants decreases, the number of false-positive results using CVAs will increase and the positive predicted value will decrease if the test specificity is not 100% (28,29). Thus, as the incidence of perinatal HIV infection decreases, the number of false-positive HIV tests increases.…”

“…In South Africa, 40 (5.6%) of 718 infants who initially tested HIV positive using Amplicor HIV-1 DNA v1.5 Test or Roche-dx-v1 were not infected after using serological testing in confirmatory specimens (28). In Zambia, false-positive results using CVA were also reported in two infants (29). In the Kenyan EID Program, indeterminate results were more often negative than positive (35).…”