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False-positive HIV DNA PCR testing of infants: implications in a changing epidemic
Ute Dagmar Feucht1, Brian Forsyth, Mariana Kruger
1Department of Paediatrics, Kalafong Hospital, University of Pretoria, South Africa. ute.feucht@up.ac.za
Insights
False-positive HIV DNA PCR tests in children can impact the paediatric HIV epidemic. Declining transmission rates lower the positive predictive value of these tests, requiring updated diagnostic strategies.
Area of Science:
- Paediatric Infectious Diseases
- Molecular Diagnostics
- Epidemiology
Background:
- False-positive results from HIV DNA PCR tests in children can lead to misdiagnosis.
- Sub-Saharan Africa faces challenges with paediatric HIV diagnosis and treatment.
Purpose of the Study:
- To investigate false-positive HIV DNA PCR test results in children.
- To assess the implications for the paediatric HIV epidemic in sub-Saharan Africa.
Main Methods:
- A 6-year retrospective review of children under 18 months at an HIV treatment site in South Africa.
- Analysis of HIV DNA PCR and quantitative HIV RNA PCR results to confirm infection status.
- Calculation of the influence of changing HIV transmission rates on the predictive values of HIV DNA PCR tests.
Main Results:
- Of 718 children, 40 initially tested positive for HIV DNA PCR but were later confirmed HIV-uninfected (positive predictive value of 94.4%).
- Most uninfected children received PMTCT interventions and were asymptomatic or mildly symptomatic.
- Decreasing HIV transmission rates significantly reduce the positive predictive value of single HIV DNA PCR tests.
Conclusions:
- Declining mother-to-child HIV transmission rates lower the positive predictive value of HIV DNA PCR tests.
- Diagnostic algorithms need adaptation to prevent misdiagnosis and inappropriate treatment in infants.
- Early antiretroviral therapy initiation in asymptomatic infants requires careful consideration of test accuracy.
Aim:
To examine false-positive HIV DNA polymerase chain reaction (PCR) test results in children, and the potential implications for the paediatric HIV epidemic in sub-Saharan Africa.
Methods:
A review was done of records over a 6-year period of children less than 18 months old at an HIV treatment site in South Africa, to evaluate those with an initial 'false'-positive HIV DNA PCR result, but later proven to be HIV-uninfected with HIV DNA PCR and/or quantitative HIV RNA PCR tests. We calculated the influence of changing HIV transmission rates on predictive values (PV) of HIV DNA PCR tests in a hypothetical population of all HIV-exposed infants over a 1-year period. (Positive PV: proportion of individuals with a positive test with disease; negative PV: proportion of individuals with negative test and no disease).
Results:
Of 718 children, 40 with an initial positive HIV DNA PCR test were subsequently proven to be HIV-uninfected, resulting in a positive PV of 94.4%. Most (75%) uninfected children had PMTCT interventions and were asymptomatic or mildly symptomatic (77.5%). Calculations using a test specificity of 99.4%, as reported previously, show a decrease in positive PV using a single-test strategy from 98.6% at 30% HIV transmission rate, to 94.8% at 10% transmission, to 62.5% at 1% transmission. Reduction in test specificity further decreases positive PV at low transmission rates.
Conclusion:
Decreasing mother-to-child HIV transmission rates reduce the positive predictive value of a single HIV DNA PCR test result, necessitating adaptations to diagnostic algorithms to avoid misdiagnosis and inappropriate treatment, especially with early initiation of antiretroviral therapy in asymptomatic infants.
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