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False-positive HIV DNA PCR testing of infants: Implications in a changing epidemic
Abstract
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.
(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.