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

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      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.

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      Most cited references 17

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      National Antiretroviral Treatment Guidelines

      (2004)
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        Emergence of a peak in early infant mortality due to HIV/AIDS in South Africa.

        South Africa has among the highest levels of HIV prevalence in the world. Our objectives are to describe the distribution of South African infant and child mortality by age at fine resolution, to identify any trends over recent time and to examine these trends for HIV-associated and non HIV-associated causes of mortality. A retrospective review of vital registration data was conducted. All registered postneonatal deaths under 1 year of age in South Africa for the period 1997-2002 were analysed by age in months using a generalized linear model with a log link and Poisson family. Postneonatal mortality increased each year over the period 1997-2002. A peak in HIV-related deaths was observed, centred at 2-3 months of age, rising monotonically over time. We interpret the peak in mortality at 2-3 months as an indicator for paediatric AIDS in a South African population with high HIV prevalence and where other causes of death are not sufficiently high to mask HIV effects. Intrauterine and intrapartum infection may contribute to this peak. It is potentially a useful surveillance tool, not requiring an exact cause of death. The findings also illustrate the need for early treatment of mother and child in settings with very high HIV prevalence.
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          Dried blood spots improve access to HIV diagnosis and care for infants in low-resource settings.

          Effective health care delivery to the majority of perinatally exposed infants worldwide, including those enrolled in prevention of mother-to-child transmission programs, is hampered by lack of access to an HIV diagnosis in infancy. Dried blood spot collection from young infants for centralized HIV polymerase chain reaction (PCR) testing is attainable in low-resource settings, provided PCR methodology suitable for routine laboratory service is available. The accuracy of the Roche Amplicor HIV-1 DNA test version 1.5 (Branchburg, NJ) performed on dried blood spots collected prospectively on ordinary Whatman filter paper from a cohort of 300 6-week-old infants born to HIV-infected women in Johannesburg, South Africa, was assessed. Anonymous analysis of the blood spots using a unique DNA extraction procedure was performed in a routine diagnostic laboratory and the results compared with HIV DNA and RNA PCR liquid blood tests at age 6 weeks, and the HIV status of the infant. Dried blood spots were available for 288 infants (96%) of whom 25 (8.7%) were HIV infected. The Roche Amplicor assay yielded a sensitivity of 100% and a specificity of 99.6%. HIV DNA PCR tests on dried blood spots have the potential to improve health care delivery to HIV-affected children in low-resource settings right now.
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            Author and article information

            Affiliations
            [1 ] Kalafong Hospital
            [2 ] Yale University USA
            [3 ] Universiteit Stellenbosch South Africa
            Contributors
            Role: ND
            Role: ND
            Role: ND
            Journal
            samj
            SAMJ: South African Medical Journal
            SAMJ, S. Afr. med. j.
            Health and Medical Publishing Group (Cape Town )
            2078-5135
            March 2012
            : 102
            : 3
            : 149-152
            S0256-95742012000300025

            http://creativecommons.org/licenses/by/4.0/

            Product
            Product Information: SciELO South Africa
            Categories
            Health Care Sciences & Services
            Health Policy & Services
            Medical Ethics
            Medicine, General & Internal
            Medicine, Legal
            Medicine, Research & Experimental

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