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Published on: November 27, 2019
False-negative HIV-1 polymerase chain reaction in a 15-month-old boy with HIV-1 subtype C infection
Insights
Polymerase chain reaction (PCR) testing for HIV in infants can yield false negatives due to rare mutations. Alternative PCR assays are crucial for accurate diagnosis and timely treatment of pediatric HIV infection.
Area of Science:
- Virology
- Infectious Diseases
- Molecular Diagnostics
Background:
- Polymerase chain reaction (PCR) is the standard for diagnosing HIV in children under 18 months.
- Discordance between clinical symptoms and PCR results necessitates further investigation.
Purpose of the Study:
- To report a case of a false-negative HIV PCR result in an infant.
- To highlight the need for improved PCR assays for diverse HIV subtypes.
Main Methods:
- Case report of a 15-month-old HIV-exposed boy with recurrent infections.
- Utilized routine HIV PCR (Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test) and alternative PCR and viral load assays with different primer sets.
- Performed sequence analysis of Gag sequences.
Main Results:
- Routine HIV PCR tests were negative in the child at multiple time points (6 weeks, 6 months, 7 months, 15 months) and in the mother.
- Alternative PCR and viral load assays detected HIV RNA/proviral DNA in both mother and child.
- Sequence analysis identified HIV-1 subtype C with rare mutations potentially causing primer/probe mismatch in the initial assay.
Conclusions:
- Rare mutations in HIV subtypes can lead to false-negative results with standard PCR assays.
- Development of more reliable PCR assays is needed to detect a broader range of HIV subtypes.
- Accurate and timely diagnosis is essential for initiating antiretroviral therapy and improving outcomes in pediatric HIV.
Abstract:
Polymerase chain reaction (PCR) testing is the gold standard for determining the HIV status in children <18 months of age. However, when clinical manifestations are not consistent with laboratory results, additional investigation is required. We report a 15-month-old HIV-exposed boy referred to our hospital after he had been admitted several times for infectious diseases. A rapid antibody test on the child was positive, while routine diagnostic HIV PCRs using the Roche COBAS Ampliprep/COBAS TaqMan HIV Qual Test were negative at 6 weeks, 6 months, 7 months and 15 months. In addition, the same PCR test performed on the HIV-infected mother was also negative. Alternative PCR and viral load assays using different primer sets detected HIV RNA or proviral DNA in both child and mother. Gag sequences from the child and his mother classified both infections as HIV-1 subtype C, with very rare mutations that may have resulted in PCR assay primer/probe mismatch. Consequently, the child was commenced on antiretroviral therapy and made a remarkable recovery. These findings indicate that more reliable PCR assays capable of detecting a wide range of HIV subtypes are desirable to circumvent the clinical problems created by false-negative PCR results.
