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Loss of detectability and indeterminate results: Challenges facing HIV infant diagnosis in South Africa’s expanding ART programme


AF Haeri Mazanderani
NM du Plessis
WN Thomas
E Venter
T Avenant

Abstract

Background. Early infant diagnosis with rapid access to treatment has been found to reduce HIV-associated infant mortality and morbidity considerably. In line with international standards, current South African guidelines advocate routine HIV-1 polymerase chain reaction (PCR) testing at 6 weeks of age for all HIV-exposed infants and ‘fast-track’ entry into the HIV treatment programme for those who test positive. Importantly, testing occurs within the context of increasing efforts at prevention of mother-to-child transmission (PMTCT) by means of maternal and infant  antiretroviral therapy (ART). In addition, infants already initiated on combination ART (cART) may be retested with PCR assays for ‘confirmatory’ purposes, including assessment prior to adoption. The potential for cART to  compromise the sensitivity of HIV-1 PCR assays has been described, although there are limited and conflicting data regarding the effect of PMTCT regimens on HIV-1 PCR diagnostic sensitivity.
Methods. We describe a case series of three infants with different ART exposures in whom HIV diagnosis,  confirmation or the result of retesting for adoption purposes were uncertain.
Results. These cases demonstrate that ART can be associated with a loss of detectability of HIV, leading to ‘false-negative’ HIV-1 PCR results in infants on cART. Furthermore, current PMTCT practices may lead to repeatedly  indeterminate results with a subsequent delay in initiation of cART.
Conclusion. The sensitivity of HIV-1 PCR assays needs to be re-evaluated within the context of different ART exposures, and diagnostic algorithms should be reviewed accordingly.

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eISSN: 2078-5135
print ISSN: 0256-9574