Abstract
Early diagnosis of HIV infection among infants and children is critical as prompt initiation of antiretroviral therapy prevents morbidity and death. Yet despite advances in the accuracy and availability of infant HIV diagnostic testing, there are increasing challenges with making an early definitive diagnosis. These challenges relate primarily to advances in prevention of mother-to-child transmission (PMTCT) of HIV. Although PMTCT programs have proven to be highly effective in reducing infant HIV infection, infants who are HIV-infected may achieve virological suppression and loss of detectability of HIV nucleic acid prior to diagnosis because of antiretroviral drug exposure. Hence, false-negative and indeterminate HIV polymerase chain reaction (PCR) results can occur, especially among high-risk infants given multi-drug prophylactic regimens. However, the infant HIV diagnostic landscape is also complicated by the inevitable decline in the positive predictive value of early infant diagnosis (EID) assays. As PMTCT programs successfully reduce the mother-to-child transmission rate, the proportion of false-positive EID results will increase. Consequently, false-negative and false-positive HIV PCR results are increasingly likely despite highly accurate diagnostic assays. The problem is compounded by the seemingly intractable prevalence of maternal HIV within some settings, resulting in a considerable absolute burden of HIV-infected infants despite a low mother-to-child transmission rate.
Highlights
Diagnosis of HIV infection among infants and young children is critical as prompt initiation of antiretroviral therapy (ART) markedly reduces morbidity and mortality[1]
As a result of the passive transfer of maternal HIV antibodies to infants in the third trimester and the persistence of these antibodies during infancy and early childhood, HIV antibody tests used to diagnose HIV in older children and adults cannot be used for early infant diagnosis (EID)
The World Health Organization (WHO) recommends repeat HIV testing for all infants 3 months after breastfeeding cessation - if the infant/ child is less than 18 months of age at weaning polymerase chain reaction (PCR) testing is recommended, whereas if the child is more than 18 months of age antibody testing is recommended[24]
Summary
Diagnosis of HIV infection among infants and young children is critical as prompt initiation of antiretroviral therapy (ART) markedly reduces morbidity and mortality[1]. Studies suggest that infant prophylactic regimens can result in virological suppression and loss of detectability by PCR assays in HIV-infected infants[15,16,17,18] For these reasons, guidelines from the US recommend that infants at high risk of HIV transmission undergo repeat nucleic acid testing 2 to 4 weeks after cessation of antiretroviral prophylaxis[19]. The distinction between intrauterine, intrapartum, and postnatal transmission has always been fairly crude but the boundaries have been further blurred by ART exposure as evidenced by case descriptions of infants who test HIV PCR indeterminate at birth followed by negative results and subsequent viral rebound after weaning, suggesting either suppressed intrauterine infection or postnatal transmission[40]. The introduction of ART with even higher viral suppressive properties will require a complete rethink of efficient diagnostic algorithms, paired with more sensitive assays, for HIV diagnosis of infants and children in the future
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