Evolving complexities of infant HIV diagnosis within Prevention of Mother-to-Child Transmission programs [version 1; peer review: 2 approved]

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.