Despite 95% coverage via the prevention-of-mother-to-child-transmission (PMTCT) programme, 14 000 children in South Africa became HIV-infected in 2012. There are many reasons for this gap in PMTCT efforts. Late maternal diagnosis of HIV, late antenatal antiretroviral therapy (ART) initiation, seroconversion in pregnancy, and inadequate adherence to ART during gestation singly and collectively increase the risk of transmission. Early initiation of ART in the first few weeks of life significantly reduces the HIV-associated morbidity and mortality in HIV-infected infants, compared with deferred initiation and may reduce the latent HIV-1 reservoir in children. Furthermore, a recent South African study documents that 76% of babies who would have tested HIV positive via polymerase chain reaction (PCR) by 6 weeks could have been diagnosed at birth. Therefore, the Western Cape Province (WCP) Department of Health adopted new guidelines in June 2014 (and the South African Department of Health in December 2014) to test ’high-risk’ infants at birth. Infants testing PCR-positive are started on ART as soon as possible.