Mother-to-child transmission accounts for the majority of new HIV infections among children worldwide. Post-natal prophylaxis, in addition to other preventive measures, have been very successful in reducing transmission to babies born to mothers living with HIV infection to <2%. Single-drug prophylaxis with zidovudine is the mainstay regimen for infants in low-risk transmission settings. The optimal regimen for newborns of women with anti-retroviral (ARV)-resistant HIV is unknown. We report a baby born to a young mother living with highly resistant perinatally-acquired HIV at a tertiary care centre in Sydney, Australia, in 2018. Furthermore, the challenges with giving postnatal ARV prophylaxis to her baby, in light of the lack of dosing and safety data for many antiretroviral agents for neonates, is discussed. The baby received a combination of lamivudine and raltegravir for a total of six weeks and he was not breast-fed. He had negative HIV proviral DNA polymerase chain reaction at six weeks and three months and a negative HIV serology at 18 months of age.