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While there is ample evidence that antiretroviral therapy (ART) can improve cognitive outcomes in older children living with HIV, encephalopathy in infants has historically been considered an advanced disease presentation with less likelihood of neurodevelopmental recovery on treatment. More recent studies suggest that timely ART can halt encephalopathic disease progression and even lead to symptom resolution. Here we present a case of an HIV-positive infant diagnosed with encephalopathy who experienced impressive and rapid improvement with a multi-disciplinary care approach that included physical and occupational therapy and ART.