Coinfection of HIV-1 and cytomegalovirus (CMV) may occur given the shared routes of transmission, and the clinical presentations of each process overlap. We present a case of acute HIV-1 and CMV coinfection presenting with an acute febrile illness complicated by meningitis, hepatitis, and retinopathy. This and other similar cases demonstrate the need to consider CMV coinfection in acute HIV-1 disease, particularly in situations with significant end-organ damage.