We review the background and key studies that inform decisions on when to initiate antiretroviral therapy (ART) in infants and children. The World Health Organization staging system from 2006 was based on conditions commonly
seen in Africa and provided an impetus for advancing ART in children. Because of poor predictive value of CD4 counts in infancy and inability to predict risk of death or disease progression, we recommend initiating ART in all infants under a year of age. CD4 thresholds for initiating therapy decline as children become older. WHO stage 3 and 4 should trigger ART regardless of CD4 count. Over 5 years of age, a CD4 count <350/μl requires ART.