The CHER trial investigated the impact of early versus deferred antiretroviral therapy (ART) in HIV-infected infants. Infants aged 6-12 weeks with a CD4 percentage of 25% or more were randomly assigned to either early ART (initiated at 1 or 2 years) or deferred ART (initiated when CD4 percentage dropped below 20% or clinical criteria were met). At a median follow-up of 40 weeks, 66% of deferred-therapy infants received ART, while 252 early-therapy infants received ART. Early ART significantly reduced mortality (16% vs. 4%) and disease progression (25% vs. 6%) compared to deferred ART. The hazard ratio for death was 0.24 (95% CI 0.11-0.51), and for disease progression, 0.25 (95% CI 0.15-0.41). Early ART reduced early infant mortality by 76% and HIV progression by 75%. Despite the high CD4 percentage at baseline, most deaths occurred within 6 months of randomization, often due to rapid disease progression or severe infections like pneumonia and gastroenteritis. Early ART was associated with better outcomes, including lower mortality and reduced disease progression. The study highlights the importance of early diagnosis and treatment in HIV-infected infants. The results support the initiation of ART as soon as possible to reduce mortality and progression, even in infants with high CD4 percentages. The trial was conducted in South Africa and involved collaboration with multiple institutions. The findings have significant implications for HIV management in infants, emphasizing the need for early intervention.The CHER trial investigated the impact of early versus deferred antiretroviral therapy (ART) in HIV-infected infants. Infants aged 6-12 weeks with a CD4 percentage of 25% or more were randomly assigned to either early ART (initiated at 1 or 2 years) or deferred ART (initiated when CD4 percentage dropped below 20% or clinical criteria were met). At a median follow-up of 40 weeks, 66% of deferred-therapy infants received ART, while 252 early-therapy infants received ART. Early ART significantly reduced mortality (16% vs. 4%) and disease progression (25% vs. 6%) compared to deferred ART. The hazard ratio for death was 0.24 (95% CI 0.11-0.51), and for disease progression, 0.25 (95% CI 0.15-0.41). Early ART reduced early infant mortality by 76% and HIV progression by 75%. Despite the high CD4 percentage at baseline, most deaths occurred within 6 months of randomization, often due to rapid disease progression or severe infections like pneumonia and gastroenteritis. Early ART was associated with better outcomes, including lower mortality and reduced disease progression. The study highlights the importance of early diagnosis and treatment in HIV-infected infants. The results support the initiation of ART as soon as possible to reduce mortality and progression, even in infants with high CD4 percentages. The trial was conducted in South Africa and involved collaboration with multiple institutions. The findings have significant implications for HIV management in infants, emphasizing the need for early intervention.