The objective of this review was to examine different monitoring strategies (clinical, immunologic (CD4 T cell count measurement) and virologic (viral load measurement)) to inform revision of the 2013 WHO guidelines for antiretroviral therapy (ART) in low and middle-income countries.A systematic review.We searched 10 databases, reference lists of included research studies and contacted experts in an attempt to identify all relevant studies regardless of language or publication status. We included both randomized controlled trials (RCTs) and observational studies. We selected studies that examined routine clinical monitoring (CM), immunologic monitoring (IM) or virologic monitoring (VM). CM involved clinical evaluation and basic laboratory blood testing without CD4 T cell count or viral load. Two authors independently assessed study eligibility, extracted data and graded methodological quality.A total of six studies were identified, including five RCTs and one observational study. Two RCTs among adults found an increased risk of AIDS-defining illness and mortality in CM compared to CM + IM. Two studies compared CM + IM to CM + IM + VM, with one finding a mortality advantage in the CM + IM + VM group. Duration of viremia and time to switching to a second-line regimen were longer in CM + IM compared to CM + IM + VM. Only one trial was conducted in children, and showed no difference in mortality comparing CM and CM+IM. No studies specifically studied pregnant women.CM + IM was shown to be beneficial in terms of a combined mortality and morbidity endpoint compared to CM alone. VM was associated with shorter duration of viremia and higher rates of switching, but an impact on mortality was not consistently shown. Pooled outcome estimates were possible with comparison of only CM to CM + IM. Further HIV research on different VL monitoring strategies is required. These data support the recommendation in the 2013 WHO ART guidelines for the use of VM to confirm and diagnose ART failure, and for the use of IM + CM when VM is not available.