With 88% of HIV-1–infected individuals living in areas of high prevalence of non–B subtypes and with expanded global access to antiretroviral treatment (ART), studying disease progression amongst non–B subtypes gains relevance. Optimized clinical management is a possibility with knowledge of non–B subtype profiles at baseline, which is currently not possible due to lack of subtype-specific point-of-care assays. In a systematic review, we synthesized global evidence on differential disease progression amongst non–B subtypes in ART-naive individuals. Due to lack of consistent effect measures, we avoided pooling data and inferred patterns with respect to disease progression outcomes (ie, AIDS, Death, CD4, viral load changes). Subtypes C and D were more aggressive, followed by G, AE, and AG, and A being the least aggressive of all HIV-1 subtypes. Evidence of greater rates of disease progression in globally prevalent C and D subtypes highlight the importance of expanding early HIV detection, and determining subtype profile at baseline with CD4 staging to optimize the quality of ART delivery and care in global settings.