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.