Introduction HIV is a highly diverse virus with significant genetic variability which may confer biologic differences that could impact on treatment outcomes. Materials and methods We studied the association between HIV subtypes and immunologic and virologic outcomes in a longitudinal cohort of 169 patients on combination antiretroviral therapy. Participants were followed up for 5 years. Demographic data, CD4 cell count and viral loads (VL) were extracted from medical records. Whole protease gene and codon 1–300 of the reverse transcriptase gene were sequenced and analysed. Results Sixty-four percent of participants were females with a median age of 35 years. Twelve different subtypes were observed, the commonest being CRF 02_AG (55.0%) and subtypes G (23.1%). All subtypes showed steady rise in CD4 count and there was no difference in proportion who achieved CD4+ cell count rise of ≥100 cells/μL from baseline within 12 months’ post-initiation of ART, or ≥350 cells/μL at 60 months’ post-initiation. Median time to attaining a rise of ≥350 cells/μL was 24 months (6–48 months). The proportion that achieved undetectable VL at month 6 and 12 post-initiation of ART were comparable across subtypes. At end of 5th year, there was no statistical difference in proportion with virologic failure. Conclusion No association between HIV subtypes and immunologic or virologic response to therapy was observed, suggesting that current first-line ART may have similar efficacy across subtype predominating in South-West Nigeria.