We compared the response to protease inhibitor-containing highly active antiretroviral therapy in 175 HIV-1 treatment-naive patients harbouring subtype B versus non-B. No difference in the proportion of patients with viral loads below 400 copies/ml was observed at month 24. However, there was a significant difference in the median CD4 cell increase at month 24. Whether this is caused by viral or immune factors warrants further investigation.