HIV viral load (VL) is an important predictor of HIV progression and transmission. Anti-retroviral therapy (ART) has been reported to reduce HIV transmission by lowering VL. However, apart from this beneficial effect, increased levels of population mean set-point viral load (SPVL), an estimator for HIV virulence, have been observed in men who have sex with men (MSM) in the decade following the introduction of ART in The Netherlands. Several studies have been devoted to explain these counter-intuitive trends in SPVL. However, to our knowledge, none of these studies has investigated an explanation in which it arises as the result of a sexually transmitted infection (STI) co-factor in detail. In this study, we adapted an event-based, individual-based model to investigate how STI co-infection and sexual risk behaviour affect the evolution of HIV SPVL in MSM before and after the introduction of ART. The results suggest that sexual risk behaviour has an effect on SPVL and indicate that more data are needed to test the effect of STI co-factors on SPVL. Furthermore, the observed trends in SPVL cannot be explained by sexual risk behaviour and STI co-factors only. We recommend to develop mathematical models including also factors related to viral evolution as reported earlier in the literature. However, this requires more complex models, and the collection of more data for parameter estimation than what is currently available.