PURPOSE: To study the relationship between drug use and adherence to highly active antiretroviral therapy (HAART) among HIV-positive people, with two alternative measures of drug use: a set of drug uses considered independent and patterns capturing combinations of drug uses. METHODS: A cross-sectional survey conducted among a nationally representative sample of 4963 HIV-positive people randomly recruited in 102 French hospital departments delivering HIV care. The researchers modelled non-adherence to HAART with a set of binary indicators of drug use (model I) or comprehensive patterns obtained with a cluster analysis (model II). RESULTS: In model 1, heroin use, injection drug use, and cocaine/amphetamine/ecstasy use were not significant predictors of poor adherence in contrast with nicotine dependence, cannabis use, and amyl nitrate use. In model II, non-adherence to HAART was more prevalent among profiles characterised by alcohol abuse and multiple addictions, including nicotine dependence and use of various illicit drugs. CONCLUSIONS: Nicotine dependence, cannabis use, and amyl nitrate use are associated with non-adherence only if they are embedded in drug use patterns characterised by alcohol abuse or heroin use. The results also illustrate the interest in investigating the effects of drug use patterns on behavioural outcomes, rather than measuring independent effects of various drug use indicators that are highly correlated.