OBJECTIVES: To analyse the association between the presence of resistance mutations and treatment outcomes. The impact of HIV-1 drug resistance mutations in African adults on HAART has so far never been reported. METHODS: In 2004 in Abidjan, C?d'Ivoire, 106 adults on HAART had plasma viral load measurements. Patients with detectable viral loads had resistance genotypic tests. Patients were followed until 2006. Main outcomes were serious morbidity and immunological failure (CD4 cell count < 200 cells/microl). RESULTS: At study entry, the median previous time on HAART was 37 months and the median CD4 cell count was 266 cells/microl; 58% of patients had undetectable viral loads, 20% had detectable viral loads with no major resistance mutations, and 22% had detectable viral loads with one or more major mutations. The median change in CD4 cell count between study entry and study termination was +129 cells/microl in patients with undetectable viral loads, +51 cells/microl in those with detectable viral loads with no mutations and +3 cells/microl in those with detectable viral loads with resistance mutations. Compared with patients with undetectable viral loads, those with detectable viral loads with resistance mutations had adjusted hazard ratios of immunological failure of 4.32 (95%CI 1.38-13.57, P = 0.01). One patient died. The 18-month probability of remaining free of morbidity was 0.79 in patients with undetectable viral loads and 0.69 in those with resistance mutations (P = 0.19). CONCLUSION: In this setting with restricted access to second-line HAART, patients with major resistance mutations had higher rates of immunological failure, but most maintained stable CD4 cell counts and stayed alive for at least 20 months.