BACKGROUND The clinical data of plasma NVP level, safety and efficacy of antiretroviral therapy (ART) for the concurrent use of nevirapine (NVP)-based ART and fluconazole (FLU) is scanty. METHODS A retrospective study was conducted in patients who were initiated NVP-based ART between October 2004 and November 2005. The objectives were to compare NVP levels, adverse events, and 36-week efficacy of NVP-based ART between patients who did not receive FLU (group A) and those who received FLU 200 mg/day or 400 mg/day (group B). RESULTS There were 122 patients with mean +/- SD age of 36 +/- 9 years; 81 in group A and 41 in group B. Median (IQR) baseline CD4 cell count was 29 (8-79) cell/mm3 in group A and 19 (8-33) cell/mm3 in group B (P = 0.102). Baseline characteristics between the two groups were similar. Mean +/- SD NVP levels were 6.5 +/- 3.0 mg/L in group A and 11.4 +/- 6.1 mg/L in group B(P < 0.001). One (2.4%) patient in group B developed clinical hepatitis (P = 0.336). Six (7.4%) patients in group A developed NVP-related skin rashes (P = 0.096). There were no differences in term of 36-week antiviral efficacy between the two groups (P > 0.05). CONCLUSIONS Co-administration of NVP and daily dosage of FLU (200 mg/day and 400 mg/day) results in markedly increased trough plasma NVP level when compared to the administration of NVP alone. The concurrent use of NVP and FLU in very advanced HIV-infected patients is well-tolerated. The immunological and virological responses are favorable.