The primary objective of this retrospective study was to determine how many patients in routine practice who were treated with combination antiretroviral treatment reached HIV-1 RNA levels below 50-400 copies/ml in cerebrospinal fluid (CSF). Seventy-four antiretroviral-naive HIV-1-infected patients from five different centres in Germany, Italy, Sweden and the USA were included. Thirty-nine percent of the patients had a HIV-1-associated neurological disease and 53% of the patients had AIDS. HIV-1 RNA in CSF and plasma were quantified before and after approximately 3 months of treatment. At baseline, the median value of HIV-1 RNA in CSF was 4.12 log copies/ml (interquartile range (IQR): 3.28-4.85) and it decreased to < 1.70 log copies/ml (IQR: < 1.70-2.48; P < 0.001) after in median 3 months of treatment. Seventy-six percent of the patients had HIV-1 RNA levels below the limits of detection in CSF at follow-up, and 85% reached below 400 copies/ml. In plasma, 45% of the patients had levels of HIV-1 RNA below the limits of detection at follow-up and 80% reached below 400 copies/ml. The group of patients with a neurological disease had a significantly higher CSF viral load both at baseline and at follow-up compared with the neurologically asymptomatic patients. We conclude that the central nervous system (CNS) is usually not a 'sanctuary site', difficult to reach with combination antiretroviral treatment.