BACKGROUND In this retrospective study the effect of antiretroviral combination regimens including the non nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (EFV) on viral load (VL) and CD4-cell count in heavily pretreated HIV-infected children was investigated. METHODS The data of 15 children (< 16 years) were evaluated during a treatment period of at least 52 weeks. Patients received a median of 4 prior antiretroviral regimens and were changed to combinations with EFV because of renewed increasing VL. METHODS Viral load (Amplicor, detection limit 50 copies/ml) and CD4-cells were measured every 4-8 weeks. RESULTS The median reduction of the viral load for the total study population was 1.9 log10 (0.8 - 4.7), 2.3 log(10) (0.5 - 4.7) and 2.6 log(10) (0-4.7) after 12, 24 and 52 weeks, respectively. After 24 weeks 7/15 children and after 52 weeks 9/15 patients had reductions of the VL below the detection limit. The median increase of CD4-cells in the study population during the treatment period were 104 cells/microl (189-969), 220 cells/microl (170-831) and 321 cells/ml (162-574) after 12, 24 and 52 weeks, respectively. CONCLUSIONS In children with intensive prior antiretroviral therapy and multiple therapeutic failures with PI-containing regimens, combination therapy including EFV resulted in an excellent antiretroviral efficacy. After 52 weeks 9/15 patients had persistent reductions of the VL below 50 copies/ml, although none of these children reached this level of viral suppression during their multiple prior protease inhibitor-containing regimens.