Comparison of ritonavir plus saquinavir- and nelfinavir plus saquinavir-containing regimens as salvage therapy in children with human immunodeficiency type 1 infection

Background. In this retrospective study we compared the antiretroviral effe ct of regimens consisting of simultaneous administration of two protease in hibitors (PI) with at least one nucleoside reverse transcriptase inhibitor an plasma viral load (VL) and CD4 cell count in HIV-infected children inten sively pretreated with nucleoside reverse transcriptase inhibitors and PIs. Methods, Eleven HIV-infected children were changed to antiretroviral combin ation regimens including two PIs and followed for a median time of 24 weeks . Group A comprised six patients who were given ritonavir + saquinavir (SQV ) and Group B consists of five patients who were changed to nelfinavir + SQ V. Patients were treated with these combinations with 2 PIs because of trea tment failure (increasing viral load) of prior PI therapy or clinical signs of disease progression, Outcome measures. Serial determinations of plasma viral load (Amplicor, Roche) and CD4 cells were performed every 4 to 8 week s, The detection limit of the Amplicor-reverse transcriptase-PCR assay was 50 copies/ml (1.7 log(10)). Results. In Group A the median VL reduction was 1.1 log(10) after 3 months and 1.4 log(10) after 6 months. In Group B median VL decreased 0.1 and 0.2 log(10) after 3 and 6 months. In both groups during the study period none o f the patients reached undetectable VL. The relative changes of CD4 cells a bove baseline in Group A showed a median increase of 7% after 3 months and 23% after 6 months. In Group B after 3 months CD4 cells did not increase, a nd after 6 months the median relative increase was only 7%. Both combinatio n therapies were well tolerated, not necessitating any drug interruption du ring study period. Conclusions. In children with intensive prior antiretroviral treatment, a s alvage therapy including two PIs demonstrated antiretroviral efficacy in so me patients. In this study the reduction of the VL as well as the increase of CD4 cells was more pronounced with ritonavir + SQV than with nelfinavir + SQV. With both combinations complete suppression of HIV replication was n ot achieved, Therefore the long term effect of these combinations may be li mited by the emergence of resistant HIV strains.