February 25, 2005
This study, presented here by G. van den Brande from the University of California-San Diego and colleagues, sought to establish whether lopinavir/ritonavir (LPV/r, Kaletra) -- a PI that is highly protein bound -- can lower CNS viral load levels in patients even when used as a single agent as part of initial therapy.
Thirteen participants enrolled in the study and began taking lopinavir/ritonavir alone for 3 weeks. Cerebrospinal fluid (CSF) sampling was done at baseline and at 3 weeks in 10 subjects.
At the start of the study, the HIV-RNA level in the plasma was 5.20 log, and in CSF 3.63 log -- a commonly observed 1 to 2 log difference between plasma and CSF. In paired plasma and CSF samples, lopinavir/ritonavir monotherapy was effective in lowering HIV-RNA levels in both compartments, with reductions of 1.7 log and 1.4 log, respectively. Interestingly, patients with more advanced HIV disease (based on higher viral loads and lower CD4+ cell counts) experienced a more rapid decline in CSF HIV RNA.
This small study has important implications for the ongoing development of lopinavir/ritonavir and other boosted PIs as single-agent therapies, either as initial treatment or as maintenance therapy. The data suggest that CNS penetration of antiretroviral agents may not be essential in the prevention of AIDS-related dementia and other neurologic complications of HIV. In addition, the data provide pathophysiologic support for the dramatic decline in AIDS dementia in the current treatment era, a reduction that has occurred with all therapies regardless of their CNS penetration.