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The Body Covers: The 12th Conference on Retroviruses and Opportunistic Infections

CNS Penetration of Antiretroviral Agents May Not Be Essential for Prevention of AIDS-Related Dementia

Coverage provided by Paul E. Sax, M.D.

February 25, 2005

The incidence of AIDS-related dementia has declined substantially since the introduction of potent antiretroviral therapy. One area of controversy, however, has been whether drugs used to treat HIV must penetrate into the central nervous system (CNS) for this beneficial effect to occur. This has always been a particular concern with drug classes that have relatively poor CNS penetration, such as the protease inhibitors (PIs).

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.

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