Kaletra monotherapy can reduce levels of HIV in the brain

For the first time a single anti-HIV medication, ritonavir-boosted lopinavir (Kaletra), has been shown to bring down levels of HIV in the cerebrospinal fluid. The authors of the report, published in the online edition of Clinical Infectious Diseases, assert that the medication may be of particular help to patients with HIV-associated neurologic disorders.

Opinions on the best way to fight AIDS-related brain infections are mixed. Some studies suggest that increasing the CD4 cell count is the best protection while others highlight the value of anti-HIV drugs that can penetrate into the cerebrospinal fluid (CSF) of the central nervous system (CNS) and suppress viral replication there. Supporting the latter, a report from the recent European AIDS Conference noted that while survival from AIDS-related neurologic conditions has generally improved since the advent of highly active antiretroviral therapy, the best survival has been seen among patients who received drugs that enter the CSF.

Studies into the ability of a single antiretroviral to suppress HIV in CSF are difficult because anti-HIV drugs must usually be given in combination to be effective. However, Kaletra provides an exception: its pharmacokinetics, potency and high barrier to genetic mutation allow for monotherapy; this strategy is currently being tested in several clinical trials.

Taking advantage of these characteristics, Scott Letendre and colleagues from the University of California, San Diego and from Abbott Laboratories tested the ability of Kaletra to suppress HIV replication in the CSF. In the study, participants received Kaletra monotherapy for three weeks. Then, a full antiretroviral regimen was added, and participants were followed up at weeks 12 and 24. Blood and CSF samples taken at these three time points were assayed for viral load.

Of the 15 participants enrolled, eight completed the study. Investigators withdrew two participants after three weeks: one due to increased liver enzyme levels and the other due to virologic failure.

At study start, participants were treatment naïve with median baseline CD4 cell count of 207 cells/mm³ and median viral load of 4,900 copies/ml in CSF and 145,000 copies/ml in plasma. Ten participants had AIDS. Median age of the group was 38 years and 87% of the group was male.

Three weeks of Kaletra monotherapy decreased viral load in both CSF and plasma. The median decrease in CSF viral load was -1.42 log₁₀ copies/ml, while the median decrease in plasma was -1.8 log₁₀ copies/ml. Two subjects had an undetectable (

Participants then received combination therapy. At week 24, nine patients remained. Of those, eight had undetectable viral load in both CSF and plasma samples.

HIV present in the CSF can come from two sources: virus that replicates in cells of the plasma and migrates into the CSF, or virus that replicates in the CNS. Using differences in the rate of decline in viral load between plasma and CSF, the researchers concluded that Kaletra was suppressing viral replication in the CNS in five patients.

HIV replication in the CNS is associated with advanced disease, which the researchers proposed would manifest as lower baseline CD4 cell counts. The five participants with signs of CNS viral replication tended towards having lower baseline CD4 cell counts than participants who did not show signs of CNS viral replication, though the difference was not statistically significant (p = .068).

The researchers also noted that five participants started the study with signs of impaired global cognitive performance. Of the three who completed the study, all showed improvements in function to within the normal range.

While acknowledging the limitations of the study, including its open-label design and small size, the researchers highlight that it is the first to show that one anti-HIV medication alone can reduce viral load in CSF. They also state that Kaletra appears to reduce HIV replication in the central nervous system.