1. Home>
2. Specialties>
3. HIV/AIDS Clinical Care>
4. Summary and Comment

Enhancing Antiretroviral Activity in the Brain

Receiving a combination of drugs that have strong penetration into the CNS reduces the likelihood of having detectable virus in the CSF.

Even in this era of effective HIV treatment, the central nervous system (CNS) remains an ominous black box. Some data suggest that rates of HIV-associated neurologic disease are as high as ever, but clinicians seldom consider drug penetration into the CNS when devising treatment regimens. Should they?

As a first step to answering this question, investigators from a nationwide research consortium sought to determine whether drug penetration into the CNS correlated with detectable virus in cerebrospinal fluid (CSF). Of 467 patients on ART between 2003 and 2006, 29% were receiving PI-based regimens, 37% were receiving NNRTI-based regimens, and the rest were receiving 3-drug or 2-drug NRTI combinations, for a total of 166 different drug combinations. For each combination, the researchers devised a "CNS penetration–effectiveness (CPE)" rank by using published data to estimate the CSF penetration of each individual drug as high (1 point), medium (0.5 points), or low (0 points) and then summing the results.

Forty-three percent of patients had detectable serum viral loads, but only 17% had detectable HIV RNA in CSF. A low CPE rank proved to be a risk factor for detectable CSF viral load, independent of plasma viral load, adherence, CD4-cell count, total number of drugs in the regimen, type of regimen, and duration of treatment.

Comment: These data make physiologic sense; the next question is whether drugs with high CSF penetration treat HIV-associated neurologic syndromes more effectively than others. That assumption also makes sense, and clinicians may wish to act on it, but unfortunately, much of the data behind the index used here comes from pharmacokinetic or nonclinical chemical studies and may be difficult to obtain and interpret. These authors would have done clinicians a service by supplying some examples of regimens with unusually high CPE ranks; unfortunately, they elected not to do so.

— Abigail Zuger, MD

Published in Journal Watch HIV/AIDS Clinical Care June 2, 2008

Citation(s):

Letendre S et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008 Jan; 65:65.

• Original article (Subscription may be required)
• Medline abstract (Free)