CNS penetration of ARV drugs is associated with lower CSF viral load

Simon Collins, HIV i-Base

Letendre and colleagues from San Diego reported results from the Chapter Study, which assigned individual ARVs a CNS penetration index of 0 (low), 0.5 (intermediate) or 1 (high), based on published data and chemical properties (see Table 1).

They measured plasma and CSF viral load in 374 HIV-positive patients taking at least one ARV who were prospectively enrolled for the study.

Results from the study showed that higher penetration scores correlated with lower CSF viral load, which remained significant in a multivariate modal that adjusted for number of ARVs used for each patient, and plasma viral load (model r2 = 0.34, p <0.0001). In contrast, penetration scores did not correlate with plasma viral load (p = 0.26).

The study concluded that better penetration of ART across the blood-CSF barrier led to better control of HIV replication in CSF and that as inhibition of HIV replication in the CNS is important in treating patients who have HIV-associated neurocognitive disorders, they may benefit from CNS-targeted ART therapy.

Table 1: Assigned CSF penetration based on published data and chemical properties

Increasing CNS penetration
0 0.5 1.0
NRTI TDF, ddI 3TC, FTC, d4T AZT, abacavir
NNRTI efavirenz nevirapine, delavirdine
PI nelfinavir, ritonavir amprenavir/fosamprenavir amprenavir/r, fosamprenavir/r
saquinavir, saquinavir/r indinavir indinavir/r, lopinavir/r
tipranavir/r atazanavir atazanavir/r


CSF penetration is generally more important to consider for patients with neurologic symptoms. The table on CSF penetration from one of the expert groups in this field is useful.


Letendre S, Capparelli E, Simpson D et al. Better antiretroviral penetration into the central nervous system is associated with lower CSF viral load. 13th Conference on Retroviruses and Opportunistic Infections, 5-8 February 2006, Denver, Colorado. Abstract 74.

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