Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

Table 1

Cerebrospinal fluid concentration of some antiretrovirals as a percentage of plasma concentration and their CPE ranking.

Antiretroviral drug	Sample size	CSF concentration as a percentage of plasma concentration (%)		References	Revised CPE rank [22]
		Median (range)	Mean (SD)
Zidovudine	50	60 (4–262)		[133]	4
	18	2 (0–674)		[134]
	5		96 (8)	[135]
Abacavir	54	36		[136]	3
	3	35 (31–44)		[137]
Lamivudine	55	23 (0–490)		[134]	2
Stavudine	31	20 (0–20.4)		[134]	2
Didanosine	4		27 (14)	[135]	2
	5	Undetected		[134]
Tenofovir	38	5.7 (3–10)		[84]	1
Efavirenz	69	0.5 (0.26–0.76)		[138]	3
	11	Undetected		[134]
	26		0.71 (0.37) in 600 mg	[139]
	11	1.3 (0.8–1.6)		[140]
Nevirapine	16	63 (41–77)		[134]	4
Indinavir	19		1.7 (88.6)	[141]	3
	22	16 (0.4–228) or 6 using; AUC ratio		[142]
Lopinavir/r	26	0.23% (0.12–0.75)		[88]	3
	12		0.85 (0.47)	[143]
Nelfinavir	6	Not detected in CSF		[144]	1
	9	Not detected in CSF		[134]
Ritonavir	8	0.00 (0.00–52)		[134]	1
Darunavir/r	14		0.5	[145]	3
	14	0.9 (0.3–1.8)		[87]
Atazanavir	9	1.12 (0.5–13.9)		[146]	2
	8	1.4 (0.6–3.4)		[140]
	13		3	[145]
Raltegravir	41	17 (1.8–33.8)		[140]	3
	24	3 (1–61)		[147]
	35	20.6 (0.5–133)		[148]
Dolutegravir	12		0.546 (0.480)	[149]	N/A
Maraviroc	7	3.0 (1–10)		[150]	3
	12	2.2 (0.4–17)		[151]
	12		1.01 (0.29), 4.20 (1.22)	[143]

Subjects with multiple plasma and CSF samples, median (IQR), mean (coefficient of variation), geometric mean, % Maraviroc CSF/unbound plasma ratio, and N/A = not available. The ranks assigned to the antiretrovirals in Table 1 are based on revised ranking system proposed by Letendre et al. and not CSF/plasma ratio from the authors findings in the table. Higher CPE score means higher CNS penetration.