7th Conference - Abstract 309

Drug Levels and HIV-1 RNA in Serum and CSF during Treatment with a Five-Drug Regimen: AZT, 3TC, Abacavir, Nevirapine (NVP), and Indinavir (IDV)

J. PRINS¹*, R. VAN PRAAG¹, S. JURRIAANS¹, G. WEVERLING¹, P. PORTEGIES¹, J. P. SOMMADOSSI³, Z. ZHOU³, R. HOETELMANS², and J. LANGE¹. ¹Univ. of Amsterdam, and ²Slotervaart Hosp., Amsterdam, the Netherlands; and ³Univ. of Alabama, Birmingham

Background Antiretroviral drugs differ in their ability to enter the CSF, and CSF HIV-1 RNA levels during antiretroviral therapy may not necessarily reflect plasma HIV-1 RNA. We obtained drug levels and virological responses in plasma and CSF during treatment with a five-drug regimen, which has been shown to result in a more rapid decline of plasma HIV-1 RNA than a conventional three drug regimen.
Study design 15 patients were treated with AZT (2x300mg), 3TC (2x150mg), abacavir (2x300mg), nevirapine (2x200mg or lx400mg) and indinavir (3 x1000mg); in 7 pts IDV was changed in the combination IDV (2x800mg) + ritonavir (2x100mg) after 8 weeks. A serum pharmacokinetic profile was obtained and a CSF sample was collected 1 h after taking the drugs) at weeks 0 and 8.

* ng/ml, mean; ‡ mean; † difference between week 0 and week 8: p < .05
Median (range) baseline plasma VL was 4.9 (4.1–5.9) log copies/ml, at 8 weeks 2.0 (<0.7–3.8) log and at 48 weeks <0.7 (<0.7–2.0) log. Median (range) baseline CSF VL was 3.6 (2.5–5.7) log copies/ml, at 8 weeks <1.6 (<1.6–3.0) log and at week 48 <1.6 (<1.6–2.0) log.
Conclusions: Concentrations of AZT, 3TC, abacavir. and especially IDV in CSF were low. CSF levels of 3TC and IDV increased significantly during the first weeks of therapy. Despite the low drug levels, the virological response in CSF was good.

Key Words: abacavir, CSF, pharmacokinetics