Haas D, Clough L, Johnson B, Bermingham K, McKinsey J, Donlon R, Spearman P, Wilkinson G, Harris V, Shoup R, Farnsworth A, Lillibridge J; Conference on Retroviruses and Opportunistic Infections.
7th Conf Retrovir Oppor Infect Jan 30 Feb 2 2000 Conf Retrovir Oppor Infect 7th 2000 San Franc Calif. 2000 Jan 30-Feb 2; 7: 135 (abstract no. 313).
Vanderbilt Univ., Nashville, TN.
Objectives: NFV has been reported to be undetectable in CSF by HPLC analysis. The present study utilized a more sensitive LC/MS assay to quantify NFV and M8 in CSF, and ultra-intensive CSF sampling to characterize the CSF virologic response during the first week of therapy. Methods: Four asymptomatic, treatment naive adults initiated NFV (750mg q8h), d4T, and 3TC. CSF was collected continuously during 48-hr intervals by lumbar catheter at baseline and again beginning on treatment day 4. Plasma was sampled serially. NFV and M8 were quantified in CSF by LC-MS, and in plasma by HPLC. Results: NFV and M8 were present in CSF throughout the dosing interval in every patient; however, loss of NFV and M8 on CSF sampling catheters prevented precise quantification. Two subjects later underwent single lumbar punctures, at which time total CSF drug levels (NFV + M8) were 9.4 nM and 11.8 nM. CSF HIV-1 RNA change from baseline to treatment Day 4 ranged from -0.38 to -1.18 log10 copies/mL. HIV-1 RNA decline in CSF correlated with plasma M8 peak level (r=0.987, P=0.013) and AUC0-8hr (r=0.985, P=0.015). HIV-1 RNA decline in plasma did not correlate with CSF response. Conclusions: The correlation between plasma M8 pharmacokinetic parameters and CSF virologic response suggests that NFV may play a greater role in controlling HIV-1 replication in the CNS than previously appreciated. Both NFV and its active metabolite are present in CSF throughout the dosing interval.
Publication Types:
Keywords:
- Adult
- Chromatography, High Pressure Liquid
- HIV-1
- Humans
- Lamivudine
- Nelfinavir
- Stavudine
Other ID:
UI: 102243191
From Meeting Abstracts