Cerebrospinal fluid HIV-1 RNA during treatment with ritonavir/saquinavir or ritonavir/saquinavir/stavudine

Objective: To assess the HIV-1-RNA response and drug concentrations in cere brospinal fluid (CSF) and serum during treatment with saquinavir (SQV)/rito navir (RTV) or SQV/RTV plus stavudine (d4T) in HIV-1-infected patients. Design: A multicentre, open-label, randomized controlled trial. Methods: A total of 208 protease inhibitor (PI) and d4T-naive, HIV-1-infect ed patients were treated with RTV 400 mg twice daily and SQV 400 mg twice d aily with or without d4T 40 mg twice daily. Intensification with reverse tr anscriptase inhibitors was allowed if serum HIV RNA remained above 400 copi es/ml after 12 weeks. In 27 volunteers, CSF and serum HIV RNA were measured at baseline, weeks 12 and 48, using the Roche Amplicor and the ultrasensit ive assay. In 22 patients, serum and CSF drug concentrations were determine d at week 12. Results: The median baseline serum and CSF HIV-RNA concentrations were 4.81 and 3.21 log(10) copies/ml, respectively. A difference in the proportion o f patients with a CSF: HIV-RNA level below the limit of quantification (< L LQ) after 12 weeks was found: four out of 14 (RTV/SQV) versus 12 out of 13 (RTV/SQV/d4T) (P = 0.001). The same results were found using the ultrasensi tive assay. Patients with a baseline HIV-RNA level < LLQ in CSF remained < LLQ, regardless of the treatment regimen. Treatment with RTV/SQV alone was the only independent predictor of a CSF HTV-RNA level > LLQ at week 12 in l ogistic regression analysis (P = 0.005). CSF RTV and SQV concentrations wer e < LLQ in most patients. Conclusion: RTV/SQV alone cannot suppress detectable CSF HIV-1-RNA levels t o < LLQ after 12 weeks of treatment in the majority of patients. CSF drug c oncentrations of RN and SQV < LLQ may explain the suboptimal antiretroviral effect in the CSF. (C) 2000 Lippincott Williams & Wilkins.