title: High-dose saquinavir plus ritonavir: long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response.
abstract: The year-long antiviral efficacy of a high-dose salvage regimen consisting of saquinavir (800 mg twice daily) plus ritonavir (400 mg twice daily) was evaluated in 58 HIV-positive patients who had seen no improvement under first-line protease inhibitor-containing regimens, nor in baseline predictors of virologic response. The efficacy of therapy was determined by CD4+/CD8+ and HIV-1 RNA values. The primary endpoint of our study was the percentage of patients with HIV-1 RNA levels <200 copies/ml (virologic success) at 6 and 12 months of of follow-up. Secondary endpoints were log10 reduction in HIV-1 RNA levels and CD4+ increases through follow-up. Surrogate markers related with a lower HIV-1 RNA area under the curve were identified at baseline. Kaplan-Meier analysis and Cox proportional hazards models were applied to identify baseline predictors of achieving viral suppression at <200 copies/ml. All analyses were intention to treat-last observation carried forward. Patients achieved a median HIV-1 RNA level reduction of >0.5 log through 1 year (-0.59 log10 at 12 months), as well as CD4+ counts increased significantly (89 cells/mm3 at 12 months). Overall, 53% of patients were likely to achieve HIV-1 RNA levels <200 copies/ml at 6 months. Seventy-six percent of patients who started therapy at HIV-1 RNA levels <5000 copies/ml but only 42% with baseline viral load of 5000 to 30,000 copies/ml and 18.7% with baseline viral load >30,000 copies/ml were likely to achieve viral suppression at 6 months (p < .001, log-rank test). Patients with baseline HIV-1 RNA levels between 5000 and 30,000 copies/ml (relative hazard [RH], 0.39; 95% confidence interval [CI], 0.01 to 0.98; p = .0396) and patients with baseline HIV-1 RNA levels >30,000 copies/ml (RH, 0.20; 95% CI, 0.07-0.61; p = .0040) were less likely to reach undetectable HIV-1 RNA levels than those with baseline HIV-1 RNA levels <5000 copies/ml. Salvage highly active antiretroviral therapy (HAART) strategies including saquinavir (SQV) at high doses plus ritonavir (RTV) exert a significant long-term efficacy in more than half of PI-experienced patients without significant additional toxicity. This therapeutic efficacy is strongly implemented by a switch at the lower HIV-1 RNA levels.
authors.affiliation: Retrovirology Laboratory Institut de Recerca de la SIDA-Caixa, Hospital Universitari Germans Trias i Pujol, Badalona, Catalonia, Spain. univih@ns.hugtip.scs.es
authors.forename: R
authors.initials: R
authors.lastname: Paredes
authors.forename: T
authors.initials: T
authors.lastname: Puig
authors.forename: A
authors.initials: A
authors.lastname: Arnó
authors.forename: E
authors.initials: E
authors.lastname: Negredo
authors.forename: M
authors.initials: M
authors.lastname: Balagué
authors.forename: A
authors.initials: A
authors.lastname: Bonjoch
authors.forename: A
authors.initials: A
authors.lastname: Jou
authors.forename: A
authors.initials: A
authors.lastname: Tuldrà
authors.forename: C
authors.initials: C
authors.lastname: Tural
authors.forename: G
authors.initials: G
authors.lastname: Sirera
authors.forename: A
authors.initials: A
authors.lastname: Veny
authors.forename: J
authors.initials: J
authors.lastname: Romeu
authors.forename: L
authors.initials: L
authors.lastname: Ruiz
authors.forename: B
authors.initials: B
authors.lastname: Clotet
mesh_terms: D000328:Adult; D004334:Drug Administration Schedule; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D019370:Observation; D012189:Retrospective Studies; D012307:Risk Factors; D019438:Ritonavir / Q000008:administration & dosage / Q000627:therapeutic use*; D016879:Salvage Therapy; D019258:Saquinavir / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors; D019258:Saquinavir; D019438:Ritonavir