High-dose saquinavir plus ritonavir: Long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response

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 fir st-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 percent age of patients with HIV-1 RNA levels <200 copies/ml (virologic success) at 6 and 12 months of of follow-up. Secondary endpoints were log(10) reductio n in HIV-1 RNA levels and CD4(+) increases through follow-up. Surrogate mar kers related with a lower HIV-1 RNA area under the curve were identified at baseline. Kaplan-Meier analysis and Cox proportional hazards models were a pplied to identify baseline predictors of achieving viral suppression at <2 00 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 log,, at 12 months), as well as CD4(+) counts increas ed significantly (89 cells/mm(3) at 12 months). Overall, 53% of patients we re likely to achieve HIV-1 RNA levels <200 copies/ml at 6 months. Seventy-s ix percent of patients who started therapy at HIV-1 RNA levels <5000 copies /ml but only 42% with baseline viral load of 5000 to 30000 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 wi th 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 t hose with baseline HIV-1 RNA levels <5000 copies/ml. Salvage highly active antiretroviral therapy (HAART) strategies including saquinavir (SQV) at hig h doses plus ritonavir (RTV) exert a significant long-term efficacy in more than half of PI-experienced patients without significant additional toxici ty. This therapeutic efficacy is strongly implemented by a switch at the lo wer HIV-1 RNA levels.