Predictive factors for response to a boosted dual HIV-protease inhibitor therapy with saquinavir and lopinavir in extensively pre-treated patients.

OBJECTIVE: To evaluate predictive factors for therapy outcome of a boosted double-protease inhibitor (PI) regimen in 58 extensively pre-treated patients with HIV.

METHODS: Patients received lopinavir/ritonavir 400/100 mg and saquinavir 1,000 mg twice daily without reverse transcriptase inhibitors (RTI). The primary outcome parameter was HIV RNA < 400 copies/ml at week 48, secondary parameters were HIV-1 RNA and CD4+ T-cell count changes from baseline to week 48. Pharmacokinetics, genotypic resistance and clinical and individual parameters were correlated with the clinical outcome in regression analyses. Covariates for the analyses were minimum plasma concentration (C(min)), maximum plasma concentration, area under the concentration versus time curve, half-life and clearance of lopinavir and saquinavir, the genotypic inhibitory quotients (GIQ) of archived (GI6(arch)) and baseline PI resistance mutations, previously taken antiretrovirals, archived and baseline viral resistance mutations, baseline HIV-1 RNA and CD4+ T-cell count.

RESULTS: The analyses detected correlations between the primary outcome parameter and several factors: baseline CD4+ T-cell count (P = 0.001); absence of mutations at V82T/A/F/I/S plus 154M/V/L (P = 0.002) or K20M/R (P = 0.010); and lopinavir C(min)GIQ(arch) (P = 0.046). This regression model had a predictability of 97.0% for response to therapy. Covariates for the decrease of HIV-1 RNA from baseline to week 48 were baseline HIV-1 RNA (P < 0.001), lopinavir C(min)GIQ(arch) (P = 0.013), presence/absence of mutations at V82T/A/F/I/S or 184A/V plus L10I/R/V/F, 154M/V/L or L63P (P = 0.018), and previously taken antiretrovirals (P = 0.034).

CONCLUSIONS: Baseline HIV-1 RNA < 5.0 log10 and CD4+ T-cell count > 200 cells/microl, lopinavir C(min)GIQ(arch) > 2,000 ng/ml and the absence of viral resistance mutations at V82T/A/F/I/S and 154M/V/L are highly predictive for therapeutic success of a regimen of saquinavir/lopinavir/ ritonavir without RTI in a heterogenic cohort of patients with an extensive pre-treatment history and highly variable pharmacokinetics.