In:
Antiviral Therapy, SAGE Publications, Vol. 12, No. 8 ( 2007-11), p. 1237-1246
Abstract:
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 (GIQ 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 I54M/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 I84A/V plus L10I/R/V/F, I54M/V/L or L63P ( P=0.018), and previously taken antiretrovirals ( P=0.034). Conclusions Baseline HIV-1 RNA 〈 5.0 log 10 and CD4 + T-cell count 〉 200 cells/μl, lopinavir C min GIQ arch 〉 2,000 ng/ml and the absence of viral resistance mutations at V82T/A/F/I/S and I54M/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.
Type of Medium:
Online Resource
ISSN:
1359-6535
,
2040-2058
DOI:
10.1177/135965350701200803
Language:
English
Publisher:
SAGE Publications
Publication Date:
2007
detail.hit.zdb_id:
2118396-X
SSG:
15,3
