Browsing by Author "Lundgren, Jens D"

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    Continued indinavir versus switching to indinavir/ritonavir in HIV-infected patients with suppressed viral load
    (2003-04-11) Arnaiz, Juan A; Mallolas, Josep; Podzamczer, Daniel; Gerstoft, Jan; Lundgren, Jens D; Cahn, Pedro; Fätkenheuer, Gerd; D'Arminio-Monforte, Antonella; Casiró, Arnaldo; Reiss, Peter; Burger, David M; Stek, Michael; Gatell, Jose
    Objective: To compare continued indinavir (IDV) 8-hourly (q8h) with switching to indinavir/ritonavir (IDV/RTV) 12-hourly (q12h) in HIV-positive patients having suppressed viral load with IDV q8h plus two nucleoside reverse transcriptase inhibitors (NRTI). Design: Multicentre, international, randomized, open-label study enrolling HIV-1 infected patients on IDV 800 mg q8h plus two NRTI with CD4 cell counts > or = 100 x 106/l and plasma HIV RNA < 500 copies/ml for > or = 3 months. Methods: Patients were randomized to continue on the same regimen or to switch to IDV plus liquid RTV (IDV/RTV 800 mg/100 mg q12h). Primary endpoint was the proportion of patients remaining < 500 copies/ml at 48 weeks. Results: A total of 323 patients (IDV/RTV, 162; IDV, 161) were evaluable. At 48 weeks, the proportions of patients with plasma HIV RNA < 500 copies/ml were 93%, 88% and 58% in the IDV/RTV arm versus 92% (P = 1), 86% (P = 0.87) and 74% (P = 0.003) in the IDV arm using on-treatment (OT) and intent-to-treat (ITT) [switches included (ITT, S = I) and switches = failure (ITT, S = F)] analyses respectively. Mean increase in CD4 cell count was 88 x 106/cells/l (IDV/RTV arm) and 60 x 106 cells/l (IDV arm) (P = 0.08). More patients discontinued study medication due to adverse events in the IDV/RTV arm than in the IDV arm (P < 0.001). Conclusions: Equivalence of continuing IDV q8h versus switching to IDV/RTV (liquid) q12h in suppressed stable patients was demonstrated by OT and ITT S = I analyses. However, the IDV q8h arm performed better when discontinuations were classified as failures. IDV/RTV q12h can be convenient and equally effective for patients able to tolerate it
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    Pharmacokinetics of Two Randomized Trials Evaluating the Safety and Efficacy of Indinavir, Saquinavir and Lopinavir in Combination with Low-Dose Ritonavir: The MaxCmin1 and 2 Trials
    (2007-08-10) Justesen, Ulrik S; Fox, Zoe; Pedersen, Court; Cahn, Pedro; Gerstoft, Jan; Clumeck, Nathan; Losso, Marcello; Peters, Barry; Obel, Niels; Castagna, Antonella; Dragsted, Ulrik B; Lundgren, Jens D; n behalf of the MaxCmin1 and 2 trial groups
    Abstract: Our objective was to identify possible differences in protease inhibitor plasma concentrations between and within three protease inhibitor regimens (indinavir, saquinavir and lopinavir all in combination with low-dose ritonavir) and to relate these differences to safety and efficacy. Data originated from pre-defined pharmacokinetic substudies within two randomized 48-week trials evaluating the safety and efficacy of three protease inhibitor regimens. At weeks 4 and 48, plasma was collected and minimum drug plasma concentrations, Cmin, were obtained. Out of 656 randomized patients, 283 patients had available Cmin at week 4. Indinavir, saquinavir and lopinavir Cmin were high when combined with low-dose ritonavir. No significant difference in the proportion of patients experiencing treatment failure could be found according to the Cmin within any treatment arm. A saquinavir Cmin > 2000 ng/ml was associated with an increased risk of gastrointestinal grade 3 or 4 adverse events and higher total cholesterol. Overall, there were no changes in Cmin from week 4 to week 48 in patients who remained on therapy. No association between treatment failure and the Cmin could be demonstrated. Associations between high Cmin and toxicity were identified in the saquinavir arm; therefore, dose reductions may be appropriate in certain patients with Cmin several times above the minimum effective concentration.