These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: A once-daily HAART regimen containing indinavir + ritonavir plus one or two nucleoside reverse transcriptase inhibitors (PIPO study).
    Author: Burger DM, Aarnoutse RE, Dieleman JP, Gyssens IC, Nouwen J, de Marie S, Koopmans PP, Stek M, van der Ende ME.
    Journal: Antivir Ther; 2003 Oct; 8(5):455-61. PubMed ID: 14640393.
    Abstract:
    INTRODUCTION: There is an increased interest in developing once-daily regimens for the treatment of HIV-infected patients. A Phase II study was conducted to investigate the pharmacokinetics, and short-term safety and efficacy of an indinavir/ritonavir combination as part of a once-daily regimen. METHODS: HIV-infected patients with either proven poor compliance to HAART regimens in the past or an anticipated poor compliance to such a regimen in the future were eligible for this study. They received a once-daily regimen consisting of indinavir 1200 mg, ritonavir 400 mg, and one or two nucleoside reverse transcriptase inhibitors (NRTIs), also administered once daily with food. A 24 h pharmacokinetic profile was constructed in a subset of patients. Short-term safety and efficacy were evaluated at 4, 12 and 24 weeks after initiation of treatment. RESULTS: A total of 64 patients were included in this study, of whom 27 (42.2%) were treatment-naive. The geometric mean (+95% CI) of indinavir AUC0-24h, Cmax and Cmin as determined in an unselected group of 16 patients were 84.9 (69.7-103.5) mg/l x h, 12.0 (10.2-14.1) mg/l and 0.15 (0.09-0.26) mg/l, respectively. A large interpatient variability was observed, with five out of the 16 subjects having a Cmin value below the minimum effective concentration of 0.10 mg/l. During the 24 weeks of follow-up nine patients (14.1%) discontinued study medication, two due to medication-related toxicity. Gastrointestinal adverse events were reported most frequently (50.0%), followed by skin effects (45.3%), joint pain (9.4%) and urological complaints (7.8%). No patient developed nephrolithiasis. The median (+interquartile range) serum creatinine level in the 64 patients increased slightly from 74 (63-88) micromol/l to 79 (66-92) micromol/l during the 24 weeks of follow-up. One new patient reached a grade 1 elevation in serum creatinine, which normalized during the follow-up; five other patients with elevated serum creatinine at baseline remained stable. During the 24 weeks of follow-up, the proportion of patients with a viral load <500 copies/ml increased from 35.1% at baseline to 71.4% (ITT NC=F analysis) or 83.3% (OT analysis), and from 0% at baseline to 76.2% (ITT NC=F analysis) or 100.0% (OT analysis) in treatment-experienced and -naive patients, respectively. This was accompanied by a mean increase in CD4 cell count of 52 and 220 cells/mm3 in these two sub-groups, respectively. CONCLUSION: The 24-week follow-up data of this study indicate favourable pharmacokinetics of an indinavir/ritonavir 1200/400 mg combination as part of a once-daily regimen consisting also of one or two NRTIs. Short-term safety and efficacy were also satisfactory. Long-term follow up is planned to evaluate the durability of these results.
    [Abstract] [Full Text] [Related] [New Search]