UNIGE document Scientific Article
previous document  unige:7419  next document
add to browser collection
Title

Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study

Authors
Lorenzi, P.
Abderrakim, K.
von Overbeck, J.
Leduc, D.
show hidden authors show all authors [1 - 9]
Published in AIDS. 1997, vol. 11, no. 12, p. F95-99
Abstract OBJECTIVE: To assess the safety, efficacy and plasma drug levels of the combination of ritonavir plus saquinavir for the treatment of advanced HIV infection. DESIGN: Multicentre pilot study. PATIENTS: Eighteen protease inhibitor-naive patients, with intolerance or contraindication to reverse transcriptase inhibitors, a median CD4 cell count of 12 x 10(6)/l (range, 1-50 x 10(6)/l), and a median HIV viraemia of 5.25 log10 copies/ml (range, 4.00-6.13 log10 copies/ml). METHODS: Patients received 600 mg twice daily of both ritonavir and saquinavir. Viraemia was measured at baseline and at weeks 5, 9 and 13. Response was defined as a drop of viraemia of more than 1 log10 at week 5. Plasma drug levels were determined after at least 3 weeks of combined treatment: samples were collected before and 1, 2, and 4 h after the morning ingestion of both drugs. The protease gene was sequenced at baseline and under treatment. RESULTS: Among the 16 patients evaluable at week 5, 11 were responders, and among these patients, six remained responders at week 13 (two with undetectable viraemia). Study discontinuations were due to side-effects (n = 4), patient choice (n = 3), protocol violation (n = 1) and death (n = 1). Responders had higher drug levels than non-responders (P < 0.01 for saquinavir, P = 0.04 for ritonavir). In two non-responders, development of multiple new mutations at positions 10, 20, 48, 82, 84 and 90 was observed after 5-13 weeks. CONCLUSION: The response to ritonavir plus saquinavir in advanced HIV infection is unpredictable. A minority of patients respond with disappearance of HIV viraemia. In other patients, rapid cumulative emergence of protease mutations conferring resistance to treatment cannot always be prevented by good compliance and relatively high plasma drug levels.
Keywords Acquired Immunodeficiency Syndrome/blood/ drug therapyAnti-HIV Agents/adverse effects/pharmacokinetics/ therapeutic useCD4 Lymphocyte CountCD4-CD8 RatioCohort StudiesDrug Resistance, MicrobialDrug Therapy, CombinationFemaleHIV Protease/ geneticsHIV Protease Inhibitors/adverse effects/pharmacokinetics/ therapeutic useHumansMaleMutationPilot ProjectsRitonavir/adverse effects/pharmacokinetics/ therapeutic useSaquinavir/adverse effects/pharmacokinetics/ therapeutic useViremia/drug therapy
Identifiers
PMID: 9342060
Full text
Structures
Citation
(ISO format)
LORENZI, P. et al. Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir. Swiss HIV Cohort Study. In: AIDS, 1997, vol. 11, n° 12, p. F95-99. https://archive-ouverte.unige.ch/unige:7419

187 hits

2 downloads

Update

Deposited on : 2010-06-21

Export document
Format :
Citation style :