Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance
| Autor: | Marta Boffito, Diego Miralles, Alan Winston, Graeme Moyle, Anton Pozniak, Akil Jackson, Carl Fletcher, Brian Gazzard, Mark T. Nelson, Richard M. W. Hoetelmans, Izabela Tolowinska |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Enfuvirtide Immunology Etravirine HIV Infections Pharmacology Drug Resistance Viral Nitriles medicine Immunology and Allergy Humans Protease inhibitor (pharmacology) Darunavir Sulfonamides Ritonavir Reverse-transcriptase inhibitor business.industry HIV Protease Inhibitors Middle Aged Viral Load CD4 Lymphocyte Count Pyridazines Infectious Diseases Pyrimidines Anti-Retroviral Agents Area Under Curve HIV-1 RNA Viral Female business Viral load HIV drug resistance medicine.drug |
| Zdroj: | AIDS (London, England). 21(11) |
| ISSN: | 0269-9370 |
| Popis: | Cumulative antiretroviral exposure can result in multiclass HIV drug resistance. Experimental antiretroviral agents offer limited therapeutic benefit as resistance quickly develops after their introduction as a sole new agent.To assess the pharmacokinetic profile, safety and virological response of two novel investigational antiretroviral agents when used in combination in HIV-1-infected subjects with multidrug-resistant virus.HIV-1-infected subjects, with current virological failure on a stable antiretroviral regimen with no viable treatment options were assigned to a regimen comprising two new investigational agents, etravirine, a novel nonnucleoside reverse transcriptase inhibitor, and darunavir, a novel protease inhibitor, plus nucleoside reverse transcriptase inhibitors (and enfuvirtide in selected patients) for 24 weeks. Virological, immunological and safety parameters were collected. Detailed pharmacokinetic assessments of darunavir and etravirine were determined on days 7 and 28.Follow up of 24 weeks was achieved by 10/12 patients. Median reduction in HIV RNA was 2.7 log10 copies/ml (range, 2.3-3.9) and increase in CD4 lymphocytes was 113 cells/microl (range, 41-268). HIV RNA was40 copies/ml in nine. No serious adverse events were recorded. Plasma exposure to darunavir was similar to historic control data and exposure to etravirine similar to historic data when etravirine was administered with a boosted protease inhibitor.This first study to assess the use of etravirine and darunavir in HIV-1-infected subjects with no treatment options showed highly effective virological and immunological responses over 24 weeks of therapy with no new safety concerns or unexpected pharmacokinetic interactions. |
| Databáze: | OpenAIRE |
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