Combination Therapy with Amprenavir, Abacavir, and Efavirenz in Human Immunodeficiency Virus (HIV)-Infected Patients Failing a Protease-Inhibitor Regimen: Pharmacokinetic Drug Interactions and Antiviral Activity

• Published in: Clinical infectious diseases 2000-02, Vol.30 (2), p.313-318
• Main Authors: Falloon, Judith, Piscitelli, Stephen, Vogel, Susan, Sadler, Brian, Mitsuya, Hiroaki, Kavlick, Mark F., Yoshimura, Kazuhisa, Rogers, Michael, LaFon, Steven, Manion, Douglas J., Lane, H. Clifford, Masur, Henry
• Format: Article
• Language: English
• Subjects: Abacavir; Adult; Amprenavir; Antiretrovirals; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacokinetics; Antivirals; Area Under Curve; Base Sequence; Benzoxazines; Biological and medical sciences; Carbamates; Clinical Articles; Dideoxynucleosides - administration & dosage; Dideoxynucleosides - pharmacokinetics; Drug Interactions; Drug Resistance; Drug Therapy, Combination; Efavirenz; Genetic mutation; Genotype; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - mortality; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human immunodeficiency virus; Human viral diseases; Humans; Infectious diseases; Male; Medical sciences; Middle Aged; Molecular Sequence Data; Mutation; Oxazines - administration & dosage; Oxazines - pharmacokinetics; Pharmacokinetics; Phenotype; Pilot Projects; Protease inhibitors; RNA, Viral - analysis; Sulfonamides - administration & dosage; Sulfonamides - pharmacokinetics; Treatment Outcome; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Viruses
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/313667

Patients with plasma viral RNA >50,000 copies/mL, despite a protease-inhibitor regimen, received abacavir, amprenavir, and efavirenz to assess efavirenz-amprenavir drug interactions and to evaluate safety and antiviral response. Patients first received amprenavir with abacavir and other nucleoside analogs. Amprenavir levels were measured before and after adding efavirenz. Patients then received a second protease inhibitor. There was evidence of genotypic and phenotypic resistance at study entry. No patient had study drugs discontinued because of toxicity. Efavirenz decreased the steady-state area under the curve, maximum plasma concentration, and minimum plasma concentration of amprenavir by 24%, 33%, and 43%, respectively. Three of 10 patients had >1.5 log10 viral response to abacavir and amprenavir. All 8 patients who added efavirenz had >0.5 log10 decline in viral load, and this response lasted >24 weeks for 3 of the patients. A combination regimen that included abacavir, amprenavir, and efavirenz was well tolerated and had sustained activity in some patients. Concomitant efavirenz therapy decreases amprenavir concentrations.