Drug Interactions Among Anti-HIV Agents

Launched by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES (NIAID) · Nov 3, 1999

Keywords

ClinConnect Summary

In this study of pharmacokinetic interactions, (1) the effect of ritonavir on the pharmacokinetics of amprenavir; (2) the effect of efavirenz on the pharmacokinetics of amprenavir and ritonavir, and (3) the effect of efavirenz on the pharmacokinetics of amprenavir and nelfinavir were examined. Twenty-two patients who have a viral burden of at least 500 copies/mL on combination therapy with a protease inhibitor for at least 20 weeks were to be enrolled to receive open-label treatment, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 200 mg po BID and efavirenz 600 mg po QD...

Gender

ALL

Eligibility criteria

• • INCLUSION
• • Adults (greater than 18 years) infected with HIV-1.
• • Plasma viral burden greater than 500 RNA copies/ml by bDNA method at screening visit while receiving a protease inhibitor as a part of combination therapy.
• • Treatment with a protease inhibitor or inhibitor(s) for the preceding 20 weeks with no protease inhibitor drug change or dose interruption for greater than 3 days in the most recent 12 weeks.
• Laboratory values at screen:
• • hemoglobin greater than 9 g/dl;
• • granulocyte count greater than 900 cells/microL;
• • platelet count greater than 80,000 cells/microL;
• • AST (SGOT) less than 151 U/L;
• • Creatine less than 2 mg/dL.
• • Willingness to avoid becoming pregnant or causing a pregnancy by use of effective methods which include surgical sterilization and barrier methods such as condoms and/or diaphragms. Hormonal methods of birth control are not acceptable unless barrier methods are also used because drug interactions may render their concentrations subtherapeutic.
• • Willing and able to provide written informed consent.
• • Negative serum or urine pregnancy test on the day of enrollment.
• • No intolerance of ritonavir or nelfinavir.
• • EXCLUSION
• • Treatment with systemic corticosteroids at greater than physiologic replacement doses, interleukins, interferons, radiation therapy or cytotoxic chemotherapeutic agents within 30 days of study drug administration or an anticipated need for radiation or chemotherapy treatment within the next 48 weeks (with the exception of local treatment for Kaposi's sarcoma).
• • Subjects suffering from serious medical conditions such as diabetes, congestive heart failure, cardiomyopathy, or other cardiac dysfunction, which, in the opinion of the investigator, would compromise the safety of the patient.
• • Current or anticipated therapy with other agents with documented activity against HIV-1 in vitro (other than stable maintenance dosing of foscarnet begun prior to screening).
• • Prior exposure to abacavir, amprenavir or efavirenz.
• • Concomitant therapy at entry with corticosteroids in other than replacement doses, chemotherapy, or investigational agents.
• • Active, untreated opportunistic infection or other major illness that would, in the opinion of the investigator, increase the risk that adverse events might pose to the patient or might render the patient too ill to return for study visits.
• • Lymphoma not diagnosed within 5 years of study enrollment.
• • Significant substance abuse or psychiatric illness that might interfere with assessment or compliance.
• • Refusal to employ adequate means of birth control (non-hormonal methods); efavirenz is potentially teratofenic and conception must be avoided.
• • Malabsorption or other gastrointestinal dysfunction which, in the opinion of the investigator, might interfere with drug absorption or render the patient unable to take oral medication.
• • History of serious rash (erythema multiforme or Stevens-Johnson syndrome) caused by nevirapine or delavirdine.
• • Treatment with phenobarbital, rifampin, rifabutin, midazolam, astemizole, cisapride, or triazolam unless subject is safely able to discontinue the drug(s) prior to receipt of study medications.
• • Pregnancy or lactation.