Drug Interactions Among Anti-HIV Agents

• Status: Completed
• Trial end date: 2003-08-01
• Target enrollment: 0
• Participant gender: All

Summary

This study examined the interactions of various drugs used to treat HIV infection in order to design larger studies of possible combinations for people who continue to have high viral levels despite combination therapy.

HIV-infected patients 18 years of age and older who have a viral load of at least 500 copies/mL; who have received 20 weeks of protease inhibitor therapy, with the same protease inhibitors in combination therapy for the last 12 weeks; and who have never been treated with abacavir, amprenavir or efavirenz were enrolled.

All patients will receive 600 milligrams a day of efavirenz (a non-nucleoside reverse transcriptase inhibitor); 300 mg twice daily of abacavir (a nucleoside analog); and 1200 mg twice a day of amprenavir (a protease inhibitor). In addition to these drugs, six patients will receive 500 mg twice a day of ritonavir (a protease inhibitor); six patients will receive 200 mg twice a day of ritonavir; and 10 will receive 1250 mg twice a day of nelfinavir (a protease inhibitor).

Patients in the two ritonavir groups (500-mg and 200-mg dose groups) took abacavir and amprenavir for one week and then come to the clinic for blood tests to measure drug levels before taking their morning pills and at 1/2, 1, 2, 4, 8, and 12 hours after taking the medicines. They will then add ritonavir to their treatment regimen. After one week, they will return for blood tests as before. They will then add efavirenz to their regimen and had bloods drawn again after another 1 or 2 weeks.

Patients in the nelfinavir group took abacavir, amprenavir and nelfinavir for one week and then have blood sampling as described above for the ritonavir group. They will then add efavirenz to the regimen and repeat the blood tests again after another 1 or 2 weeks.

Participants are being seen in the clinic for follow-up only if they wish to continue to participate and if the regimen appears to offer clinical benefit.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Abacavir; Amprenavir; Efavirenz; Nelfinavir; Ritonavir

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.