Drug Interactions Among Anti-HIV Agents

HIV Infection Clinical Trial

Official title: Pharmacokinetic Interactions Between Ritonavir, Amprenavir and Efavirenz and Nelfinavir, Amprenavir, and Efavirenz in People Infected With HIV

Status Completed

Clinical Trial 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.

Clinical Trial Description

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, 6 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, ritonavir 500 mg po BID and efavirenz 600 mg po QD, and 10 with abacavir 300 mg po BID, amprenavir 1200 mg po BID, nelfinavir 1250 mg po BID and efavirenz 600 mg po QD. The groups enrolled sequentially: low-dose ritonavir combination group, then the full dose ritonavir combination group, and then the nelfinavir combination group. Subjects were seen at pre-entry, baseline (Day 1), and thereafter at study weeks 1 (serial sampling), 2 (serial sampling), 4, 8, 12, 16, 24 then every 8 weeks through one year. Patients discontinued current therapy and without a washout period began dosing. For the groups who will receive ritonavir, the schedule was: dose with abacavir and amprenavir and, after one-week, serial plasma sampling was performed for baseline amprenavir levels. Next ritonavir at the assigned dose was added (for the full-dose, there is a rapid dose escalation) and plasma sampling was repeated one week later; finally, efavirenz 600 mg once daily will be added and plasma sampling was again be repeated between 2 weeks after beginning the combination. For the nelfinavir group, the schedule was: dose with nelfinavir, amprenavir, and abacavir for one week and obtain serial plasma sampling, then add efavirenz for another week and obtain serial plasma sampling. Patients with a confirmed increase in viral burden of one log or greater from baseline will end study participation. The safety and antiviral activity of each combination were also assessed and continue to be assessed; toxicity management is outlined in the protocol. This study remains open in order to continue to provide these drugs to subjects who completed the original one-year study period and who wish to continue medications that appear, by viral load, to be of benefit to them. ;

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infection

• NCT number: NCT00001766
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 1
• Start date: August 1998
• Completion date: August 2003