Late Breaker Session 7
A Randomized, Placebo-Controlled Trial of Saquinavir, Indinavir or Nelfinavir in Combination with Amprenavir, Abacavir, Efavirenz & Adefovir in Patients with PI Failure

• LB7: A Randomized, Placebo-Controlled Trial of Saquinavir (SQV)sgc, Indinavir (IDV) or Nelfinavir (NFV) in Combination with Amprenavir (APV), Abacavir (ABC), Efavirenz (EFZ) & Adefovir (ADV) in Patients (Pts) with Protease Inhibitor (PI) Failure (Authored by S. Hammer, J. Mellors, F. Vaida, K. Bennett, V. Degruttola, L. Sheiner and the ACTG 398 STUDY TEAM. NIAID-Sponsored AIDS Clin. Trials Group, Bethesda, MD)
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Scott Hammer, from Columbia Univ., presented the results of a large AIDS Clinical Trials Group (ACTG) salvage therapy trial, ACTG 398. This trial basically asked the question of whether a second protease inhibitor (PI), combined with APV (a PI), ABC, EFZ and ADV, would improve virologic response in protease inhibitor-experienced people with HIV RNA above 1,000.

A total of 481 people with one to three prior protease inhibitor exposures (SQV, IDV, RTV &/or NFV) were randomized, based upon prior protease inhibitor exposure, to 1 of 4 arms:

1. SQVsgc 1600 mg twice a day;

2. IDV 1200 mg twice a day;
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3. NFV 1250 mg twice a day; or

4. A second PI placebo.

Enrollment was also stratified by prior NNRTI exposure. All people received APV 1200 mg twice a day, ABC 300 mg twice a day, EFZ 600 mg once a day, and ADV 60 mg once a day (with L-carnitine).

A lot of data was presented, but the basic finding of the study, after 24 weeks, was that the people who received two new protease inhibitors did better than those who received just one new protease inhibitor. Also, people who had not received a NNRTI previously, did better than those who had previously received a NNRTI. The rate of serious side effects was similar in all arms of the study. One problem with this type of study is that we do not know the correct dosing of each drug, when so many new drugs are combined with each other. In this study, SQV lowered the blood levels of APV, but this did not appear to affect the outcome.

Dr. Hammer noted that, in conclusion:

1. HIV RNA suppression to less than 200 at 24 weeks was achieved in only 31% of people, despite 4-5 new agents.

2. Overall, the dual protease inhibitor arms were superior to the single protease inhibitor arm.

3. Prior NNRTI-exposure was significantly associated with higher treatment failure.

4. The high drop out rate observed in this study (33%) indicates that more effective and better tolerated salvage regimens are needed.