SAN FRANCISCO-Two separate clinical trials have demonstrated that triple combination antiretroviral therapy maintains its superiority over double therapy in the extended treatment of HIV infection, although neither study included clinical morbidity as an endpoint.
In the first multicenter study (AIDS Clinical Trials Group Protocol-ACTGP 229), presented at the 35th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), 302 HIV-infected patients were randomly assigned to triple or double therapy for an initial period of 24 weeks.
Triple therapy consisted of the HIV protease inhibitor saquinavir(Drug information on saquinavir) (Hoffman-La Roche) and the two nucleoside analog reverse transcriptase inhibitors zidovu-dine (AZT, Retrovir) and zalcitabine(Drug information on zalcitabine) (ddC, Hivid), while double therapy consisted of saquinavir plus AZT or ddC plus AZT, said Ann C. Collier, MD, associate professor of medicine and head, AIDS Treatment Unit, University of Washington, Seattle.
Doses were as follows: saquinavir, 600 mg three times daily; AZT, 200 mg three times daily; and ddC, 0.75 mg three times daily, given orally.
The study included 302 patients, 279 of whom completed 24 weeks of therapy. The results showed that triple therapy raised CD4+ cell counts and lowered the level of circulating virus more than did either of the double therapy combinations, Dr. Collier said. Also, after 24 weeks, CD4+ cell counts had returned to baseline in 37% of those on saquinavir plus AZT and 55% of those on ddC plus AZT, compared with 31% of persons on the triple-drug regimen.
To evaluate the safety, tolerance, and antiviral efficacy of continued therapy with saquinavir in combination with one or two of the nucleosides, Dr. Collier said, 244 of the original 302 patients participated in a 24-week extension study.
Of these, 218 individuals were eval-uable at the end of the study. The three treatment regimens were fairly well tolerated, Dr. Collier noted, with only 19 patients leaving the study for reasons of drug-related toxicity.