News From ICAAC: Antiretroviral Therapy
Joel E. Gallant, M.D., M.P.H.
With the International AIDS Conference in Vancouver only a recent memory, it was no surprise that there wasn't a great deal of news on antiretroviral therapy at ICAAC in New Orleans. Nevertheless, a number of important studies were presented at Monday's Late-Breaker session, including the CAESAR study, which demonstrated a clinical and survival benefit of 3TC, as well as a study confirming the safety and efficacy of combination therapy with ritonavir and saquinavir, and early studies of two promising new antiretroviral agents: 141W94, an investigational protease inhibitor, and DMP-266, a new non-nucleoside reverse transcriptase inhibitor.
The CAESAR Study
Dr. Julio Montaner presented preliminary results from the CAESAR study, a
multinational trial in which participants were randomized in a 2:1:1 fashion to
receive either 3TC, 3TC plus loviride (a non-nucleoside reverse transcriptase
inhibitor), or placebo, in addition to an AZT-containing regimen (AZT
monotherapy, AZT/ddI, or AZT/ddC) [Abstract LB-6*]. After 52 weeks on blinded
therapy, all participants were offered open-label 3TC and loviride. Primary
endpoints were progression to new AIDS events or death. Entry criteria included
a CD4 count between 25 and 250 cells/mm3.
More on the Ritonavir/Saquinavir Combination
It has been known for some time that ritonavir increases the bioavailability of saquinavir, but concerns over additive hepatotoxicity have kept this com-bination from being used clinically. Data presented at the international conference in Vancouver suggested that the combination was safe and effective. In New Orleans, Dr. Cal Cohen from the Community Research Initiative of New England presented results of a trial of combination therapy with ritonavir (RTV) and saquinavir (SQV) in patients with CD4 counts between 100 and 500 cells/mm3 who had no prior exposure to protease inhibitors [Abstract LB-7b]. After discontinuing nucleoside reverse transcriptase inhibitors, participants were assigned to receive one of four regimens:
Thirty patients were assigned to each group. Complete data were available
for groups A and B, while data for groups C and D were preliminary. Viral load
at baseline was approximately 4.5 logs.
141W94, a New Protease Inhibitor
Dr. Robert T. Schooley, from the University of Colorado Health Sciences
Center, presented data from a multicenter, open-label phase I/II dose escalation
trial examining the safety and efficacy of the investigational protease
inhibitor, 141W94 (Vertex GlaxoWellcome) [Abstract LB-7a]. The drug is felt to
have good bioavailability and a unique resistance profile, and it exhibits
synergy with nucleoside analog reverse transcriptase inhibitors.
DMP-266: A New NNRTI
Dr. Douglas Mayers presented data from a small trial examining the safety
and efficacy of DMP-266 (Dupont Merck), a new non-nucleoside reverse
transcriptase inhibitor (NNRTI) [Abstract LB8a]. Sixteen patients with CD4
counts between 200 and 500 cells/mm3 and HIV RNA > 20,000 copies/ml were
random-ized to receive either DMP-266 monotherapy (200 mg qd) or placebo.
Thirteen patients (81%) had received antiretrovirals previously, including one
who had received a protease inhibitor. After a period of two weeks, open-label
indinavir was added to both regimens.
*Abstract numbers refer to Abstracts of the 26th ICAAC, New Orleans, LA. Washington: American Society for Microbiology, 1996.