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Integrase Inhibitor Reduces HIV Load and Is Well Tolerated: Presented at CROI

By Ed Susman

LOS ANGELES, CA -- March 2, 2007 -- The experimental integrase inhibitor elvitegravir (also known as GS-9137) at its highest dose level was able to significantly reduce HIV loads when compared with a protease inhibitor regimen, doctors reported here at the 14^th annual Conference on Retroviruses and Opportunistic Infections (CROI).

The phase 2, partially-blinded, randomised, active-controlled, phase 2 trial study tested 3 doses of GS 9137 -- 20 mg, 50 mg and 125 mg once a day -- all combined with an optimised background regimen, and compared the regimen to a protease inhibitor-based optimised background regimen in treatment-experienced patients whose virus had at least 1 protease resistant mutation.

In his presentation on February 28^th, Andrew Zolopa, MD, associate professor of medicine, Stanford School of Medicine, Stanford, California, United States, said that treatment with the 50-mg dose and the 125-mg dose both reduced circulating virus more effectively than the comparator therapy -- but only the 125 mg daily dose achieved statistical significance over the comparator (P = .02).

The 20 mg dose was ineffective and the study's Data Safety Monitoring Committee recommended that treatment with the 20-mg dose be stopped early in the trial because an excess number of patients in this treatment arm were unable to control viral replication.

Dr. Zolopa said the 24-week study was encouraging. "Integrase inhibitors represent a promising new class in the field of HIV treatment," he said. "As a clinician, I am frequently reminded of the importance of expanding simplified treatment options for people living with HIV, particularly among treatment-experienced patients who have developed resistance to many existing medications."

Integrase inhibitors are an investigational class of antiretroviral drug that interfere with HIV replication by blocking the ability of the virus to integrate into the genetic material of human cells.

Dr. Zolopa said the study will continue for 48 weeks.

For the study, the researchers randomised 278 to GS 9137 -- 71 patients to the 20-mg dose; 71 patients to 50 mg; 73 patients to 125 mg -- each also receiving 100 mg of ritonavir as a pharmacokinetic booster.

An additional 63 patients received an optimised background regimen of 2 or more nucleoside reverse transcriptase inhibitors with or without the fusion inhibitor enfuvirtide (T-20). These enfuvirtide patients were stratified across the treatment arms.

At study entry, patients were required to have an HIV viral load of at least 1,000 copies/mL and at least 1 protease resistance mutation. There was no CD4 cell count entry criterion for study participants.

The primary endpoint of the study was time-averaged change in HIV-1 RNA from baseline to week 24 (DAVG24).

Rapid and potent antiviral activity was observed in the 50 and 125 mg GS 9137 arms. Mean DAVG24 for patients receiving 50 mg of once-daily boosted GS 9137 was -1.4 log₁₀ copies/mL versus -1.2 log₁₀ copies/mL for the comparator arm (P = .27).

Mean DAVG24 for patients receiving 125 mg of once-daily boosted GS 9137 was -1.7 log₁₀ copies/mL versus -1.2 log₁₀ copies/mL for the comparator arm (P = .02).

Gilead Sciences, Foster City, California, developed GS 9137 and sponsored the study.


[Presentation title: The HIV Integrase Inhibitor GS-9137 Demonstrates Potent ARV Activity in Treatment-Experienced Patients. Abstract 143LB]

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