August 11, 2008 (Mexico City) — The good news for heavily treatment-experienced patients and their physicians is that 3 recently approved drugs, when used in combination and with optimized background therapy, offer outstanding suppression of viral load. The aptly named TRIO study in France was presented in a late-breaker session here last week at the XVII International AIDS Conference.
The phase 2 noncomparative multicenter study enrolled heavily treatment-experienced patients (those who had a median of 13 years on therapy, 44% of whom had experienced an AIDS-defining event) who met the following criteria, explained Yazdan Yazdanpanah, MD, an investigator at the Tourcoing Hospital in France:
HIV RNA levels higher than 1000 copies/mL
no CD4 cell count restrictions
naive to raltegravir, etravirine, and darunavir
3 or more major protease inhibitor resistance mutations, but still susceptible to darunavir
3 or more nucleoside reverse transcriptase inhibitor mutations
previous virologic failure on nonnucleoside reverse transcriptase inhibitors, but susceptible to etravirine.
Of the 170 patients, the researchers found 67 to be ineligible; 19% of the 67 patients did not meet the HIV RNA threshold, and 67% did not meet the genotypic criteria. Enrollment consisted of 103 patients. Background therapy was optimized, and the standard approved doses of the drugs raltegravir, etravirine, and darunavir/ritonavir were added to the regimen.
Dr. Yazdanpanah presented an interim 24-week analysis of the ongoing study, which is projected to extend to at least 96 weeks. He said 90% of the patients achieved the principal endpoint of HIV RNA levels of less than 50 copies/mL. The median CD4 cell increase was +99 cells/mm3.
Of the 10 patients who did not achieve undetectable viral load at week 24, half had achieved it at an earlier time point and were hovering between that number and HIV RNA levels of less than 400 copies/mL. Of the remaining 5 patients, 1 was lost to follow-up, 1 withdrew as a result of a grade 4 adverse event (skin rash), 2 showed significant benefit, and 1 patient showed only modest benefit.
Dr. Yazdanpanah said they were able to add the 3 new drugs to this highly treatment-experienced population and that the combination was generally well tolerated. "We were able to demonstrate viral load suppression rates similar to those reported in antiretroviral treatment–naive patients."
During discussion, he was asked whether the researchers had examined the contribution of the optimized background therapy. He replied, "When you have 90% efficacy, it is difficult to do stratification. We looked, but it didn't make a difference."
"It is consistent with the BENCHMARK studies, where people who received darunavir and enfuvirtide did very well," said Richard Haubrich, MD, a researcher at the University of California, San Diego. "From the DUET studies, we know that etravirine is another potentially active agent, and this suggests that it is still active. So, having 3 active agents gives a good response."
He added, "The patients that didn't get [nucleoside reverse transcriptase inhibitors] — although only a few — did as well. [AIDS Clinical Trials Group] 5241 is looking at that; if you can add enough [active] agents, do you really need the [nucleoside reverse transcriptase inhibitors], or [optimized background therapy]?" Dr. Haubrich is cochair of that AIDS Clinical Trials Group study, which is hoping to simplify regimens in heavily treatment-experienced patients. Enrollment started in February 2008.
The TRIO study was supported by the Institut National de la SantÃ© et de la Recherche MÃ©dicale, or INSERM — a research agency of the French health ministry — with the support of pharmaceutical companies, which supplied the drugs. Dr. Yazdanpanah and Dr. Haubrich have disclosed no relevant financial relationships.
XVII International AIDS Conference: Abstract THAB0406. Presented August 7, 2008.
Medscape Medical News © 2008 Medscape
Cite this: Bob Roehr. TRIO of New HIV Drugs Leads to Undetectable Viral Load in 90% of Treatment-Experienced Patients - Medscape - Aug 11, 2008.