WASHINGTON — A new triple-therapy regimen for initial treatment of HIV-infected patients outperformed the conventional combination regimen in a preliminary 24-week analysis of a phase III trial with 509 patients.
If the results hold up for the study's prespecified 48-week duration, the new regimen “could change the standard of care,” Scott M. Hammer, M.D., said at the annual Interscience Conference on Antimicrobial Agents and Chemotherapy. “But 24-week data are too soon to judge,” added Dr. Hammer, chief of infectious diseases at Columbia-Presbyterian Medical Center in New York City.
The new regimen consisted of the nucleotide reverse-transcriptase inhibitor tenofovir (Viread), the nucleoside reserve-transcriptase inhibitor emtricitabine (Emtriva), and the nonnucleoside reverse-transcriptase inhibitor efavirenz (Sustiva). All three drugs were administered once daily, with tenofovir and emtricitabine combined into a single pill. The standard regimen that the new trio was compared against consisted of the nucleoside reverse-transcriptase inhibitors zidovudine (AZT) (Retrovir) and lamivudine (3TC) (Epivir), used in the single-pill formulation Combivir and administered b.i.d, along with efavirenz, given once daily.
The study, designed as a noninferiority trial, was sponsored by Gilead Sciences; Gilead markets both tenofovir and emtricitabine, as well as Truvada, the single-pill combination of 300-mg tenofovir and 200-mg emtricitabine. The study's primary end point was the time to loss of virologic response, an end point now required by the FDA for newly approved antiretroviral drugs. All five drugs included in the study are already approved as individual agents for use in the United States, and Combivir and Truvada also have FDA approval.
The edge that the new regimen had over the standard combination of zidovudine, lamivudine, and efavirenz seemed linked to tolerability and adherence. Among the 255 patients treated with tenofovir, emtricitabine, and efavirenz, 11% stopped taking their regimen during the first 24 weeks, compared with 21% of the 254 patients assigned to the standard regimen. The excess of dropouts was primarily due to adverse events, which led to 3% of patients stopping treatment in the tenofovir and emtricitabine arm, and 9% halting treatment in the zidovudine and lamivudine arm.
The most common adverse events in the zidovudine and lamivudine arm were anemia (5%), nausea, (2%), fatigue (1%), and vomiting (1%).
“The convenience and tolerability of an antiretroviral regimen is increasingly important, as patients remain on therapy for longer periods of time,” said Brian Gazzard, M.D., a physician at Chelsea and Westminster Hospital in London, who presented the results at the conference. “Although both triple-drug regimens are relatively convenient, we observed a difference in the two arms, with more patients discontinuing in the Combivir group due to adverse events.”
At 24 weeks, 87% of the patients treated with tenofovir and emtricitabine achieved and maintained a viral load of fewer than 400 copies of viral RNA/mL, and 73% achieved and maintained a viral load of fewer than 50 copies/mL. Among the patients treated with zidovudine and lamivudine, 78% maintained a viral load of fewer than 400 copies/mL, and 65% maintained a viral load of fewer than 50 copies/mL. The differences between the two regimens were statistically significant for both measures, Dr. Gazzard said at the conference, sponsored by the American Society for Microbiology.
Because the analyses were done on an intention-to-treat basis, with dropouts considered treatment failures, most of the difference between the two regimens was due to the difference in dropout rates.
Patients in the tenofovir and emtricitabine group also had a better immunologic response, gaining an average of 129 CD4 cells/μL, compared with an average gain of 111 cells/μL in the control arm, a statistically significant difference.
The two regimens showed no difference in the rate of emergence of drug-resistant virus.