Dual Therapy Holds Its Own in Treatment-Naive HIV

MONTREAL -- A two-drug combination using a generic formulation of the protease inhibitor darunavir/ritonavir plus lamivudine appeared to control HIV as well as the same combination with added tenofovir, according to results of the phase IV ANDES trial reported here.

In the intention-to-treat analysis, 91% patients on the dual therapy achieved undetectable viral loads using the 50-copy assay at 48 weeks compared with 93% of those on triple therapy (P<0.01 for non-inferiority), said Maria Ines Figueroa, MD, of Fundacion Huesped in Buenos Aires, Argentina.

And in the per-protocol analysis, undetectable viral load rates were 98% and 99%, respectively (P<0.01 for non-inferiority), she noted.

In a post-hoc evaluation of patients with higher viral loads at baseline, about 90% of the patients on triple therapy achieved undetectable viral loads, compared with 87% of those on dual drug therapy, she added, explaining that the difference fell outside the criteria for non-inferiority.

"These results support [the] darunavir/ritonavir regimen as a potential therapeutic option for antiretroviral-naïve subjects, at least for patients with viral load below 100,000 copies/mL at baseline," she said at the International AIDS Conference.

"It is excellent to see the long-term outcomes with generic darunavir-lamivudine," said session moderator Chloe Orkin, MD, of Queen Mary's University London.

"The message here, really, is that an inexpensive medicine can have good results in treating people with HIV and that there is more than one two-drug therapy treatment aside from dolutegravir that can be used to maintain HIV suppression," she told MedPage Today. "It is an important finding."

The randomized open-label ANDES trial included 336 patients who had not previously received antiretroviral therapy, recruited from seven sites in Argentina. A total of 171 were assigned to receive dual therapy with darunavir 800 mg/ritonavir 100 mg in a fixed-dose combination plus lamivudine 300 mg, and 165 received triple therapy with the treatment plus tenofovir 300 mg.

The patients were a median 36 years old, and about 90% of the cohort were men. Median CD4-positive cell count was about 415 cells/mm³, although about 8% of the patients had CD4-positive cells counts below 200 cells/mm³, Figueroa reported.

About 93% of the patients enrolled in ANDES had CDC stage A disease, and about 23% had circulating HIV RNA of greater than 100,000 copies/mL.

A total of seven patients had virological failure: three on triple therapy, and four on dual therapy. Of the patients who experienced virological failure, three in the dual-therapy arm and two in the triple-therapy arm did not reach undetectable viral loads.

CD4-positive cell increase, a marker of immune system health, rose similarly in both groups, Figueroa reported. Those on triple therapy achieved an average 238 cells/mm³, while those on triple therapy saw an average rise of 275 cells/mm³ (P=0.442), a non-significant difference.

The dual-therapy strategy was "safe and well tolerated," she said. As was anticipated, grade 2/3 adverse events were higher in the triple-therapy arm (19% vs 12% with dual therapy, P=0.04). More abdominal pain was also cited by patients in the triple-therapy arm.

Lipid profiles and liver enzyme test abnormalities were similar for both arms of the trial, she reported.

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