麻豆传媒

AMSTERDAM -- A two-drug regimen controlled HIV as well as standard three-drug therapy in patients just starting treatment, a researcher said here.

In parallel randomized phase III trials, the integrase inhibitor dolutegravir (Tivicay) combined with lamivudine (3TC) was non-inferior to dolutegravir along with tenofovir and emtricitabine (Truvada), according to Pedro Cahn, MD, PhD, of Fundacion Huesped in Buenos Aires.

The investigators of the so-called GEMINI trials did not see any evidence of drug resistance emerging after 48 weeks of therapy, Cahn said at the , although patients will be followed for a total of 144 weeks to study the issue.

The three-drug treatment paradigm emerged in the early years of anti-HIV medications, when it was observed that resistance quickly developed with monotherapy and dual therapy. But newer drugs with high barriers to resistance have prompted researchers to rethink the common wisdom.

Last year the FDA -- a co-formulation of dolutegravir and rilpivirine, marketed as Juluca -- for patients whose HIV is already controlled using three medications.

The advantages of two-drug regimens, Cahn said, are fewer adverse effects, lower risk of drug-drug interactions, and potentially lower cost.

"Treatment for HIV is life-long, so reducing drug burden would be very welcome both for providers and patients," Cahn told reporters.

The possibility of taking two drugs rather than three "gives us a chance to simplify" treatment, commented Linda-Gail Bekker, MBChB, PhD, of the Desmond Tutu HIV Centre in Cape Town, South Africa.

"I think there are significant numbers of patients who find drug burden a problem," she told 麻豆传媒. "Fewer drugs, for many people, is an important concept." Bekker, who is president of the International AIDS Society, which sponsors the biennial conference, moderated a media briefing at which the results were discussed.

The two trials enrolled a total of 1,433 patients who had fewer than 10 days of previous HIV treatment, no evidence of pre-existing drug resistance, and a plasma viral load of between 1,000 and 500,000 copies of HIV RNA per milliliter.

The primary endpoint of the studies was the proportion of patients on each regimen who had a viral load below 50 copies/mL after 48 weeks of treatment.

On an intent-to-treat basis, where patients were included in the analysis after even a single dose of study drugs, Cahn said, both studies showed similar results -- two drugs were not inferior to three drugs.

When the outcomes were pooled, the investigators found that 91% of patients getting two drugs and 93% of those on three drugs had reached the 50-copy/mL cutoff after 48 weeks. The treatment difference in the pooled results was minus 1.7 percentage points, which was within the pre-defined non-inferiority margin.

Cahn said there was little difference in outcomes and dropout rates when patients were stratified by their baseline viral load, above and below 100,000 copies/mL.

Importantly, there was no treatment-emergent resistance in either arm of the studies, Cahn said.

Cahn noted that lamivudine is a well-known and generally well-tolerated medication and dolutegravir is a "clean drug" in terms of toxicity. On the other hand, tenofovir is known for bone and renal adverse events.

Overall, he told reporters, adverse events were "comparable" between the arms, he said, but as expected patients getting tenofovir had more renal and bone side effects than those on the two-drug regimen.

Dolutegravir/lamivudine is not yet approved but Cahn told 麻豆传媒 he would be "comfortable" using the combination as long as patients met the criteria used in the trials.

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