Dual therapy as good as triple therapy for treatment-naïve HIV

Dual therapy with the fixed-dose combination of darunavir/ritonavir plus lamivudine effectively controlled HIV as the same combination with tenofovir in treatment-naïve patients with HIV, according to the phase IV ANDES trial presented at AIDS 2022.

Session moderator Dr Chloe Orkin of Queen Mary University of London, UK said this is an important finding.  “It is excellent to see the long-term outcomes with generic darunavir-lamivudine.”

“The message is that an inexpensive medicine can have good results in treating HIV and that there is more than one two-drug therapy treatment aside from dolutegravir that can be used to maintain HIV suppression,”  she added.

Week 48 results

In the intention-to-treat analysis, 91 percent of patients on the dual therapy achieved undetectable viral loads at 48 weeks compared with 93 percent of those on triple therapy (p<0.01 for noninferiority). [AIDS 2022, abstract 7335]

“Our results support the darunavir/ritonavir regimen as a potential therapeutic option for antiretroviral-naïve subjects, at least for patients with a viral load of <100,000 copies/mL at baseline,” commented principal author Dr Maria Ines Figueroa from Fundacion Huesped in Buenos Aires, Argentina, during her presentation at AIDS 2022.

The trial included 336 patients who had not received previous antiretroviral therapy. They were recruited from seven sites in Argentina. One hundred seventy-one patients were assigned to receive dual therapy with darunavir 800 mg/ritonavir 100 mg in a fixed-dose combination plus lamivudine 300 mg whereas 165 others received triple therapy with the same combination plus tenofovir 300 mg.

The median age of the patients was 36 years, 90 percent were men. The median CD4-positive cell count was about 415 cells/mm³. About 8 percent had CD4-positive cell counts of <200 cells/mm³.

Ninety-three percent of the patients had CDC stage A disease, and 23 percent had a circulating HIV RNA of >100,000 copies/mL.

In the per-protocol analysis, 98 percent and 99 percent of patients on the dual therapy and triple therapy, respectively, achieved undetectable viral loads (p<0.01 for noninferiority).

A post hoc evaluation of patients with higher viral loads at baseline showed that 90 percent of the patients on triple therapy achieved undetectable viral loads, compared with 87 percent of those on dual drug therapy. The difference fell outside the criteria for non-inferiority, Figueroa explained.

Seven patients (three on triple therapy, and four on dual therapy) had a virological failure. Of these patients, three in the dual-therapy arm and two in the triple-therapy arm did not achieve undetectable viral loads.

A safe and well-tolerated option

CD4-positive cell increase, a marker of immune system health, increased similarly in both groups. Patients on triple therapy achieved an average of 238 cells/mm³, while those on dual therapy saw an average rise of 275 cells/mm³ (p=0.442), which is not a significant difference. “The dual-therapy was safe and a well-tolerated option,” Figueroa reported.

Grade 2/3 adverse events were higher in the triple-therapy arm (19 percent vs 12 percent with dual therapy, p=0.04). Lipid profiles and liver enzyme test results were similar in both arms.

Initial combination regimens for ART-naïve patients may have comparable efficacy but vary in pill burden, drug interactions, or side effects. Treatment should be tailored to the individual patient to improve adherence and treatment response.