TOPLINE:

Among treatment-naive people with HIV infection, the two-drug regimen dolutegravir/lamivudine (DTG/3TC) demonstrated comparable efficacy to the three-drug regimen DTG plus tenofovir alafenamide/emtricitabine (DTG+TAF/F) in reducing the HIV-1 reservoir and inflammatory marker responses and improving immune recovery over 24 months.

METHODOLOGY:

• Researchers conducted a phase 4, multicenter trial to evaluate whether the two-drug regimen DTG/3TC is as effective as the three-drug regimen DTG+TAF/F in reducing the viral reservoir, immune activation, and inflammation among treatment-naive people with HIV infection.
• They enrolled 66 people with plasma HIV-1 RNA levels > 5000 and < 500,000 copies/mL and CD4+ T lymphocyte counts > 200 cells/μL who were randomly allocated to receive either DTG/3TC or DTG+TAF/F.
• The primary endpoint was changes in HIV-1 DNA and RNA levels associated with CD4+ T cells at 12 and 24 months.

TAKEAWAY:

• Intact HIV-1 DNA levels in CD4+ T cells decreased similarly in both treatment groups, with total defective HIV-1 DNA showing comparable decay patterns.
• Both treatment groups exhibited equivalent reductions in activation and proliferation of CD4+ and CD8+ T cells during the first 6 months, which stabilized thereafter.
• Plasma levels of inflammatory markers, including interleukin (IL)-1 beta, IL-6, TNF alpha, interferon gamma, sCD14, and sCD163, showed significant and comparable decreases in both groups.
• Immune recovery, assessed as a ratio of CD4+ to CD8+ T cells, increased similarly in both groups.

IN PRACTICE:

“The results of this randomized clinical trial suggest no differences in HIV-1 reservoir decay in purified CD4+ cells in treatment-naive PHIV [people with HIV-1] starting DTG+TAF/F compared to DTG/3TC throughout a 2-year follow-up. Furthermore, there were no differences in phenotypic changes in CD4+ and CD8+, plasma inflammatory markers, or immune recovery,” the authors wrote.

SOURCE:

This study was led by Abraham Saborido-Alconchel, PhD, Institute of Biomedicine of Seville/Virgen del Rocio University Hospital/CSIC/University of Seville in Seville, Spain. It was published online on October 3, 2025, in Clinical Microbiology and Infection.

LIMITATIONS:

This study population was predominantly White men, with lower participation from women.

DISCLOSURES:

This study received support from ViiV Healthcare. Additional funding came from the Instituto de Salud Carlos III through the Subprogram Miguel Servet and PFIS contracts, co-financed by the European Regional Development Fund. Some authors reported receiving financial support from pharmaceutical companies, including Gilead Sciences, AbbVie, MSD, ViiV, and Janssen Cilag.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.