Work

Persistent monocyte activation and remodeling in people with HIV after 36 months of switching from a 3-drug regimen to B/F/TAF or DTG/3TC: a sub-study of the DEBATE trial

Year: 2026

Type: article

Abstract: Introduction: The DEBATE study is a randomised trial comparing standard three-drug antiretroviral therapy (ART) with either a two-drug regimen (DTG/3TC) or an alternative three-drug regimen (B/F/TAF) in people with HIV who are virally suppressed. While these regimens are effective in controlling the virus, their impact on the innate immune system is less well understood. Monocytes play a pivotal role in inflammation by bridging innate and adaptive immunity and maintaining the viral reservoir. Persistent monocyte activation in individuals treated with ART, as indicated by altered subsets, proinflammatory cytokines and soluble markers, has been associated with chronic inflammation and non-AIDS comorbidities. This highlights the clinical relevance of monocyte activation even when viral suppression is achieved. Methods: Eleven virally suppressed people with HIV (PWH) randomized to switch to dolutegravir/lamivudine (DTG/3TC, n=6) or to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, n=5) were studied. Peripheral blood mononuclear cells (PBMC) collected at baseline and 36 months after the switch were analyzed using a 17-parameter flow cytometry panel to characterize monocyte phenotype. Results: Monocyte remodeling in chronically infected, ART-treated PWH involved chemokine receptors such as CX3CR1, CCR5 and CXCR4, which play important roles in cell migration, inflammation and viral reservoir maintenance. Moreover, the upregulation of TAM receptors (MerTK and Tyro3) and CD38 might enhance inflammatory effects in people switching to another three-drug regimen (3DR, B/F/TAF) rather than in those switching to a two-drug regimen (2DR, DTG/3TC). Nonetheless, in DTG/3TC-treated people, inflammation and viral reservoir maintenance might be promoted by the pSTAT3 pathway. Discussion: Persistent monocyte activation and immune senescence remain detectable in ART-experienced, virologically suppressed people with HIV after switching to either B/F/TAF or DTG/3TC, indicating that regimen optimization alone does not restore innate immune homeostasis. The enhanced expression of migratory and HIV-related receptors suggests ongoing reservoir maintenance and residual inflammation.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1957183