Search

CD4+ regulatory T cells (Tregs) are essential for the maintenance of the immune system's equilibrium, by dampening the activation of potential auto-reactive T cells and avoiding excessive immune activation. To correctly perform their function, Tregs must be maintained at the right proportion with respect to effector T cells. Since this equilibrium is frequently disrupted in individuals infected with the human immunodeficiency virus (HIV), we hypothesize that its deregulation could hamper immune reconstitution in patients with poor CD4+ T cell recovery under highly active antiretroviral therapy (HAART). We analysed Tregs percentages amongst CD4+ T cells in 53 HIV-infected patients under HAART, with suppression of viral replication and distinct levels of immune reconstitution. As controls, 51 healthy individuals were also analysed. We observed that amongst the patients with Nadir values (the lowest CD4+ T cell counts achieved) <200 cells/µL, the individuals with high Tregs percentages (≥10% of total CD4+ T cells) had the worse CD4+ T cell reconstitution. In accordance, the well-described direct correlation between the Nadir value and CD4+ T cell reconstitution is clearly more evident in individuals with high Tregs proportions. Furthermore, we observed a strong negative correlation between Tregs percentages and CD4+ T cell recovery among immunological non-responder HIV+ individuals. All together, this work shows that high Tregs frequency is an important factor associated with sub-optimal CD4+ T cell recovery. This is particularly relevant for immunological non-responders with low Nadir values. Our results suggest that the Tregs proportion might be of clinical relevance to define cut-offs for HAART initiation. [ABSTRACT FROM AUTHOR]

Objective: Dolutegravir plus lamivudine (2-DR) is suggested as an initial and switch option in HIV-1 treatment. The aim of this study was to analyze the effectiveness, durability, and safety of 2-DR compared to bictegravir/emtricitabine/tenofovir alafenamide (3-DR). Patients and methods: This was an observational, ambispective study that included all treatment-naïve (TN) and treatment-experienced (TE) people living with HIV/AIDS (PLWH), who started 2-DR or 3-DR between 01 July 2018, and 31 January 2022. The primary endpoint was non-inferiority, at 24 and 48 weeks, of 2-DR vs 3-DR regarding the percentage of PLWH with viral load (VL)<50 and 200 copies/mL in TN (12% margin) and VL≥50 and 200 copies/mL in TE (4% margin). Durability of response and safety were also measured. Results: 292 PLWH were included (39 TN and 253 TE). In TN PLWH, non-inferiority was not achieved at 24 weeks (17; 95% CI -17 to 51 p = 0.348). By week 48, all PLWH on 3-DR maintained VL<50 copies/mL compared to 70% of PLWH on 2-DR although without reaching statistical significance (-33; 95% CI -60 to -10 p = 0.289). Non-inferiority was not achieved in TE PLWH either at 24 (0.4; 95% CI -9 to 10 p = 1) or at 48 weeks (4.5; 95% CI -0.5 to 9 p = 0.132). In TN, the risk of treatment discontinuation was similar between groups (HR: 0.31, p = 0.07); similar rates were also found in TE (HR: 1.3, p = 0.38). TE PLWH on 2-DR showed a better safety profile compared to 3-DR (p = 0.017). Conclusion: Our results did not show non-inferiority in terms of virological effectiveness. Additionally, durability and safety of 2-DR were confirmed to be similar to 3-DR. [ABSTRACT FROM AUTHOR]