Effectiveness of first-line lamivudine/dolutegravir antiretroviral therapy in persons with HIV: real-life data from the ICONA Foundation cohort

Objectives: This analysis aimed to evaluate the rate of failure of first-line lamivudine/dolutegravir in a real-world setting and assess the effectiveness among people with HIV (PWH) at higher risk of suboptimal response. Methods: The study included PWH from the ICONA cohort who started first-line lamivudine/dolutegravir between 2016 and 2024. The primary endpoint was time to treatment failure (TF), defined as virological failure (VF, two consecutive HIV-RNA of >50 copies/mL >6 months after treatment initiation) or discontinuation due to toxicity/lack virological control/non-adherence or death for any cause. Secondary endpoints were time to treatment discontinuation for any reason (TD) and pure VF. Main exposures of interest were baseline CD4 and HIV-RNA, age, sex at birth and nation of birth. Standard survival analysis and Cox regression models were used. Results: Among 446 participants, after a median follow-up of 22 months, 4.3% (n = 19) experienced TF, the 3 year cumulative probability was 5.8% (95% CI: 2.9%-8.7%). Baseline CD4 count was associated with a 3-fold higher risk of TF, which decreased after adjustments. Higher viral loads (>100 000 copies/mL), age >50 years and foreign-born status were also associated with an increased risk of TF. No differences in TF according to sex at birth were found. By 3 years the probabilities of TD and VF were 13.4% (95% CI: 9.1%-17.6%) and 2.3% (95% CI: 0.19%-4.4%), respectively. Conclusions: In our real-world setting, the TF probability for first-line lamivudine/dolutegravir was below 6% at 3 years, lower than in randomized trials. Our data suggest that, as shown with other regimens, PWH starting lamivudine/dolutegravir with CD4 count of ≤200 cells/mm3, HIV-RNA of >100 000 copies/mL, older age or foreign-born status may be at higher risk of TF, though larger studies are needed to qualify the magnitude of the effect.