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

Abstract

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.

Figure 1.

Kaplan–Meier curves and estimated probabilities of TF at 1, 2 and 3 years among PWH initiating lamivudine/dolutegravir as first-line ART; overall (a), according to CD4 strata (b), HIV-RNA strata (c), age strata (d), nation of birth (e) and sex at birth (f).