Background The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. Methods A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. Results 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1–90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6–99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. Conclusions In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen’s effectiveness.

BackgroundDolutegravir (DTG) plus lamivudine (3TC) has proven highly efficacious as a switching strategy in virologically suppressed people with HIV (PWH). As this strategy was introduced relatively recently, real‐world, long‐term durability studies are lacking.MethodsWe performed a retrospective review of treatment‐experienced patients who started DTG + 3TC in a cohort of PWH. HIV‐RNA <50 copies/mL was analysed at 144 weeks in an intention‐to‐treat (ITT) analysis (missing = failure) and a per‐protocol (PP) analysis (patients with missing data or changes for reasons other than virological failure were excluded).ResultsThe study population comprised 358 PWH (19% women). Median age and time with HIV infection were 51.7 and 13.4 years, respectively. The median number of previous antiretroviral combinations was three. Previous virological failure was reported in 27.1% of patients, and the M184V resistance mutation was detected in 17 patients. At 144 weeks, the percentage of individuals with HIV‐RNA <50 copies/mL was 77.4% (277/358) in the ITT analysis and 95.5% (277/290) in the PP analysis. A total of 68 participants were excluded from the PP analysis (data missing, 25, discontinuation due to toxicity, 19; other, 16; death, 8). Two people with virological failure selected resistance‐associated mutations (M184V and M184V + R263K). HIV‐RNA remained undetectable in 17 patients with a previous history of the M184V mutation.ConclusionOur results confirm the real‐world, long‐term efficacy, tolerability and high genetic barrier of DTG + 3TC in treatment‐experienced PWH. Although scarce, mutations causing resistance to nucleosides and integrase can emerge.