Durability of Dolutegravir-Based Regimens: A 5-Year Prospective Observational Study.

none28noThis study evaluates the frequency and causes of dolutegravir (DTG) discontinuation along 5 years of follow-up, in both antiretroviral treatment (ART)-naive and experienced people living with HIV (PLWH). This is a prospective multi-center cohort study enrolling PLWH on DTG from July 2014 until November 2020. DTG-durability was investigated using the Kaplan-Meier survival curve. The Cox proportional-hazards model was used for estimating the hazard ratio (HR) of DTG discontinuation for any cause, and for adverse events (AEs). Nine hundred sixty-three PLWH were included, 25.3% were women and 28.0% were ART-naive. Discontinuations for any causes were 10.1 [95% confidence interval (95% CI) 8.9-11.5] per 100 person-years, similar in most regimens, with the apparent exception of tenofovir alafenamide/emtricitabine+DTG (p < 0.0001). In the multivariable Cox regression model, non-Caucasian ethnicity, age ≥50 years, and lower estimated glomerular filtration rate (eGFR) were associated with a higher probability of DTG interruption. The incidence rate of virological failure was 0.4 (95% CI 0.2-0.7) per 100 person-years, while the estimated discontinuation rate for AEs was 4.0 (3.2-4.9) per 100 person-years. Thirty-four DTG interruptions were due to grade ≥3 events (10 central nervous system, 6 hypersensitivity, 3 renal, 3 myalgia/asthenia, 3 abdominal pain, 2 gastrointestinal, and 7 other events). People with lower body mass index, age ≥50 years, and lower eGFR were at higher risk of AEs, while dual combinations were protective (HR 0.41 compared with abacavir/lamivudine/DTG, 95% CI 0.22-0.77). In this prospective observational study, we found high DTG durability and a low rate of virological failures. Dual therapies seemed protective toward AEs and might be considered, when feasible, a suitable option to minimize drug interactions and improve tolerability.mixedTaramasso L, De Vito A, Ricci ED, Orofino G, Squillace N, Menzaghi B, Molteni C, Gulminetti R, De Socio GV, Pellicanò GF, Sarchi E, Celesia BM, Calza L, Rusconi S, Valsecchi L, Martinelli CV, Cascio A, Maggi P, Vichi F, Angioni G, Guadagnino G, Cenderello G, Dentone C, Bandera A, Falasca K, Bonfanti P, Di Biagio A, Madeddu GTaramasso L, De Vito A, Ricci ED, Orofino G, Squillace N, Menzaghi B, Molteni C, Gulminetti R, De Socio GV, Pellicanò GF, Sarchi E, Celesia BM, Calza L, Rusconi S, Valsecchi L, Martinelli CV, Cascio A, Maggi P, Vichi F, Angioni G, Guadagnino G, Cenderello G, Dentone C, Bandera A, Falasca K, Bonfanti P, Di Biagio A, Madeddu