A Randomized Trial of Dolutegravir Plus Darunavir/Cobicistat as a Switch Strategy in HIV-1-Infected Patients With Resistance to at Least 2 Antiretroviral Classes
Por:
Santos, JR, Domingo, P, Portilla, J, Gutiérrez, F, Imaz, A, Vilchez, H, Curran, A, Valcarce-Pardeiro, N, Payeras, A, Bernal, E, Montero-Alonso, M, Yzusqui, M, Clotet, B, Videla, S, Moltó, J, Paredes, R
Publicada:
1 nov 2023
Resumen:
Background. Suppressed patients with drug-resistant HIV-1 require effective and simple antiretroviral therapy to maintain treatment adherence and viral suppression.Methods. This randomized, open-label, noninferiority, multicenter pilot study involved HIV-infected adults who met the following criteria: confirmed HIV-1 RNA <50 copies/mL for >= 6 months preceding the study randomization, treatment with at least 3 antiretroviral drugs, and a history of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to darunavir (DRV) and integrase inhibitors. Participants were randomized 1:1 to switch to dolutegravir (DTG; 50 mg once per day) plus DRV boosted with cobicistat (DRV/c; 800/150 mg once per day; 2D group) or continue with their baseline regimen (standard-of-care [SOC] group). The primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%. Virologic failure was defined as confirmed HIV-1 RNA >= 50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation.Results. Forty-five participants were assigned to the 2D group and 44 to the SOC group. Time to loss of virologic response showed no difference in the proportion maintaining HIV-1 RNA <50 copies/mL at week 48: 39 of 45 (86.7%; 95% CI, 73.21%-94.95%) in the 2D group vs 42 of 44 (95.4%; 95% CI, 84.53%-99.44%) in the SOC group (log-rank P = .159) with an estimated difference of -8.7 (95% CI, -22.72 to 5.14). Only 2 (4.5%) in the SOC group experienced virologic failure, and 3 participants from the 2D group experienced adverse events leading to treatment discontinuation.Conclusions. In suppressed patients with at least 2 resistant antiretroviral classes, noninferiority could not be demonstrated by fully active DRV/c plus DTG. Nevertheless, there were no unexpected adverse events or virologic failure. DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients.
Filiaciones:
Santos, JR:
Hosp Univ Germans Trias i Pujol, Infect Dis Dept, Badalona, Catalonia, Spain
Hosp Univ Germans Trias i Pujol, Fundacio Lluita Infecc, Badalona, Catalonia, Spain
Hosp Univ Germans Trias i Pujol, Fundacio Lluita Infecc, Ctra Canyet S-N, Barcelona 08916, Spain
Domingo, P:
Hosp St Creu i St Pau, Serv Internal Med, HIV Unit, Barcelona, Spain
Gutiérrez, F:
Hosp Gen Univ Dr Balmis, Alicante, Spain
Hosp Gen Univ Elche, Dept Internal Med, Infect Dis Unit, Elche, Spain
Univ Miguel Hernandez, Alicante, Spain
CIBERINFEC ISCIII, Madrid, Spain
Imaz, A:
Hosp Univ Bellvitge, Infect Dis Serv, HIV Unit, Barcelona, Spain
Vilchez, H:
Hosp Univ Son Espases IdISBa, Internal Med Dept, Infect Dis Unit, Palma De Mallorca, Spain
Curran, A:
Hosp Univ Vall dHebron, Serv Infect Dis, HIV Unit, Barcelona, Spain
Valcarce-Pardeiro, N:
Complexo Hosp Univ Ferrol, Hosp Pharm, Ferrol, Spain
Payeras, A:
Hosp Son Llatzer, Serv Internal Med, Palma De Mallorca, Spain
Bernal, E:
Hosp Gen Univ Reina Sofia, Infect Dis Unit, Murcia, Spain
Inst Murciano Invest Biosanit, Murcia, Spain
Montero-Alonso, M:
Hosp Univ & Politecn La Fe, Infect Dis Unit, Valencia, Spain
Yzusqui, M:
Hosp Gen Nuestra Senora Prado, Dept Internal Med, Talavera De La Reina, Spain
Clotet, B:
IrsiCaixa AIDS Res Inst, Badalona, Spain
Videla, S:
Univ Barcelona, Sch Med & Hlth Sci, Dept Pathol & Expt Therapeut, Pharmacol Unit,IDIBELL, Barcelona, Spain
Lluita Infecc Fdn, Badalona, Spain
Moltó, J:
Hosp Univ Germans Trias i Pujol, Infect Dis Dept, Badalona, Catalonia, Spain
Hosp Univ Germans Trias i Pujol, Fundacio Lluita Infecc, Badalona, Catalonia, Spain
CIBERINFEC ISCIII, Madrid, Spain
Paredes, R:
Hosp Univ Germans Trias i Pujol, Infect Dis Dept, Badalona, Catalonia, Spain
Hosp Univ Germans Trias i Pujol, Fundacio Lluita Infecc, Badalona, Catalonia, Spain
IrsiCaixa AIDS Res Inst, Badalona, Spain
Case Western Reserve Univ, Ctr Global Hlth & Dis, Sch Med, Dept Pathol, Cleveland, OH USA
gold, Green Published
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