Lack of impact of protease inhibitor resistance-associated mutations on the outcome of HIV-1-infected patients switching to darunavir-based dual therapy
Por:
Vizcarra, P, Blanco, JL, Montejano, R, Negredo, E, Espinosa, N, Casado, JL, Monsalvo, M, Blanco, JL, Bernardino, JI, Puig, J, Montero, M, Castro, I, Mena, A, Castro, A, Palacios, R, de Quiros, JCLB, Tejerina, F, Latorre, LP, Ramirez, M, Vergas, J, Tellez, MJ, Galindo, P, Vilalta, RF, Cabello, A, Deltoro, MG, Cuevas, PR, de Santiago, AD and Moral, SD
Publicada:
3 mar 2020
Ahead of Print:
1 nov 2019
Resumen:
Background: Little is known about the impact of baseline resistance-associated mutations (RAMs) on the outcomes of alternative therapeutic strategies such as dual regimens. We assessed the efficacy of boosted darunavir plus raltegravir (DRV + RAL) dual regimen as a simplification strategy in virologically suppressed patients with protease inhibitors RAMs. Methods: Retrospective, multicentre study on the evolution of 228 heavily pretreated patients who switched to boosted DRV + RAL according to genotypic sensitivity score (GSS). Patients were classified as full susceptible (GSS = 2; n = 177), or with reduced darunavir susceptibility (GSS < 2; n = 51). Results: Median (range) number of prior antiretroviral regimens was 9 (6-14), with a median (range) of 2 (1-3), 4 (3-6), and 5 (2-9) major mutations to non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors, respectively. The median time of virological suppression before simplification was 49 months (IQR 39.8-63.5). Patients with reduced darunavir GSS showed a higher number of protease inhibitors-RAMs (9.3 vs 4.5, p < .01) and were suppressed for longer time (median, 61 months). At week 96, the rate of virological failure was low (two cases, 0.9%; 95% confidence interval, CI, 0.4-2.7%), and the efficacy, excluding non-virological reasons, was 96.8% (95%CI, 90.2-98.4%), without differences according to GSS or protease inhibitors-RAMs. Furthermore, significant improvements in CD4+ counts and CD4/CD8 ratio were observed (p < .01) in both groups. Conclusions: Treatment simplification to a dual regimen of boosted DRV + RAL after long-term virological suppression was not associated with a high risk of treatment failure, even in patients harbouring protease inhibitors-resistant HIV infection.
Filiaciones:
Vizcarra, P:
Hosp Univ Ramon y Cajal, IRYCIS, Dept Infect Dis, Madrid, Spain
Hosp Univ Ramon y Cajal, Madrid, Spain
Blanco, JL:
Hosp Clin Barcelona, Dept Infect Dis, Barcelona, Spain
Montejano, R:
Hosp Univ La Paz, Dept Internal Med, Madrid, Spain
Hosp Univ La Paz, Madrid, Spain
:
Hosp Univ Germans Trias I Pujol, HIV Unit, Badalona, Spain
Hosp Univ Germans Trias I Pujol, Lluita SIDA Fdn, Badalona, Spain
Hosp Univ Germans Trias i Pujol, Badalona, Spain
Espinosa, N:
Hosp Univ Virgen Rocio, Dept Infect Dis Microbiol & Prevent Med, Seville, Spain
Hosp Univ Virgen Roelo, Seville, Spain
Casado, JL:
Hosp Univ Ramon y Cajal, IRYCIS, Dept Infect Dis, Madrid, Spain
Hosp Univ Ramon y Cajal, Madrid, Spain
Monsalvo, M:
Hosp Univ Ramon y Cajal, Madrid, Spain
Blanco, JL:
Hosp Clin Barcelona, Barcelona, Spain
Bernardino, JI:
Hosp Univ La Paz, Madrid, Spain
:
Hosp Univ Germans Trias i Pujol, Badalona, Spain
Montero, M:
Hosp Univ La Fe, Valencia, Spain
Castro, I:
Hosp Univ La Fe, Valencia, Spain
Mena, A:
Complexo Hosp Univ A Coruna, La Coruna, Spain
Castro, A:
Complexo Hosp Univ A Coruna, La Coruna, Spain
Palacios, R:
Hosp Clin Univ Virgen Victoria, Malaga, Spain
de Quiros, JCLB:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Tejerina, F:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Latorre, LP:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Ramirez, M:
Hosp Gen Univ Gregorio Maranon, Madrid, Spain
Vergas, J:
Hosp Clin San Carlos, Madrid, Spain
Tellez, MJ:
Hosp Clin San Carlos, Madrid, Spain
Galindo, P:
Hosp Clin Univ Valencia, Valencia, Spain
Vilalta, RF:
Hosp Clin Univ Valencia, Valencia, Spain
Cabello, A:
Fdn Jimenez Diaz, Madrid, Spain
Deltoro, MG:
Hosp Gen Univ Valencia, Valencia, Spain
Cuevas, PR:
Hosp Gen Univ Valencia, Valencia, Spain
de Santiago, AD:
Hosp Univ Puerta Hierro, Madrid, Spain
Moral, SD:
Hosp Univ Puerta Hierro, Madrid, Spain
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