Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure
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Fernández-Caballero, José Ángel; Chueca-Porcuna, Natalia; Álvarez Alday, Marta; Merida, María Dolores; López, Josefa; Sánchez, José Antonio; Vinuesa García, David; Martínez Pérez, María Ángeles; Hernández Quero, José; García García, FedericoEditorial
Biomed Central
Materia
HIV Integrase Proviral DNA Raltegravir Dolutegravir
Date
2016Referencia bibliográfica
Fernández-Caballero, J. A.; et al. Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure. BMC Infectious Diseases, 16: 197 (2016). [http://hdl.handle.net/10481/49914]
Sponsorship
This study was funded by Fondo de Investigación Sanitaria (PI12/01053, PI15/00713), RD12/0017/006 (Plan Nacional de I + D + I, Fondo Europeo de Desarrollo Regional-FEDER).Abstract
Background: In our study, we have hypothesized that proviral DNA may show the history of mutations that emerged
at previous failures to a Raltegravir containing regimen, in patients who are currently undetectable and candidates to
simplification to a Dolutegravir containing regimen, in order to decide on once a day or twice a day dosing.
Methods: We have performed a pilot, observational, retrospective, non interventional study, including 7 patients
infected by HIV-1, all with a history of previous failure to a RAL containing regimen, that were successfully
salvaged and had reached viral suppression. A genotypic viral Integrase region study was available for each
patient at the moment of RAL failure. After an average (IQR) time of 48 months (29–53) Integrase resistance
mutations in proviral DNA were studied.
Results: All the patients were infected by HIV-1 B subtypes, with a mean age of 55 (range 43 to 56), originating
from Spain, and 4 were women. Median viral load (log) and CD4 count at the moment of the study on proviral
DNA was of 1.3 log cp/ml (range 0–1.47) and 765.5 cells/μL (range; 436.75–1023.75). The median time (IQR)
between previous failure to RAL and the study on proviral DNA was 48 (29–53) months. At Raltegravir failure,
N155H was detected in four patients, and other secondary mutations were detected in five patients (71.4 %). In
proviral DNA, N155H was detected by population sequencing in three patients (42.8 %), and UDS demonstrated a
9.77 % relative abundance of N155H in the remaining patient. Sanger sequencing correctly identified all the
secondary mutations.
Conclusion: This is a pilot study that demonstrates the possibility of properly identifying N155H and some
secondary mutations 29–53 months after failure.