Usefulness of Integrase resistance testing in proviral HIV-1 DNA in patients with Raltegravir prior failure

BMC Infectious Diseases

Research Article

María Dolores Mérida¹  David Vinuesa¹  José Hernández¹  Marta Álvarez¹  Federico García¹  Josefa López¹  Natalia Chueca¹  José Antonio Sánchez¹  María Ángeles Martínez¹  Jose Ángel Fernández-Caballero² 

[1] Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain;Complejo Hospitalario Universitario Granada. Servicio de Microbiología, Hospital Universitario San Cecilio. Instituto de Investigación Ibs. Granada, Av. Del Conocimiento s/n, 18016, Granada (Andalucía), Spain;Domicilio: C/Divan del Tamarit, 4, CP: 18198, Vega (Granada), Huetor, Spain;

关键词: HIV;    Integrase;    Proviral DNA;    Raltegravir;    Dolutegravir;   

DOI  :  10.1186/s12879-016-1545-8

 received in 2015-12-18, accepted in 2016-05-05,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundIn 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.MethodsWe 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.ResultsAll 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.ConclusionThis is a pilot study that demonstrates the possibility of properly identifying N155H and some secondary mutations 29–53 months after failure.

【 授权许可】

CC BY   
© Fernández-Caballero et al. 2016