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BMC Infect Dis ; 16: 197, 2016 May 13.
Article in English | MEDLINE | ID: mdl-27177767

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.


Subject(s)
Drug Resistance, Viral/genetics , HIV Infections/drug therapy , HIV Integrase Inhibitors/therapeutic use , HIV-1/genetics , Raltegravir Potassium/therapeutic use , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , DNA, Viral/genetics , Female , Genotype , HIV Infections/virology , HIV Integrase/genetics , HIV-1/drug effects , Heterocyclic Compounds, 3-Ring/therapeutic use , Humans , Male , Middle Aged , Mutation , Oxazines , Pilot Projects , Piperazines , Pyridones , Retrospective Studies , Salvage Therapy , Treatment Failure , Viral Load/drug effects
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