Monitoring the emergence of resistance mutations in patients under salvage therapy with Raltegravir in Rio de Janeiro, Brazil: a six month follow-up
Presented by Caroline Pereira Bittencourt Passaes (Brazil).
C.P.B. Passaes1, M.L. Guimarães1, S.W. Cardoso2, V. Veloso2, B. Grinsztejn2, M.G. Morgado1
1Oswaldo Cruz Foundation-FIOCRUZ, Laboratory of AIDS and Molecular Immunology, Rio de Janeiro, Brazil, 2Oswaldo Cruz Foundation-FIOCRUZ, Evandro Chagas Clinical Research Institute, Rio de Janeiro, Brazil
Background: Raltegravir (RAL) was approved to be used in the salvage therapy in Brazil in 2009. The aim of this work is to monitor the clinical parameters and the emergence of resistance mutations in the first four patients receiving a drug regimen containing RAL in the IPEC, in Rio de Janeiro, Brazil.
Methods: Samples were analyzed at baseline (T0), two (T1), and four/six (T2) months after initiating the therapy with RAL. CD4 and CD8 cells were measured by flow cytometry and viral load (VL) by the bDNA method. Plasma and blood samples were used to RNA and DNA extraction. The integrase genotyping was performed by an in house nested PCR, and samples were automatically sequenced. The analysis of resistance was performed based on the Stanford algorithm.
Results: After initiating RAL therapy, a modest, but consistent immune reconstitution was observed for all patients. VL levels greatly decreased for most patients, however, for two of them a rebound to higher levels (2 and 3log10) was observed at T2. RNA analysis evidenced the occurrence of virological failure (G140S/Q148H) at T2 for one of the 2 patients showing VL increase. In order to investigate if resistance mutations could be detectable in proviral DNA before their emergence in the plasma RNA, a total of 99 clones were analyzed from all visits. No major resistance mutations were detected in proviral samples, even in that sample presenting major resistance mutations. Some minor resistance mutations were observed in the DNA analysis: L74M;Q146H;Q95K;E138Q;M154I;G163R;S230N and R263K.
Conclusions: These results describe a case of early virological failure to RAL (four months). Major resistance mutations were not detected in the provirus. In spite of the emergence of resistant virus in 1 of the 4 individuals analyzed, RAL showed a good potential in suppress HIV VL and is a good option in the clinical management.
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