Monitoring the emergence of resistance mutations in patients infected with HIV-1 under salvage therapy with raltegravir in Rio de Janeiro, Brazil: a follow-up study.
The present study describes a follow-up of a prospective and observational cohort of patients infected with HIV-1 and treated with raltegravir for salvage therapy in Brazil. Two groups of patients were analyzed: switching from T20 to RAL (Group 1, n = 9) and salvage therapy containing RAL (Group 2, n = 10). Blood samples were drawn for CD4(+) T-cell counts and HIV-1 viral load determinations. Protease, reverse transcriptase, and integrase genotyping were performed at baseline and at the time of virologic failure. CD4(+) T-cells increased at 6 and 12 months in both groups; HIV-1 viral load was continuously suppressed for Group 1, and for Group 2 it significantly decreased after starting a RAL-containing regimen. Three out of 10 patients from Group 2 could not suppress HIV-1 viral load. The mutations Q148H + G140S were observed for two patients and for the third patient only mutations to PR/RT inhibitors were detected. The genotypic sensitivity score (GSS) was analyzed for all patients of Group 2 and both patients who developed resistance to raltegravir presented a GSS < 2.0 for the RAL-containing scheme, which could be associated to the lack of effectiveness of the proposed scheme. The present study describes, for the first time in Brazil, the close follow-up of a series of patients using a raltegravir-containing HAART, showing the safety of the enfuvirtide switch to RAL and the effectiveness of a therapeutic regimen with RAL in promoting immune reconstitution and suppressing HIV replication, as well as documenting the occurrence of resistance to integrase inhibitors in the country.
Laboratory of AIDS and Molecular Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil. cpassaes@ioc.fiocruz.br
Caroline Pereira Bittencourt
CP
Passaes
Monick Lindenmeyer
ML
Guimarães
Sandra Wagner
SW
Cardoso
José Henrique
JH
Pilotto
Valdilea
V
Veloso
Beatriz
B
Grinsztejn
Mariza Gonçalves
MG
Morgado
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D001938:Brazil / Q000453:epidemiology; D018791:CD4 Lymphocyte Count; D003510:Cyclohexanes / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D000077560:Enfuvirtide; D005500:Follow-Up Studies; D060005:Genotyping Techniques; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D019427:HIV Integrase / Q000235:genetics; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics* / Q000502:physiology; D006801:Humans; D000077592:Maraviroc; D009154:Mutation; D010446:Peptide Fragments / Q000627:therapeutic use; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D000068898:Raltegravir Potassium; D016879:Salvage Therapy / Q000379:methods*; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011760:Pyrrolidinones; D012367:RNA, Viral; D014230:Triazoles; D000077560:Enfuvirtide; D000068898:Raltegravir Potassium; D019427:HIV Integrase; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; D000077592:Maraviroc