The reverse transcriptase (RT) mutation V118I is associated with virologic failure on abacavir-based antiretroviral treatment (ART) in HIV-1 infection.
Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir-based ART in 29 patients who have been followed for 28 months thereafter. Virologic failure occurred within 3 months in 21% (6/29) of the patients, and abacavir hypersensitivity in 1 individual. The remaining 22 patients continue to have HIV RNA < 50 copies/ml after 28 months with a CD4 increase from 605 +/- 265 x 10(6)/l to 798 +/- 366 x 10(6)/l (p < 0.001). All virologic failing patients had been on long-term unsuccessful nucleoside reverse transcriptase inhibitor (NRTI) therapy before PI-ART as compared to 32% (7/22) of the virologic non-failing patients (p < 0.01). The viral strains from the virologic failing patients harboured 3-6 reverse transcriptase (RT) mutations, including the V118I mutation in 5/6 cases prior to PI-ART or at viral rebound. Only the V118I RT mutation was statistically more common among virologic failing than non-failing NRTI pretreated patients (p < 0.05). Stepwise multiple regression analysis for viral failure resulted in a model with only the V118I RT mutation entering the model (p < 0.01). The LDL cholesterol and triglyceride values decreased and the HDL cholesterol increased after the switch to abacavir-based ART (p < 0.01, p < 0.05, p < 0.05, respectively). In conclusion, viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V1181 RT mutation, persisting despite long term viral control. The selection process for patients suitable for treatment simplification to abacavir-based ART should contain a detailed antiretroviral treatment history.
Säberg
Pär
P
Venhälsan (Gay Men's Health Clinic), Karolinska Institute, Stockholm Söder Hospital, 118 83 Stockholm, Sweden.
Koppel
Kristina
K
Bratt
Göran
G
Fredriksson
Eva Lena
EL
Hejdeman
Bo
B
Sitbon
Gisela
G
Sandström
Eric
E
D000328:Adult; D015224:Dideoxynucleosides / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010597:Pharmacogenetics; D011336:Probability; D011446:Prospective Studies; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D012044:Regression Analysis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D018570:Risk Assessment; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D017211:Treatment Failure; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects; D000099227:Abacavir
D015224:Dideoxynucleosides; D012194:RNA-Directed DNA Polymerase; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir