The Reverse Transcriptase (RT) Mutation V118I is Associated with Virologic Failure on Abacavir-based Treatment

Antiviral efficacy and serum lipids were investigated following a switch from long-term successful protease inhibitor based antiretroviral treatment (PI-ART) to abacavir (Ziagen)-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±265×10⁶/l to 798±366×10⁶/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 harbored 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, the authors write, “Viral failure was associated with prior mono- or dual-NRTI treatment and the occurrence of the V118I 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.”

06/25/04