Quadruple Nucleos(t)ide Reverse Transcriptase Inhibitors-Only Regimen of Tenofovir Plus Zidovudine/Lamivudine/Abacavir in Heavily Pre-Treated HIV-1 Infected Patients: Salvage Therapy or Backbone Only?

Christoph      Stephan; Brenda      Dauer; Pavel      Khaykin; Martin      Stuermer; Peter      Gute; Stephan      Klauke; Schlomo      Staszewski

doi:10.2174/157016209788348010

Abstract

Background: We investigated the virologic and immunologic responses to a mono-class, nucleoside/nucleotide reverse transcriptase inhibitor - combination therapy consisting of tenofovir and zidovudine/lamivudine/abacavir in therapy experienced patients. Methods: Retrospective study of 122 patients. Primary analysis was performed at 48 weeks. Virologic response was defined as viral load levels less than 400 copies/ml. Results: About half of the patients had switched to tenofovir+ zidovudine/lamivudine/abacavir for simplification purposes or toxicity while the other half had experienced virologic failure. 80/122 (66%) responded. Median viral load decreased to 78 copies/ml at week 48; median CD4 count increased to 321 cells/mm3. Of the 42 virologic failures, only 3 patients failed after week 24. 24/35 patients who had been on a non-suppressive zidovudine/lamivudine/abacavir-only regimen at baseline and added tenofovir to intensify, responded. 41/53 patients who switched from any nucleoside reverse transcriptase inhibitor-only regimen improved or maintained suppression. Genotypes were available for 85/122 patients. The only predictor of virologic failure was the combination 41L+210W+215Y/F mutational pattern.16 of the patients who failed on tenofovir+ zidovudine/lamivudine/abacavir therapy selected new primary nucleoside reverse transcriptase inhibitor resistance mutations that they previously did not have. 48/85 (56%) patients with genotype tests had at least 3 (3-10; median 4) nucleoside reverse transcriptase inhibitor resistance-associated mutations in the past. Conclusions: Patients heavily pre-treated with nucleoside analogues may show response to mono-class tenofovir+ zidovudine/ lamivudine/abacavir therapy despite having a history of failure with nucleoside reverse transcriptase inhibitors. Lower baseline viral load, higher baseline CD4 count were significant predictors for response. Archived 41L+210W+215Y/F mutational pattern was significantly associated with non-response.

Keywords: Tenofovir, Trizivir, Monoclass, NRTI therapy, Salvage therapy

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