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?
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/mm(3). 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.
Johann Wolfgang Goethe-University Hospital, HIV Treatment and Clinical Research Unit, Medical Department II, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. christoph.stephan@hivcenter.de
Christoph
C
Stephan
Brenda
B
Dauer
Pavel
P
Khaykin
Martin
M
Stuermer
Peter
P
Gute
Stephan
S
Klauke
Schlomo
S
Staszewski
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019943:Amino Acid Substitution / Q000235:genetics; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015224:Dideoxynucleosides / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D020125:Mutation, Missense; D063065:Organophosphonates / Q000627:therapeutic use*; D012189:Retrospective Studies; D016879:Salvage Therapy; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use*; D000099227:Abacavir
D000225:Adenine; D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D054303:HIV Reverse Transcriptase; D019259:Lamivudine; D063065:Organophosphonates; D000068698:Tenofovir; D015215:Zidovudine; D000099227:Abacavir; C514824:reverse transcriptase, Human immunodeficiency virus 1