Emerging mutations at virological failure of HAART combinations containing tenofovir and lamivudine or emtricitabine.
OBJECTIVE
To compare the emergence of drug-resistant HIV variants at failure of lamivudine (3TC)/tenofovir (TDF)-containing or emtricitabine (FTC)/TDF-containing HAART as a consequence of the different 3TC and FTC intracellular half-lives.


METHODS
Retrospective evaluation of 859 patients selected from an Italian HIV resistance database (Antiretroviral Resistance Cohort Analysis).


METHODS
Patients were selected for analysis if treated with a HAART whose nucleoside/nucleotide reverse transcriptase inhibitor backbone was either 3TC/TDF or FTC/TDF; if they experienced a virological failure after at least 6 months of plasma HIV-RNA undetectability; and if HIV genotypes before treatment and at failure were available. Univariate and multivariate logistic regression analyses were done to detect predictors of resistance mutations emerging at failure.


RESULTS
Of 714 patients failing with 3TC/TDF and 145 with FTC/TDF, 35.8 and 21.1% were in Centers for Disease Control and Prevention stage C, and 8.8 and 15.2% were on first-line HAART, respectively. At multivariate analysis, the emergence of K70R (P = 0.002), M184V (P = 0.031), T215F (P = 0.020) and Y181C (P = 0.005) was significantly more common in 3TC-treated than in FTC-treated patients, with an odds ratio of 4, 1.56, 1.89 and 3.84, respectively.


CONCLUSIONS
Despite their close structural similarity, 3TC and FTC are associated with a significantly different rate of drug resistance at treatment failure when combined with TDF in HAART regimens independently of the third drug used.
Maserati
Renato
R
Department of Infectious Disease, Foundation IRCCS San Matteo Hospital, Pavia, Italy.
De Silvestri
Annalisa
A
Uglietti
Alessia
A
Colao
Grazia
G
Di Biagio
Antonio
A
Bruzzone
Bianca
B
Di Pietro
Massimo
M
Re
Maria Carla
MC
Tinelli
Carmine
C
Zazzi
Maurizio
M
D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D024882:Drug Resistance, Viral / Q000235:genetics*; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D009154:Mutation / Q000235:genetics; D063065:Organophosphonates / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D012189:Retrospective Studies; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
D019380:Anti-HIV Agents; D063065:Organophosphonates; D012367:RNA, Viral; D003841:Deoxycytidine; D019259:Lamivudine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine