Efficacy of tenofovir and efavirenz in combination with lamivudine or emtricitabine in antiretroviral-naive patients in Europe.
BACKGROUND
The combination of tenofovir and efavirenz with either lamivudine or emtricitabine (TELE) has proved to be highly effective in clinical trials for first-line treatment of HIV-1 infection. However, limited data are available on its efficacy in routine clinical practice.


METHODS
A multicentre cohort study was performed in therapy-naive patients initiating ART with TELE before July 2009. Efficacy was studied using ITT (missing or switch = failure) and on-treatment (OT) analyses. Genotypic susceptibility scores (GSSs) were determined using the Stanford HIVdb algorithm.


RESULTS
Efficacy analysis of 1608 patients showed virological suppression to <50 copies/mL at 48 weeks in 91.5% (OT) and 70.6% (ITT). Almost a quarter of all patients (22.9%) had discontinued TELE at week 48, mainly due to CNS toxicity. Virological failure within 48 weeks was rarely observed (3.3%, n = 53). In multilevel, multivariate analysis, infection with subtype B (P = 0.011), baseline CD4 count <200 cells/mm³ (P < 0.001), GSS <3 (P = 0.002) and use of lamivudine (P < 0.001) were associated with a higher risk of virological failure. After exclusion of patients using co-formulated compounds, virological failure was still more often observed with lamivudine. Following virological failure, three-quarters of patients switched to a PI-based regimen with GSS <3. After 1 year of second-line therapy, viral load was suppressed to <50 copies/mL in 73.5% (OT).


CONCLUSIONS
In clinical practice, treatment failure on TELE regimens is relatively frequent due to toxicity. Virological failure is rare and more often observed with lamivudine than with emtricitabine. Following virological failure on TELE, PI-based second-line therapy was often successful despite GSS <3.
Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
J E
JE
Swartz
Department of General Internal Medicine, Ghent University, Ghent, Belgium.
L
L
Vandekerckhove
Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands.
H
H
Ammerlaan
Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands.
A C
AC
de Vries
Department of Infectious Diseases, University Hospital for Infectious Diseases, Zagreb, Croatia.
J
J
Begovac
Department of Internal Medicine, University Medical Centre Groningen, Groningen, The Netherlands.
W F W
WF
Bierman
Department of Virology, Erasmus MC, Rotterdam, The Netherlands.
C A B
CA
Boucher
Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands.
M E
ME
van der Ende
School of Public Health, Tel-Aviv University, Tel-Aviv, Israel.
Z
Z
Grossman
Institute of Virology, University of Cologne, Cologne, Germany.
R
R
Kaiser
School of Public Health, Tel-Aviv University, Tel-Aviv, Israel.
I
I
Levy
Department of Infectious Diseases, UMC Utrecht, Utrecht, The Netherlands.
T
T
Mudrikova
IrsiCaixa AIDS Research Institute, Hospital Universitari Germans Trias i Pujol, Badalona, Spain.
R
R
Paredes
Laboratory of Retrovirology, CRP Santé, Luxembourg, Luxembourg.
D
D
Perez-Bercoff
Department of Internal Medicine, Catharina Ziekenhuis, Eindhoven, The Netherlands.
M
M
Pronk
Department of Infectious Diseases, Rijnstate Hospital, Arnhem, The Netherlands.
C
C
Richter
Laboratory of Retrovirology, CRP Santé, Luxembourg, Luxembourg Department of Infectious Diseases, Centre Hospitalier de Luxembourg, Strassen, Luxembourg.
J C
JC
Schmit
Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
J
J
Vercauteren
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
M
M
Zazzi
Department of Infectious Diseases, University Hospital for Infectious Diseases, Zagreb, Croatia.
S
S
Židovec Lepej
Department of Infectious Diseases, Catholic University, Rome, Italy Infectious Diseases Unit, University Hospital of Siena, Siena, Italy.
A
A
De Luca
Department of Medical Microbiology, Virology, University Medical Center Utrecht, Utrecht, The Netherlands a.m.j.wensing@umcutrecht.nl.
A M J
AM
Wensing
D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D005060:Europe; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D016896:Treatment Outcome
D044966:Anti-Retroviral Agents
HIV-1; co-formulation; first-line antiretroviral therapy