Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression.
BACKGROUND
Use of unboosted atazanavir (ATV400) is approved in the US but not in Europe (1). Due to pharmacokinetic interactions it should not be used with tenofovir but can be used with abacavir/lamivudine (ABC/3TC) (1, 2) (3). Effectiveness data of ATV400+ABC/3TC as a switch strategy in clinical routine however are scant.


METHODS
We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c/mL) and a snapshot analysis at 48, 96 and 144 weeks. Virological failure (VF) was defined as a confirmed plasma HIV-1 RNA >50 c/mL.


RESULTS
We included 258 subjects: 176 (68%) male, median age 46 (IQR 41, 53) y, 225 (87.2%) white, hepatitis virus co-infection 36%, median baseline CD4 at switch 540 cells (360, 700), time with VL≤ 50 c/mL 45 (24, 69) months. The median calendar year of switching was 2008 (2006, 2010). The 3rd drug in previous regimen was ATV/r in 70 (27.1%), other PI/r in 25 (9.7%), and other 163 (63.2%); 85 (32.9%) had previously failed with a PI. The virological response at 48/96/144 weeks was, respectively, 89.5 [95% CI 85.1, 92.9]/88 [83.4, 91.7]/86.3% [81.6, 90.4] (TLOVR, composite endpoint failure or stop for any reason) and the risk of VF was 8.3/7.6/7.6%. In the snapshot analysis HIV-RNA was below 50 c/mL in 72.5/65.9/51.6%, respectively, and >50 c/mL in 6.6/5.4/4.3%. Only 0.8/1.9/3.5% discontinued due to adverse events. There was a high rate of discontinuations due to other reasons or with VL missing in window. In a multivariate adjusted analysis, we observed an association between VF and nadir CD4 count (RH 0.60 [0.39, 0.93] per 100 cells higher), time with VL≤50 c/mL (RH 0.89 [0.81, 0.98] per 6 months longer) and previous failure with a PI (3.04 [1.36, 6.80]). There was no association with gender, age, hepatitis virus co-infection, CD4 count at time of switching or third drug used in the previous regimen.


CONCLUSIONS
A switch to ATV400+ABC/3TC in selected subjects with HIV-RNA below 50 c/mL is associated with relatively low rates of VF and discontinuation due to adverse events. Use might be considered in those with long-term suppression and without prior PI failure. Larger cohorts are required to further define the appropriate selection criteria.
HIV Unit, Hospital Germans Trias i Pujol/ Lluita contra la SIDA Fndn., Barcelona, Spain.
Josep M
JM
Llibre
Research Department of Infection & Population Health, University College London, London, UK.
Alessandro
A
Cozzi-Lepri
HIV Unit, Hospital Germans Trias i Pujol, Barcelona, Spain.
Jorge Antonio Valencia
JA
La Rosa
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
Court
C
Pedersen
Infectious Diseases, Helsinki University Central Hospital, Helsinki, Finland.
Matti
M
Ristola
Infectious Diseases, Hospital General de Agudos J. M. Ramos Mejía, Buenos Aires, Argentina.
Marcelo
M
Losso
Epidemiology and Medical Statistics, University College, London, UK.
Amanda
A
Mocroft
Infectious Diseases, Gomel State Medical University, Gomel, Belarus.
Victor M
VM
Mitsura
Infectious Diseases, Ullevål University, Oslo, Norway.
Vidar
V
Ormaasen
Infectious Diseases, Curry Cabral, Lisbon, Portugal.
Fernando
F
Maltez
Diagnostics and Therapy for AIDS, Specialistic Hospital, Chorzów, Poland.
Marek
M
Beniowski
IrsiCaixa Institute, IrsiCaixa Fndn, Barcelona, Spain.
Roger
R
Paredes