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Switch to ATV/r + 3TC
ATLAS-M Study

2. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Design
Randomisation
1:1
Open-label
W48
W96
> 18 years
On ATV/r + 2 NRTI ≥ 3 months
HIV RNA < 50 c/mL > 6 months
CD4 > 200/mm3 > 6 months
No previous treatment failure on or resistance to ATV and/or 3TC
HBs Ag negative
ATV/r 300/100 mg QD + 3TC 300 mg QD
N = 133
Continuation ATV/r 300/100 mg QD + 2 NRTI
N = 133
Objective
Primary Endpoint: proportion without treatment failure at W48
Treatment failure: virological failure (the 1st of 2 consecutive HIV RNA levels > 50 c/mL or a single level > c/mL), any treatment modification or discontinuation, loss to follow-up, consent withdrawal, progression to AIDS, or death for any cause
Non-inferiority of ATV/r + 3TC (ITT-e and per protocol analyses) ; lower limit of the 95% CI for the difference = -12%, 80% power
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72:

3. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Baseline characteristics and disposition at W48
ATV/r + 3TC
N = 133
ATV/r + 2 NRTI
Median age, years 44 46
Female, % 16 25
Previous AIDS event, %
13.5
12.0
Baseline CD4/mm3, median
622
616
Nadir CD4/mm3, median
274
257
Duration of HIV RNA < 50 c/mL (months), median
23.5
20.8
Duration of ART prior to study entry (years), median
2.8
2.7
HCV co-infection, %
10.5
NRTI backbone, %
TDF + FTC/3TC
ABC/3TC
Other
79 19 2
Discontinued at W48, N (%)
13 (10%)
26 (20%)
Virologic failure / Adverse event
2 / 4
5 / 8
Withdrew consent / Lost to follow-up
2 / 5
7 / 4
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72:

4. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Efficacy Results (W48)
% free of treatment failure
Treatment failure
ATV/r + 3TC
ATV/r + 2 NRTI p
Total 14 27
0.042
Virologic failure 2 6
Adverse event (treatment related) 5
Adverse event (not treatment related) 3
Withdrew consent 7
Loss to F-U 4
Other 1
ATV/r + 2 NRTI
ATV/r + 3TC
≠ (95% CI)
9.8 (1.2 to 14.8)
100
89.5
79.7 20 40 60 80 %
90.1
79.8
ITT-e
Switch = failure
Per protocol
10.3 (1.7 to 18.9)
Virologic failure
Genotype and quantification of ATV levels in 2/2 ATV/r + 3TC and 5/6 ATV/r + 2 NRTI
No mutations on RT or PRO genes
Undetectable ATV levels (< 0.05 mg/L): 1/2 ATV/r + 3TC and 3/5 ATV/r + 2 NRTI
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72:

5. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Adverse events
ATV/r + 3TC
N = 133
ATV/r + 2 NRTI
Clinical adverse events of any grade, %
CNS Gastrointestinal
Skin and soft tissues
Urinary tract
Respiratory tract
Infections
Neoplasm
Bone
Other
2.3
4.5
3.0
3.8
6.0
9.0
6.8
9.8
0.8
15.0
Grade 3-4 clinical adverse events (none related to treatment), N 3 4
Renal colic 2
Osteopenia/osteoporosis
Emerging grade 3-4 laboratory abnormalities, %
Total cholesterol
LDL-cholesterol
Triglycerides
Total bilirubin
ALT
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72:

6. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Mean change in eGFR (CKD-EPI formula) at W48, mL/min/1.73 m2
ATV/r + 3TC
ATV/r + 2 NRTI p
All patients
+ 2
- 5
< 0.001
Patients on TDF at baseline
+ 3
Lipids
Significant increase in total cholesterol (p < 0.001), HDL-cholesterol (p = 0.001) and LDL-cholesterol (p = 0.047) in ATV/r + 3TC group, compared with ATV/r + 2 NRTI group
Adherence
Self-reported adherence not different between study arms
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72:

7. ATLAS-M Study: switch to ATV/r + 3TC
ARV-trial.com
ATLAS-M Study: switch to ATV/r + 3TC
Conclusion
Simplification to ATV/r + 3TC in virologically suppressed patients on ATV/r + 2 NRTI is non-inferior and superior in a post-hoc analysis as compared with the continuation of the previous triple therapy at 48 weeks
A significant beneficial effect of ATV/r + 3TC in the evolution of eGFR was also observed, particularly in subjects discontinuing TDF
In virologically suppressed patients on ATV/r + 2 NRTI who are not coinfected with hepatitis B virus, a switch to dual therapy with ATV/r + 3TC may be considered
ATLAS-M
Di Giambenedetto S. J Antimicrob Chemother 2017;72: