1. Switch to ATV/r monotherapy
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Switch to ATV/r monotherapy
ATARITMO
Swedish Study
ACTG A5201
OREY
MODAt Study 1

2. MODAt Study: switch to ATV/r monotherapy
Design
Randomisation*
1: 1
Open-label
W48
W96
≥ 18 years
Stable ATV/r + 2 NRTI ≥ 48 weeks with HIV RNA < 50 c/mL > 24 weeks
No previous virologic failure
CD4+ nadir > 100/mm3
No PPI or H2-receptor antagonists
HBs Ag negative
ATV/r 300/100 mg qd + 2 NRTI (continuation)
N = 51
ATV/r 300/100 mg monotherapy
N = 52
* Randomisation was stratified on HIV RNA (≤ or > c/mL) prior to ART start
Objective
Primary Endpoint: proportion with treatment success at W48
Treatment failure: treatment discontinuation for any cause or confirmed virologic rebound (first of 2 consecutive HIV RNA > 50 c/mL within 2 weeks)
Non-inferiority of ATV/r (ITT analysis) ; lower limit of the 2-sided 95% CI for the difference = -10% ; sample size = 342 (171 x 2), 80% power
Interim analysis by IDMC in June 2013: recommendation to stop further enrolment
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3. Baseline characteristics and disposition
MODAt Study: switch to ATV/r monotherapy
Baseline characteristics and disposition
ATV/r + 2 NRTI
N = 52
ATV/r monotherapy
N = 51
Female
14%
18%
Baseline CD4/mm3, median (IQR)
570 (417 – 735)
599 (457 – 774)
Nadir CD4/mm3, median (IQR)
278 ( )
274 (221 – 355)
Duration of HIV RNA < 50 c/mL (months), median 18 20
Duration on ATV/r + 2 NRTI (months), median 22
1st line antiretroviral therapy
71%
TDF/FTC backbone
85%
90%
Re-intensified before W48 with previous 2 NRTIs because of confirmed virologic rebound, N 11
Discontinued at W48, N 8 4
Adverse event 5 2
Confirmed virologic rebound -
Patient’s decision / lost to follow-up 1
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4. MODAt Study: switch to ATV/r monotherapy
Efficacy results
HIV RNA < 50 c/mL at W48 (ITT)
Confirmed virologic rebound
ATV/r
ATV/r + 2 NRTI
Sub groups
ATV/r + 2 NRTI
N = 52
ATV/r
N = 51 N 2 11
HIV RNA pre-ART > c/mL 1 6
Nadir CD4 < 350/mm3 9
HCV co-infection
Emergence of R mutations
1 (NRTI)
≠ (95% CI)
-12.1 ( ; 3.6)
100 85 73 92 20 40 60 80
44/ 52
37/ 51
47/ %
7.5 (- 4.7 ; 19.8)
Re-intensification
= failure
= success
Predictor of treatment failure in the ATV/r arm :
HCV co-infection (HR : 7.64 ; 95% CI: 1.44 to 40.47, p = 0.017)
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5. 1 arthritis + hyperuricemia 2 hematuria + proteinuria
MODAt Study: switch to ATV/r monotherapy
Safety, N (%)
ATV/r + 2 NRTI, N = 52
ATV/r, N = 51 p
Grade 3-4 clinical AEs
19 (36.5%)
6 (11.8%)
0.003
Grade 3-4 drug-related clinical AEs 6
2 nephrolithiasis
1 cholelithiasis
1 arthritis + hyperuricemia
2 hematuria + proteinuria
0.027
Change in total cholesterol (mg/dL) from baseline at W48, median
+ 1
+ 15
0.012
Grade 3-4 total cholesterol elevation 2
Change in LDL-cholesterol (mg/dL) from baseline at W48, median
- 9
+ 2
0.025
Grade 3-4 LDL-cholesterol elevation 3
Change in HLDL-cholesterol (mg/dL) from baseline at W48, median
+ 4
Grade 3-4 triglycerides elevation 1
Grade 3-4 hyperbilirubinemia
17 (33%)
20 (39%)
0.542
Change in eGFR at W48, median
0 ml/min/1.73m2
+ 6.2 ml/min/1.73 m2
0.155
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6. MODAt Study: switch to ATV/r monotherapy
Conclusion
ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy with ATV/r + 2 NRTI
Inferiority more pronounced in those with
Pre-ART HIV RNA > c/mL
Nadir CD4 < 350/mm3
HCV co-infection
No benefits of ATV/r monotherapy on lipids or renal function
NRTIs re-intensification was effective in all the individuals
The study was terminated early due to recommendation of IDMC
MODAt
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7. MODAt Study: switch to ATV/r monotherapy
W96 results
HIV RNA < 50 c/mL
ATV/r monotherapy = 64% vs ATV/r + 2 NRTI = 63%
Difference (95% CI): 1.3% (-17.5 to 20.1%)  monotherapy not non inferior
ATV/r monotherapy arm
Median HIV RNA at viral rebound (N=14): 136 (72–376) copies/mL;
No PI- or NRTI-associated resistance mutations were observed and all patients re-suppressed after reintensification
Drug-related adverse events leading to discontinuation: 3 (6%) in ATV/r monotherapy arm vs 11 (21.5%) in the triple-therapy arm (p = 0.041)
The 96 week adjusted mean percentage change in total proximal femur BMD was +1.16% and -1.64% in the ATV/r monotherapy arm and the triple-therapy arm, respectively (p = 0.012)
MODAt
Galli L. JAIDS 2016;71: