1. Comparison of PI vs PI ATV vs ATV/r BMS 089
ARV-trial.com
Comparison of PI vs PI
ATV vs ATV/r BMS 089
LPV/r mono vs LPV/r + ZDV/3TC MONARK
LPV/r QD vs BID M M A5073
LPV/r + 3TC vs LPV/r + 2 NRTI GARDEL
ATV/r vs FPV/r ALERT
ATV/r vs DRV/r ATADAR
FPV/r vs LPV/r KLEAN
SQV/r vs LPV/r GEMINI
ATV/r vs LPV/r CASTLE
DRV/r vs LPV/r ARTEMIS 1

2. ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
ARV-trial.com
ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
Design
Randomisation*
Open-label
N = 161
LPV/r 800/200 mg QD +
FTC 200 mg + (d4T-XR or TDF) QD
HIV-infected patients > 13 years
ARV-naïve or < 7 days prior ART
HIV RNA > 2,000 c/mL
Any CD4 cell count
N = 159
LPV/r 400/100 mg BID +
FTC 200 mg + (d4T-XR or TDF) QD
*Randomisation was stratified on HIV RNA < 100,000 c/mL or > 100,000 c/mL
The study had a third arm of LPV/r QD + FTC + (d4T-XR or TDF) administered by DOT in
82 patients, not included in the comparison of the 2 other arms.
Objective
Primary endpoint: Kaplan-Meier of sustained virologic response at W48
Sustained virologic response = lack of confirmed HIV RNA > 200 c/mL at W48 after confirmed HIV RNA < 200 c/ml ; or lack of confirmed HIV RNA > 200 c/mL at or after W24 ; lack of HIV RNA > 200 c/mL at W48 (no confirmation required)
Width of < 0.2 for the 2-sided 95% CI for the difference in probability of SVR
A5073
Flexner C. CID 2010; 50: 2

3. ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
ARV-trial.com
ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
Patient disposition and baseline characteristics
LPV/r QD
LPV/r BID
Mean age, years
39.3
38.2
Female
21%
23%
White/Black/Other
34% / 32% / 34%
27% / 36% / 37%
NRTI : d4T-XR / TDF*
62% / 38%
60% / 40%
HIV RNA (log10 c/mL), median
4.8
4.9
HIV RNA > 100,000 c/mL
51%
52%
CD4 cell count (/mm3), median
218
194
CD4 < 200/mm3
47%
53%
HCV Ab+
13%
Discontinuation before W48, n (%)
52 (32%)
41 (26%)
For toxicity 17 10
Virologic failure 36 29
* d4T-XR : 100 mg ; TDF : 300 mg
Note: LPV/r was administered as soft-gel capsules
A5073
Flexner C. CID 2010; 50: 3

4. ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
ARV-trial.com
ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
Estimated probability of sustained virologic response
(95% CI) at W48
LPV/r QD
LPV/r BID
Difference BID-QD
Intent-to treat
Overall
0.78 ( )
0.81 ( )
0.03 (-0.07 ; 0.12)
HIV RNA < 100,000 c/mL
0.80 ( )
0.72 ( )
( ; 0.06)
HIV RNA > 100,000 c/mL
0.76 ( )
0.89 ( )
0.13 (0.01 ; 0.25)
As-treated
0.85 ( )
0.00 (-0.09 ; 0.09)
0.86 ( )
0.80 ( )
-0.07 (-0.20 ; 0.07)
0.84 ( )
0.90 ( )
0.06 (-0.06 ; 0.17)
Regimen Completion*
0.61 ( )
0.66 ( )
0.05 (-0.05 ; 0.16)
* Virologic failure or discontinuation of initially randomised LPV/r schedule, whichever occurred first. No difference between groups, both overall and in each screening HIV RNA level stratum
A5073
Flexner C. CID 2010; 50: 4

5. ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
ARV-trial.com
ACTG A5073: LPV/r QD vs BID, in combination with FTC + (d4T-XR or TDF)
Emergence of resistance mutations to PI in virologic failure
Low incidence and no difference between QD (2/35 failure) and BID (3/26 failure)
Grade 3 or 4 clinical events and laboratory abnormalities
No significant difference in time to event between QD and BID
Adherence (electronic monitoring)
Significantly higher with QD during the first 24 weeks and between W24 and W48
Lopinavir Ctrough at week 16 and week 48
Significantly lower and more variable with QD
At W48, median Ctrough : 3.4 mg/mL for QD vs 5.6 mg/mL for BID
Conclusion
Overall, LPV/r QD and BID had similar outcomes
Patients with HIV RNA levels > 100,000 c/mL had better virologic response with LPV/r BID
A5073
Flexner C. CID 2010; 50: 5