Transcript AIDS 2008 PowerPoint Template

DIONE – 24 week efficacy, safety, tolerability and
pharmacokinetics of DRV/r QD in treatment-naïve
adolescents, 12 to <18 years
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DRV/r is approved for the treatment of ARV-naïve (QD and BID) and
experienced HIV-1-infected adults (BID), and in ARV-experienced pediatric
patients aged 6 to <18 years (BID)
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DIONE is a Phase II, 48-week, open-label trial of once-daily DRV/r
800/100mg in combination with ZDV/3TC or ABC/3TC
Inclusion criteria
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Primary analysis at Week 24
Treatment-naïve adolescents, 12–<18 yrs
Weight 40kg
HIV-1 RNA 1000 copies/mL
DRV/r 800/100mg qd
+ ZDV/3TC or ABC/3TC
(site investigator-selected background regimen)
Enrollment
– 12 patients, mean age 14.6 years, eight female, mean log10 HIV RNA of
4.72 copies/mL and CD4 cell count of 282 cells/mm3/18.3%
– six received ZDV/3TC and six ABC/3TC
– five infected via MTCT and three via heterosexual contact
DRV/r = darunavir/ritonavir; ARV = antiretroviral; ZDV = zidovudine
3TC = lamivudine; ABC = abacavir; MTCT = mother-to-child transmission
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WEPDB0101
Response (± SE):
HIV-1 RNA <50 copies/mL
(ITT-TLOVR; %)
100
92%
80
60
40
DRV/r (N=12)
20
0
BAS 2
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4
8
16
Time (weeks)
Mean (± SE) change in CD4
cell count (cells/mm3) (NC=F)
Efficacy and safety findings
200
175
150
100
24
11/12 (92%) patients achieved HIV1 RNA <50 copies/mL (ITT-TLOVR)
12/12 (100%) by FDA snapshot
algorithm
One patient with one DRV RAM
(V11I) at baseline was a responder
at Week 24
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DRV/r (N=12)
50
0
BAS 2
4
8
16
Time (weeks)
24
Mean CD4 cell count increased by
175 cells/mm3
Two patients reported AEs at least
possibly related to treatment (all
grade 1 or 2)
No patient discontinued DRV/r due
to an AE
No deaths
SE = standard error; ITT = intent-to-treat; TLOVR = time-to-loss of virological response; NC=F = non-completer=failure
FDA = Food and Drug Administration; RAM = resistance-associated mutation; AEs = adverse events
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WEPDB0101
Pharmacokinetics
140
120
100
80
60
40
20
0
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4,000
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3,000
2,000
1,000
0
AUC
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Median: 2,196ng/mL
C0h (ng/mL)
AUC (µg•h/mL)
Median: 87.9µg•h/mL
C0h
Rich sampling over
24 hours after 2 weeks
of dosing
Grey dotted line represents
130%, 100% and 80%
(from top to bottom) of
mean observed in adults in
ARTEMIS1
DRV exposure similar to adults receiving DRV/r 800/100mg QD1
All had DRV C0h above EC50 for wild-type HIV (55ng/mL)
Conclusions
• Over 24 weeks, once-daily DRV/r 800/100mg (with two NRTIs) was effective
and well tolerated in ARV-naïve adolescents aged 12 to <18 years
• No new safety concerns were identified
• These findings support the use of once-daily DRV/r in treatment-naïve,
adolescent HIV-1-infected patients
1. Sekar V, et al. 9th IWCPHIV 2008. Abstract P42
AUC = area under the concentration-time curve; C0h = predose concentration; EC50 = effective concentration
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WEPDB0101