DIONE – 24 week efficacy, safety, tolerability and pharmacokinetics of DRV/r QD in treatment-naïve adolescents, 12 to <18 years 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) 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 Enrollment –12 patients, mean age 14.6 years, eight female, mean log 10 HIV RNA of 4.72 copies/mL and CD4 cell count of 282 cells/mm 3 /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 WEPDB0101 Inclusion criteria Treatment-naïve adolescents, 12–<18 yrs Weight  40kg HIV-1 RNA  1000 copies/mL Primary analysis at Week 24 DRV/r 800/100mg qd + ZDV/3TC or ABC/3TC (site investigator-selected background regimen)

Efficacy and safety findings 11/12 (92%) patients achieved HIV- 1 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 Mean CD4 cell count increased by 175 cells/mm 3 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 BAS Response (± SE): HIV-1 RNA <50 copies/mL (ITT-TLOVR; %) Time (weeks) DRV/r (N=12) 92% BAS Mean (± SE) change in CD4 cell count (cells/mm 3 ) (NC=F) Time (weeks) DRV/r (N=12) 175 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 WEPDB0101

Median: 87.9µgh/mLMedian: 2,196ng/mL 4,000 2,000 3,000 1, Pharmacokinetics DRV exposure similar to adults receiving DRV/r 800/100mg QD 1 All had DRV C 0h above EC 50 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 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 ARTEMIS 1 AUC  AUC  (µgh/mL) C 0h C 0h (ng/mL) 1. Sekar V, et al. 9th IWCPHIV Abstract P42 AUC = area under the concentration-time curve; C 0h = predose concentration; EC 50 = effective concentration WEPDB0101