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M Cotton, H Cassim , N Pavía-Ruz , L Ross, S Ford, N Givens, K Cheng, J Sievers

TUAB0202. Pharmacokinetics, Safety and Antiviral Activity of Fosamprenavir/Ritonavir-Containing Regimens in HIV-Infected 4 Weeks to <2-Year-Old Children 48-Week Data From Study APV20002. M Cotton, H Cassim , N Pavía-Ruz , L Ross, S Ford, N Givens, K Cheng, J Sievers.

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M Cotton, H Cassim , N Pavía-Ruz , L Ross, S Ford, N Givens, K Cheng, J Sievers

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  1. TUAB0202 Pharmacokinetics, Safety and Antiviral Activity of Fosamprenavir/Ritonavir-Containing Regimens in HIV-Infected 4 Weeks to <2-Year-Old Children 48-Week Data From Study APV20002 M Cotton, H Cassim, N Pavía-Ruz, L Ross, S Ford, N Givens, K Cheng, J Sievers

  2. Lisa Ross, Susan Ford, Naomi Givens, Katharine Cheng, and Jörg Sievers are employees of GlaxoSmithKline. APV20002 is sponsored by ViiV Healthcare UK Limited and ViiV Healthcare Company. GlaxoSmithKline is responsible for implementing and managing all aspects of this study.

  3. Background • Several protease inhibitor (PI) therapies are approved for use in children • 6 are available in liquid formulation (USA) • 3 are approved in children <2 years of age (USA) • Need for increased treatment options for very young children • APV20002: PK, safety and antiviral activity of fosamprenavir (FPV)/ritonavir (RTV) BID in PI-naive and PI-experienced HIV-1–infected children 4 weeks to <2 years of age

  4. APV20002 Study Design • Phase II, open-label, 2-cohort, multicentre • Primary endpoints include: • Steady-state plasma amprenavir (APV) PK • AEs and laboratory abnormalities • Discontinuations due to AEs • No formal statistical hypothesis testing 4 weeks to <6 months FPV/RTV 45/10 mg/kg BID <2 years PI-naive/exp. HIV RNA ≥400 c/mL 6 months to <2 years FPV/RTV 45/7 mg/kg BID SDV Wk 24 Wk 48 Wk 2/8 8-12 hour PK

  5. Baseline CharacteristicsITT[E] Population

  6. Prior NRTI, NNRTI and PI Therapy

  7. Exposure to FPV/RTV BID • As of the data cutoff date for this 48-week analysis (5 July 2011): • Median exposure to FPV was 640 days (range 8-1093) • 78% were exposed for >48 weeks • 50% were exposed for >96 weeks • Ongoing study: 21 subjects remain enrolled

  8. Plasma APV AUC(0-)

  9. Plasma APV C

  10. Virologic Response and CD4+ Cell Percentage • Median increase in CD4+ cell percentages at Week 48 was 5% in both cohorts Snapshot analysis (MSD=F) 71% 64% 58%

  11. Virologic Failures • Overall, 9 subjects met analysis plan–defined virologic failure criteria • Virus from 3/9 had treatment-emergent resistance mutations • Full resistance profile in Poster MOPE0401 1. Ross et al. IAC 2012; Washington, DC. Abstract MOPE040.

  12. Adverse Events Safety Population • Most common AEs overall were diarrhoea (54%), gastroenteritis (36%), and upper respiratory tract infection (36%) • Drug-related Grade 2-4 AEs: a Includes one AE reported as “blood cholesterol.”

  13. Adverse Events (cont) Safety Population • 3 discontinuations due to treatment-emergent AEs: • Septicaemia, gastroenteritis, pulmonary tuberculosis • Overall, 22 subjects experienced serious AEs (SAEs) • 3 events were considered drug-related: • Gastroenteritis n=1 (2%) • Febrile convulsion n=1 (2%) • Transaminases increased n=1 (2%) • 3 subjects died following SAEs: • 24-month-old male: acute abdominal disorder • 19-month-old female: Grade 4 septicaemia • 2-month-old male: “muti” traditional medicine (herbal) poisoning and Grade 4 drug-related gastroenteritis

  14. Treatment-Emergent Grade 3/4 Laboratory Abnormalities—DAIDS 2004Observed Analysis

  15. Conclusions • Data support use of FPV/RTV in this young population: • Plasma APV exposures in infants aged 6 months to <2 years comparable to those from regimens approved in adults • Lower APV Cτ in infants <6 months of age but similar antiviral response in the two age groups • Overall safety profile similar to that observed in older children and adults • Another option for treatment with a PI in children in the US

  16. Acknowledgements We would like to thank all investigators, study personnel and patients who participated in this trial.

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