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Pediatric trials for ARV experienced children Coleen K. Cunningham

Pediatric trials for ARV experienced children Coleen K. Cunningham . Epidemiology of treatment experience in pediatrics How does the smaller number of HIV infected children as compared to adults impact on the type of trials that are feasible?

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Pediatric trials for ARV experienced children Coleen K. Cunningham

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  1. Pediatric trials for ARV experienced childrenColeen K. Cunningham • Epidemiology of treatment experience in pediatrics • How does the smaller number of HIV infected children as compared to adults impact on the type of trials that are feasible? • How does the management of HIV disease in children impact the type of trial design options as compared to adults? 1/11/01

  2. Pediatric HIV • Majority of HIV infected children are treatment experienced: in many cases multi-class experienced. • Evolution of treatment use in pediatrics: mono, dual and now heavy use of combinations • Decreased mortality: more of the infected children surviving years, decades • Few newly infected infants: limited new pool of treatment naïve young children 1/11/01

  3. Pediatric HIV • Majority of HIV infected children are treatment experienced: in many cases multi-class experienced. • Evolution of treatment use in pediatrics: mono, dual and now heavy use of combinations • Decreased mortality: more of the infected children surviving years, decades • Few newly infected infants: limited new pool of treatment naïve young children 1/11/01

  4. Pediatric HIV trends • Since anti-retroviral became available, we have struggled to determine optimal use in pediatrics. • AZT • AZT/ddI • AZT/3TC • d4T/ritonavir • 3 drug regimens- 1997 1/11/01

  5. Reported Rate (%) of Protease Inhibitor Use* among Subjects in PACTG 219 prior to Jan 1, 1996 *Protease inhibitor use since last PACTG 219 visit 1/11/01

  6. Pediatric HIV • Majority of HIV infected children are treatment experienced: in many cases multi-class experienced. • Evolution of treatment use in pediatrics: mono, dual and now heavy use of combinations • Decreased mortality: more of the infected children surviving years, decades • Few newly infected infants: limited new pool of treatment naïve young children 1/11/01

  7. Mortality Rates (% per year) among HIV infected subjects enrolled in PACTG 219 prior to Jan 1, 1996 Logrank test for trend significant P<0.0001 1/11/01

  8. Mortality Rates (% per year) by Race/ Ethnicity: HIV infected subjects enrolled in PACTG 219 prior to Jan 1, 1996 1/11/01

  9. Mortality Rates (% per year) by age among HIV infected subjects enrolled in PACTG 219 prior to Jan 1, 1996 1/11/01

  10. Pediatric HIV • Majority of HIV infected children are treatment experienced: in many cases multi-class experienced. • Evolution of treatment use in pediatrics: mono, dual and now heavy use of combinations • Decreased mortality: more of the infected children surviving years, decades • Few newly infected infants: limited new pool of treatment naïve young children 1/11/01

  11. Vertical transmission of HIV in PACTG studies: 1993-2000 076 185 316? Modified from Spector 10/00 1/11/01

  12. Pediatric HIV • Children with HIV are primarily treatment experienced, often multi-class experience and many saw sequential mono and dual nucleoside therapy • Exploring options for treatment experience children critically important for our patient population • Important to evaluate treatment options, management strategies and effectiveness of new agents in this group 1/11/01

  13. How do pediatric numbers impact on trial design? • How many HIV infected children are there? • Are they potentially available to participate in clinical trials? • What age groups are available? 1/11/01

  14. Children cared for at PACTG sites 1/11/01

  15. Racial/ethnic make up PACTG:NICHD 1/11/01

  16. How do pediatric numbers impact on trial design? • Biggest concern with numbers is treatment of naïve children. Numbers for that cohort very limited. Only studies that could be done would be very small and focused • Numbers of treatment experienced children much greater. Certainly, not the numbers that could be recruited for an adult study but definitely sufficient for efficacy trials using virologic endpoints. • Pharmacokinetics, safety, antiviral activity could all be done for a range of age groups. 1/11/01

  17. Treatment factors unique to pediatrics • Pharmacokinetics: vary with age, size, tanner staging • Must understand dosing for 2.5 kg, 4 weeks old through 100kg, 14 years old • Dosing: volume, palatability (have you tasted liquid ritonavir?), frequency (school schedules) • Toxicities: may be easier or more difficult for children to tolerate drugs; many seem better tolerated but what will long term sequelae be? (lipid abnormalities, mitochondrial toxicities) 1/11/01

  18. Treatment factors unique to pediatrics • Children generally dependant on an adult to deliver medicine • That adult may have limited ability to follow-through • Some parents feel guilty forcing their child to take foul tasting meds • Mother (or father) may be adjusting to treatment for their own disease • Children have frequent minor infectious illnesses that are common in childhood that can lead to intermittent dose intolerance or periodic treatment with additional medications (antibiotics for OM, for example). • Viral loads set-points are generally much higher in pediatrics. • CD4 counts are normally much higher in children 1/11/01

  19. Pediatric treatment trials • MUST run concurrent with adult trials • MUST have pediatric formulations available • PK, tolerability (including palatability), safety data are critical! • Need to understand long-term safety • Need to evaluate different management strategies 1/11/01

  20. Trial design options • Majority of US pediatric treatment trials have been carried out within the PACTG • PACTG has the scientific expertise and the patient base to carry out the trials • Currently, a large number of treatment experienced children are receiving care at PACTG or affiliated sites. 1/11/01

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