1. Case discussion part I Pediatric HIV treatment initiation รศ พญ ธันยวีร์ ภูธนกิจ หน่วยโรคติดเชื้อ ภาควิชากุมารเวชศาสตร์ คณะ แพทยศาสตร์ จุฬาลงกรณ์มหาวิทยาลัย HIVNAT, ศูนย์วิจัยโรคเอดส์ สภากาชาดไทย thanyawee.p@hivnat.org thanyawee.p@hivnat.org 25 กรกฎาคม 2556

2. Pediatric Case Discussion Case 1: When and what to start in infant ? Case 2: When and what to start in children? Case 3: When and what to start in adolescents ?

3. A 3 month old infant presented with interstitial pneumonia with respiratory failure Dx. PCP ANC history: Mother HIV –ve at first trimester, Father: not tested Vaginal delivery, term BW 2,800 gm, breast feeding Mother and Father HIV antibody: positive Infant: CD4 31% (1733 cell/mm3) plasma HIV RNA: 2,600,000 c/ml Case I: 3 month old infant

4. VOTE Now What is your plan for HAART? 1No HAART because CD4% > 25% 2AZT + 3TC + NVP 3AZT + 3TC + EFV 4AZT + 3TC + LPV/r Question

5. What is your choice for HAART? Discussion 1No HAART because CD4% > 25% Incorrect She has CDC “C”, Infant < 1 yr 2AZT + 3TC + NVPIncorrect Recommend as alternative regimen due to higher rate of VL failure compare to LPV/r 3AZT + 3TC + EFVIncorrect May 2013: EFV was approved for >3 month and BW > 3.5 kg but no clinical trial data on efficacy in infant 4AZT + 3TC + LPV/rCorrect Answer

6. LPV/r vs NVP in children < 3 years PROMOTE paeds Achan 2012 3 mo- 6 year old children (median age 3.1 years, N= 185) NNRTI-based versus PI-based ART and followed for 6 months to 2 years. P1060 COHORT 1 Palumbo 2010 6 to 36 months of age who exposed to single dose NVP ( N=164) AZT + 3TC +NVP versus AZT+3TC+ LPV/r At week 24, VL > 400 copies/ml or death or discontinue: 39.6% vs 21.7% P1060 COHORT 2 Violari 2012 2-36 months old children who never exposed to single-dose NVP (N=288) NVP-based versus LPV/r-based ART. At week 24, VL > 400 copies/ml or death rate: 41.5% vs 19.4% Achan J. N Engl J Med 2012;367:2110-8; Palumbo P. N Eng J Med 2010; 363:1510-20; Violari A. N Engl J Med 012;366:2380-9.

7. LPV/r +2NRTIs granules clinical batch FINAL 4-in-1 Issue on drug formulation LPV/r syrup: refrigerated, poor taste Development of 4-in-1 capsule for young children by DNDi

8. Clinical progression AgeBW (kg) CD4% (CD4 count; cells/mm 3 ) HIV-RNA (c/ml) HAART Remark 3 months631 (1733)2,600,000AZT/3TC/LPV/rPCP 9 months822 (2090)402 1.5 years931 (1623)< 50 2 years1234 (2500)< 50 3 years1432 (1100)< 50

9. Question Shall we continue LPV/r-based HAART life-long? 1Yes, this regimen is worked well – don’t bother to change 2No, switch to NNRTI-based HAART to reduce metabolic complications 3Not sure VOTE Now

10. ANSWER Shall we continue LPV/r-based HAART life-long? 1Yes, this regimen is worked well – don’t bother to change 2No, switch to NNRTI-based HAART to reduce metabolic complications 3Not sure

11. Clinical progression AgeBW (kg) CD4% (CD4 count; cells/mm 3 ) HIV-RNA (c/ml) HAART Remark 4 months631 (1733)2,600,000AZT/3TC/LPV/rPCP 9 months822 (2090)402 1.5 years931 (1623)< 50 2 years1234 (2500)< 50 3 years1432 (1100)< 50AZT/3TC/EFV 4 years1630 (990)< 40AZT/3TC/EFV

12. Take home message HIV-infected infant has high plasma HIVRNA, the best option for treatment is LPV/r-based HAART Switch to NNRTI-based HAART as a maintenance therapy is encourage in a settings that HIV viral load monitoring is available. Take Home message

13. A 6-year old boy live with grandparents presented with poor growth, PPE, hospitalized due to pneumonia * 2 times in the past year BW = 18 kg, Ht = 105 cm Anti HIV: positive Hb: 9 mg/dl CD4: 18 % (400 cell/mm3) Case II: 6-year old boy

14. VOTE Now What is your plan for HAART? 1No HAART because CD4 > 350 cell/mm3 2AZT + 3TC + NVP (GPOvirZ) 3d4T + 3TC +EFV 4AZT + 3TC + EFV 5ABC + 3TC + EFV Question

15. What is your plan for HAART? Answer 1 No HAART CD4 > 350Incorrect: He has clinical category B AND CD4 between 350-500 cell/mm3 2 AZT + 3TC + NVP (GPOvirZ) Incorrect: NVP:Higher rate of VL failure 3 d4T + 3TC +EFVIncorrect: should use only if anemia and then switch after 6-12 mo. 4 AZT + 3TC + EFVCorrect: regarding Thai guideline however twice daily 5 ABC + 3TC + EFVCorrect: once daily, but not provide by NHSO Answer

16. Take home message HIV-infected children should initiate treatment when symptomatic: cat B, C regardless of CD4 and asymptomatic with CD4 < 500 cell/mm3 EFV has lower risk of virological failure than NVP Once daily regimen is preferred, however in Thailand; ABC is not yet widely available in the National program Take Home message

17. A 15-year old MSM sexually active for 1 year get tested for HIV as a routine check up Anti HIV: positive CD4: 24 % (480 cell/mm3) Case III: 15-year old MSM

18. VOTE Now What is your plan for HAART? 1No HAART: asymptomatic adolescent, concern about adherence 2Give HAART only if have HIV negative partner 3TDF + 3TC + EFV: standard once daily regimen 4TDF + 3TC + ATV/r: TasP, lower chance for drug resistance 5Patient-centered: ask the patient whatever he would like to do Question

19. HIV incidence in MSM cohort in Bangkok Griensvan F. AIDS 2013,27:825-32 Risk factors: younger age, living alone, drug use for pleasure, receptive anal intercourse, group sex

20. Risk of disease progression by CD4 5-year survival 5-year AIDS free survival HIV-causal collaboration: Ann Intern Med 2011; 154:509-14 Mortality Hazard ratio CD4 < 350 cell = 1.01 (0.84-1.22) CD4 < 200 cell = 1.20 (0.97- 1.48) AIDS-illness Hazard ratio CD4 < 350 cell = 1.38 (1.23-1.56) CD4 < 200 cell = 1.90 (1.67- 2.15) Number need to treat = 48 to prevent 1 AIDS event

21. Hazard ratio of tuberculosis by CD4 at time of initiation Suthar AB. PLOS 2012; 9: e1001270 HR 0.43 (0.30-0.63)

22. Take home message Behavioral risk HIV-infected adolescents will increase over the years, esp in MSM Decision to initiate ART should balance between disease progression risk/ risk of HIV transmission, and readiness of patient Should address adherence and risk of develop of drug resistance Once daily regimen with high genetic barrier might be an option. Take Home message