case discussion part i pediatric hiv treatment initiation รศ พญ ธันยวีร์...
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Case discussion part I Pediatric HIV treatment initiation
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25 กิรกิฎาคม 2556
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 ?
A 3 month old infant presented with interstitial pneumonia with respiratory failure Dx. PCP
ANC history: Mother HIV –ve at first trimester, Father: not testedVaginal 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
VOTE Now
What is your plan for HAART?
1 No HAART because CD4% > 25%
2 AZT + 3TC + NVP
3 AZT + 3TC + EFV
4 AZT + 3TC + LPV/r
Question
What is your choice for HAART?
Discussion
1 No HAART because CD4% > 25%
IncorrectShe has CDC “C”, Infant < 1 yr
2 AZT + 3TC + NVP IncorrectRecommend as alternative regimen due to higher rate of VL failure compare to LPV/r
3 AZT + 3TC + EFV IncorrectMay 2013: EFV was approved for >3 month and BW > 3.5 kg but no clinical trial data on efficacy in infant
4 AZT + 3TC + LPV/r Correct
Answer
LPV/r vs NVP in children < 3 years
PROMOTE paedsAchan 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 1Palumbo 2010
6 to 36 months of age who exposed to single dose NVP ( N=164) AZT + 3TC +NVP versus AZT+3TC+ LPV/rAt week 24, VL > 400 copies/ml or death or discontinue: 39.6% vs 21.7%
P1060 COHORT 2Violari 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.
2012 2013 2014
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
Clinical progression Age BW
(kg)CD4%
(CD4 count; cells/mm3)
HIV-RNA(c/ml)
HAART Remark
3 months 6 31 (1733) 2,600,000 AZT/3TC/LPV/r PCP
9 months 8 22 (2090) 402
1.5 years 9 31 (1623) < 50
2 years 12 34 (2500) < 50
3 years 14 32 (1100) < 50
Question
Shall we continue LPV/r-based HAART life-long?
1 Yes, this regimen is worked well – don’t bother to change
2 No, switch to NNRTI-based HAART to reduce metabolic complications
3 Not sure
VOTE Now
ANSWER
Shall we continue LPV/r-based HAART life-long?
1 Yes, this regimen is worked well – don’t bother to change
2 No, switch to NNRTI-based HAART to reduce metabolic complications
3 Not sure
Clinical progression Age BW
(kg)CD4%
(CD4 count; cells/mm3)
HIV-RNA(c/ml)
HAART Remark
4 months 6 31 (1733) 2,600,000 AZT/3TC/LPV/r PCP
9 months 8 22 (2090) 402
1.5 years 9 31 (1623) < 50
2 years 12 34 (2500) < 50
3 years 14 32 (1100) < 50 AZT/3TC/EFV
4 years 16 30 (990) < 40 AZT/3TC/EFV
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
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
VOTE Now
What is your plan for HAART?
1 No HAART because CD4 > 350 cell/mm3
2 AZT + 3TC + NVP (GPOvirZ)
3 d4T + 3TC +EFV
4 AZT + 3TC + EFV
5 ABC + 3TC + EFV
Question
What is your plan for HAART?
Answer
1 No HAART CD4 > 350 Incorrect: 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 +EFV Incorrect: should use only if anemia and then switch after 6-12 mo.
4 AZT + 3TC + EFV Correct: regarding Thai guideline however twice daily
5 ABC + 3TC + EFV Correct: once daily, but not provide by NHSO
Answer
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
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
VOTE Now
What is your plan for HAART?
1 No HAART: asymptomatic adolescent, concern about adherence
2 Give HAART only if have HIV negative partner
3 TDF + 3TC + EFV: standard once daily regimen
4 TDF + 3TC + ATV/r: TasP, lower chance for drug resistance
5 Patient-centered: ask the patient whatever he would like to do
Question
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
Risk of disease progression by CD45-year survival 5-year AIDS free survival
HIV-causal collaboration: Ann Intern Med 2011; 154:509-14
Mortality Hazard ratioCD4 < 350 cell = 1.01 (0.84-1.22)CD4 < 200 cell = 1.20 (0.97- 1.48)
AIDS-illness Hazard ratioCD4 < 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
Hazard ratio of tuberculosis by CD4 at time of initiation
Suthar AB. PLOS 2012; 9: e1001270
HR 0.43 (0.30-0.63)
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