Pediatric HIV Update 2006 Evaluation and Treatment

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Pediatric HIV Update 2006
Evaluation and
Treatment
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Incidence of Perinatally-Acquired AIDS United
States, 1985-June 2000
Reported through December 2000
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ZDV Coverage Among HIV Pregnant Women July 98
June 2000 (n 918)
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Mean AZT coverage 69
80
60

1998 60
1999 72
2000 74
40
20
0
Jul
Jul
Jan
Jan
Chi square for linear trend p lt 0.001
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Antenatal Antiretroviral Treatment and Perinatal
Transmission in WITS, 1990-1999Blattner W. XIII
AIDS Conf, July 2000, Durban S Africa (LBOr4)
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Special Immunology Family Clinic
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Remaining U.S. Groups at Risk for Perinatal HIV
Transmission

• Late presenters without prenatal care
• Women seen in antenatal care but not offered
  voluntary counseling/testing due to perceived low
  risk
• HIV infected pregnant women who were prescribed
  but did not take antiretrovirals
• Unexplained failures

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Treatment case study 1 Pt AG

• 6 week old, born to mom on no treatment. First
  PCR and cx positive, repeat PCR positive.
• Initial CD41309
• Initial VL 480,000
• Discuss
• Treatment options
• US vs European vs WHO guidelines

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When to start therapy

• WHEN THE PATIENT IS READY!
• Assess
• home/school/family supports
• ability to swallow
• daily schedule
• patient/family belief in medications

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When to start HAART

• All infants- controversial
• All symptomatic infants/children/teens
• All infected children with viral load above-
  ?30,000, ?100,000
• All infected children with CD4 counts below-
  ?1000, ?500, ?300

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Antiretroviral Drug Approval 1987
2002From 2002-2006, additional 7 drugs
approved total of 23 now.
TDF
LPV/r
EFV ABC
APV
NFV DLV
RTV IDV NVP
3TC SQV
d4T
ddC
ddI
AZT
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Antiretroviral Agents
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ART combination agents
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ART Choice of NRTIall taste good, easy dosing,
bid or once daily
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ART Choice of NRTI combinations
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Choice of NNRTIeasy to take, minimal SE ,but
low barrier to resistance
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What to start

• For infants/young children
• NRTI backbone always consider using 3TC as
  one of the agents.
• ZDV long term safety good, minor manageable SE
  s anemia/neutro.
• d4T may have longer treatment efficacy than ZDV,
  but more toxicity (neuro and lipodystrophy)
• ddI liquid, poor tasting, SE s neuropathy,
  pancreatitis
• Tenofovir not available in liquid
• Abacavir risk of hypersensitivity

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What to start PI

• For infants, only choices are
• Nelfinavir-comes as a powder, or pills that can
  be crushed
• Kaletra-very potent, horrible tasting
• Ritonavir- horrible tasting
• For older children/teens, many choices.
• Consider treatments based on sequencing.

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Antiretroviral Agents
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What to start

• For infants/young children
• Limited choices based on poor palatability of
  many PI formulations
• ZDV/3TC/NVP/Abacavir- non PI regimen, relatively
  acceptable taste, about 5 tsps of liquid med, bid
• ZDV/3TC/Nelf- two liquids bid, 10 scoops of
  powder, 3x/dayneed to be careful on dosing
• ZDV/3TC/Kaletra-poor tasting, probably best data
  on efficacy over time.

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What to start

• For infants/young children
• Choosing PI vs NNRTI
• NNRTI better tasting, less frequent dosing, but
  much lower barrier to resistance.
• PI no good tasting choices, more frequent
  dosing, high barrier to resistance.
• In adults, starting with NNRTI based regimen
  appears to have better 2 yr results, but only
  slightly.

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Treatment case study 1 Pt AG

• After much discussion, started on
• ZDV/3Tc/Kaletra
• Post treatment results

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Response to Rx
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After much discussion, clear that mother was not
giving meds (resistance testing negative, drug
levelsnondetectable). Family services
involved, recruited father to give meds. Started
discussion about placing gtube. 16 weeks later,
VL undetectable, CD4 1261, 54. Viral load has
remained undetectable for 12months.
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Treatment case study 2 Pt WE

• 11 yr old,referred from outside hospital with
  lymph node biopsy MAI, recent HIV ab .
• CD4 1, viral load gt500,000
• Discuss
• Time to initiate HIV treatment
• Risk of immune reconstitution syndrome
• Interaction between MAI meds/ART
• Other prophylaxis

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Treatment case study 3 Pt TM

• Possible treatment regimens for older child/teen
• Trizivir one tab twice a day, no longer
  recommended. Single class regimen.
• Tenofovir/FTC/Sustivaone tab daily, NNRTI based.
• Combivir/Ritonavir/Atazanavir 4 tabs once a day,
  best once daily PI based regimen.
• Combivir/Kaletra 2 tabs twice day, best long
  term efficacy, GI SEs, major impact on lipids
  and ?lipodystrophy.

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Treatment case study 2 Pt WE

• Started on Rifab/Etham/Clarithro
• Started on Bactrim
• Initial HIV regimen
• Combivir Sustiva

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Pt WE response to treatment
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Treatment case study 3 Pt TM

• 10 yr old male, diagnosed upon maternal death
  from HIV.
• Never hospitalized.
• CD4 count 829/mm3
• Viral Load 6800 cpm
• Discuss timing of treatment, possible regimens

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What to start for school aged patients

• If the pt can swallow, several easy regimens
• Trizivir/Efavirenz one tab am, 2 tabsPM
• Combivir/Efavirenz- one tab am, 2 tabs bedtime
• Combivir/Nelfinavir-3 tabs BID, PI based
• For advance disease Combivir/Kaletra- 3 pills
  (2 very large) bid, plus TMP/SMZ if needed for
  low CD4.
• Tenofovir based regimens not approved for those
  lt18, no real pk data for smaller preteens
  

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What to start Sequencing

• Use of regimens with understanding of resistance
  patterns, so as to preserve future treatment
  options
• Example
• First round ZDV/3TC z NVP or Sustiva
• Second Tenofovir/FTC/Nelfinavir
• Third d4t/ddI/Atazanavir-Ritonavir
• Fourth Abacavir/ZDV/FTC and Kaletra or Lexiva or
  Daruanavir, Fuseon

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Treatment Case 3
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HAART THERAPY

• Changes over time in drug regimens
• 95-96 97-98 99-00
• Pts rx
• 0 meds 26 11 7
• 2 meds 49 13 7
• 3 meds 2 54 47
• 4 meds 0 20 38

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HAART- IMMUNOLOGIC BENEFIT

• CD4 95-96 97-98 99-00
• lt15 24 5 6
• gt25 53 69 72
• VL 97-98 98-99 99-00
• gt50,000 25 17 12
• lt400 17 32 43

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CARE OF THE HIV-INFECTED INFANT

• Prior to 1996 bimodal survival curve.
• 20-40 rapid progressors, ill by age 2, died by
  age 4
• 60-80 symptomatic by 5, average survival 8-10yrs
• At CHOP Yearly mortality prior to 1996 6.8
• From 1996-2001, no deaths. Since, yearly
  mortality of 1.

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ART- SIDE EFFECTS

• Hematologic
• Neutropenia- ZDV, 3TC, Abacavir
• Anemia- ZDV
• Pancreatitis
• ddI, d4T, HU
• Neuropathy
• ddI, d4T, HU

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ART- SIDE EFFECTS

• Lactic Acidosis
• any med, d4T most freq associated
• Hepatitis
• Ritonavir, nevaripine, abacavir

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ART- SIDE EFFECTS

• Lipodystrophy Syndrome
• Body changes- Buffalo hump
• Facial thinning
• Breast enlargement
• Abd. distention

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LIPODYSTROPHY SYNDROME

• Elevated Cholesterol and TG
• 1995-1996 1999-2000
• Mean chol. 131 193
• Mean TG 118 206

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ADHERENCE IS KEY

• In 1998, 40 of treatment courses failed
• Of treatment failures, 80 of families reported
  poor adherence, missing at least 20 of doses/week

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ADHERENCE IS KEY

• In 2000, of 100 patients
• 83 good adherence
• 8 fair
• 10 poor adherence

• 30 with VL lt400
• 50 with VL 400-20,000
• 12 with VL lt400
• None with VLlt400

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NO MORE IN 06

• Despite major therapeutic advances, the key to
  controlling the HIV epidemic will be through
  primary and secondary prevention.
• Next years infections, transmitted either
  through MCT or sexual contact, are virtually ALL
  preventable.
• Education, leading to sustainable changes in
  behavior, is the only way to quickly control this
  epidemic.