Pediatric Antiretroviral Therapy

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Pediatric Antiretroviral Therapy

• Katherine Knapp, MD
• St. Jude Childrens Research Hospital
• Memphis, Tennessee, USA
• December 3, 2003

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U.S. Pediatric HIV Treatment Guidelines

• Living Document available at http//AIDSinfo.nih
  .gov
• Working group of National Pediatric and Family
  HIV Resource Center (NPHRC), Health Resources and
  Services Administration (HRSA), National
  Institutes of Health (NIH)
• Last updated September 22, 2003

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1994 Revised CDC Classification for Pediatric HIV
Infection - Immunologic
MMWR, 1994 43 (No. RR-12) p.1-10
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1994 Revised CDC Classification for Pediatric HIV
Infection - Clinical
MMWR, 1994 43 (No. RR-12) p.1-10
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1993 Revision CDC AIDS Surveillance Case
Definition for Adolescents and Adults
persistent generalized lymphadenopathy
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Rationale for Timing of Therapy

• Treat early
• Suppress viral replication early
• Spare the immune system
• Prevent opportunistic infections (OIs)
• Reduce transmission
• Wait to treat
• Avoid toxicities of ART
• Avoid development of resistance
• Preserve future treatment options

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HIV-Infected Infant

• Recommendation Treat all children lt 12 months of
  age, regardless of clinical, virologic or immune
  status
• Infants at especially high risk of progression
• Unable to predict which infants will have faster
  disease progression
• However definitive clinical data lacking,
  concern about therapeutic levels in infants/high
  risk of developing resistance

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HIV-Infected ChildIndications for Treatment

• Symptomatic (CDC clinical categories A-C)
• Immune suppression (CDC immune categories 2 or 3)
• If asymptomatic with normal immune status two
  options
• Initiate therapy regardless
• Defer treatment if other factors favor
  postponement, monitor carefully

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HIV-Infected AdolescentTreatment Indications

• When initiating therapy in a post-pubertal
  adolescent, follow Guidelines for the Use of
  Antiretroviral Agents in HIV-Infected Adults and
  Adolescents
• Available at http//AIDSinfo.nih.gov
• Last updated November 10, 2003

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Current Commercially-Available Antiretroviral
Agents

• NRTI (7)
• zidovudine (ZDV)
• didanosine (ddI)
• zalcitabine (ddC)
• lamivudine (3TC)
• stavudine (d4T)
• abacavir (ABC)
• emtricitabine (FTC)
• NtRTI (1)
• tenofovir (TDF)
• Fusion Inhibitors (1)
• enfuvirtide (T-20)

• Protease Inhibitors (7)
• saquinavir (SQV)
• nelfinavir (NFV)
• indinavir (IDV)
• ritonavir (RTV)
• amprenavir (APV)
• lopinavir (LPV)
• atazanavir (AZV)
• NNRTI (3)
• nevirapine (NVP)
• delavirdine (DLV)
• efavirenz (EFV)

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Strongly Recommended

• Clinical trial evidence of clinical benefit
  and/or sustained suppression of HIV replication
  in adults and/or children
• One highly-active PI (NFV or RTV) plus two NRTIs
• Most data in children ZDV and ddI, ZDV and 3TC,
  d4T and ddI
• For children who can swallow capsules
• The NNRTI efavirenz (EFV) 2 NRTIs
• EFV NFV 1 NRTI

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Recommended as an Alternative

• Clinical trial evidence of suppression of HIV
  replication but
• Durability may be less or not defined, or
• Evidence of efficacy may not outweigh potential
  adverse consequences (e.g., toxicity, cost, drug
  interactions), or
• Experience in children is limited

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Recommended as an Alternative

• 2 NRTIs nevirapine (NVP)
• ZDV 3TC abacavir (ABC)
• 2 NRTIs lopinavir/ritonavir (LPV)
• 1 NRTI 1 NNRTI lopinavir/ritonavir
• For children who can swallow capsules
• 2 NRTIs indinavir (IDV)
• 2 NRTIs saquinavir (SQV)
• May be moved up to Strongly Recommended
  category with experience

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Offered Only in Special Circumstances

• Clinical trial evidence of either virologic
  suppression that is less durable, or data
  preliminary or inconclusive for use as initial
  therapy
• 2 NRTIs alone
• Amprenavir in combination with 2 NRTIs or ABC

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Not Recommended

• Evidence against use because of overlapping
  toxicity or use may be virologically undesirable
• Any monotherapy (infants on ZDV prophylaxis when
  diagnosed should change to combination therapy)
• d4T and ZDV (pharmacologic antagonism)
• ddC with one of the following ddI, d4T, 3TC

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Considerations When Choosing a Regimen

• Cost
• Potency, sustained response
• Frequency of dosing
• Side effects
• Preserving options for future regimens
• Tolerability, availability of liquid formulation,
  size of pills, number of pills

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Liquid Formulations

• Available
• ZDV, 3TC, ddI, d4T, ABC
• NVP
• NFV (powder), RTV, LPV/r
• Available through expanded-access
• EFV

Photo courtesy of Julie Richardson, PharmD
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Special Considerations with HIV Medications for
Children

• Liquid formulations not always available, not
  very palatable (high alcohol content), storage
  and shelf life requirements (30 days for ddI and
  d4T)
• Size of pills
• May start pill training at 4 years of age
• Importance of dedicated pharmacist, behavioral
  specialists

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Ways to Improve Palatability

• Refrigerate liquids
• Mix with milk, pudding, ice cream
• Dull taste buds first with ice, popsicle
• Coat the tongue with peanut butter
• Chase the meds with a strong taste cheeses,
  syrup, gum

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