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![Page 1: Indications for Initiation of ARV Therapy in Children Age >1 Year Clinical Category CD4 + Cell Percentage Plasma HIV RNA Copy Number Recommendation AIDS.](https://reader030.fdocuments.net/reader030/viewer/2022032606/56649ead5503460f94bb519c/html5/thumbnails/1.jpg)
Indications for Initiation of ARV Therapy in Children Age >1 Year
Clinical CategoryCD4+ Cell
Percentage
Plasma HIV RNA Copy
NumberRecommendation
AIDS (Clinical Category C)
OR
<15%
(Immune
Category 3)Any Value Treat
Mild-Moderate
Symptoms (Clinical Category
A or B)
OR
15–25%
(ImmuneCategory 2)
OR>100,000
copies/mL2
Consider
Treatment
Asymptomatic (Clinical
Category N)AND
>25%
(Immune
Category 1)
AND
<100,000 copies/mL2
Many experts would defer therapy and
closely monitor clinical, immune
and viral parameters
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Choice of Initial ARV Therapy
• Use ZDV monotherapy only for prophylaxis in indeterminate infant in first 6 weeks of life
• Use combination ARV therapy with at least 3 drugs
• Slows disease progression• Improves survival• Sustains virologic response better• Delays development of resistance
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Choice of Initial ARV Therapy
• Maximal suppression of viral replication to undetectable levels, if possible, for as long as possible
• Preservation or restoration of immune function
• Prevention of complications of HIV infection, including opportunistic infections
The goals of ARV therapy are:
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Choice of Initial ARV Therapy
• Consideration of resistance testing before initiation of therapy in newly diagnosed infants <12 months
• Particularly if mother has known or suspected drug-resistant virus
The Working Group recommends:
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Recommendations on ARV Regimens for Initial Therapy
• Data demonstrating durable viral suppression, immunologic and clinical improvement
• Incidence and types of drug toxicity
• Availability/palatability of formulations for children
• Dosing frequency, food and fluid needs
• Potential for drug interactions
Working Group criteria:
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Types of ARV Regimens for Children
• PI-based (2 NRTIs + PI)
• NNRTI-based(2 NRTIs + NNRTI)
• NRTI-based(3 NRTIs)
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Drug Regimen Categories for Initial Therapy
• Strongly recommended
• Recommended as an alternative
• Offered in special circumstances
• Not recommended
• Insufficient data for recommendation
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PI-Based Regimens
Advantages• Potent
• NNRTI-sparing
• Targets HIV at 2 steps
• Resistance requires multiple mutations
Disadvantages• High pill burden
• Multiple drug interactions
• Metabolic complications
• Poor palatability
• Few pediatric formulations
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Initial ARV Therapy:Recommended (PI-Based)
Strongly recommended:
Lopinavir/ritonavir or nelfinavir or ritonavir + 2 NRTIs1
Alternative recommendation:
Amprenavir (children >4 years old)2 or indinavir + 2 NRTIs1
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NNRTI-Based Regimens
Advantages
• Effective
• Palatable
• Less dyslipidemia/fat maldistribution
• PI-sparing
• Lower pill burden
Disadvantages
• Cross resistance among NNRTIs
• Rare, but serious life-threatening skin rashes
• Hepatic toxicity
• Multiple drug interactions
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Initial ARV Therapy:Recommended (NNRTI-Based)
Strongly recommended:
•Children >3 years:
Efavirenz3 + 2 NRTIs1
•Children <3 years or who cannot swallow capsules: Nevirapine3 + 2 NRTIs1
Alternative recommendation:
Nevirapine + 2 NRTIs in children >3 years old
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NRTI-Based Regimens
Advantages
• Spares other classes of drugs
• Minimal drug-drug interactions
• Limited NRTI cross resistance
• Palatable
• Lower pill burden
Disadvantages
• May be less potent than other regimens
• Rare, but serious lactic acidosis/hepatic steatosis
• Potential for ABC hypersensitivity
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Initial ARV Therapy:Recommended (NRTI-Based)
Strongly recommended:
None
Alternative recommendation:
Zidovudine + lamivudine + abacavir
Use only in special circumstances:
2 NRTIs1
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Initial ARV Therapy: Not Recommended
• Monotherapy—except ZDV prophylaxis for HIV exposed infants during the first 6 weeks of life
• Certain 2 NRTI combinations– Antagonistic: ZDV/d4T– Overlapping toxicities: d4T/ddC, ddI/ddC, 3TC/ddC– Similiar structure and identical resistance: 3TC/FTC
• Saquinavir: requires RTV boosting to achieve adequate drug level; pediatric dose unknown
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Initial ARV Therapy: Insufficient Data to Recommend
• Two NRTIs + delavirdine• Dual PIs (except lopinavir/ritonavir)• NRTI + NNRTI + PI (except EFV + NFV +
1 or 2 NRTIs)• Regimens containing
– Emtricitabine (FTC)– Tenofovir– Atazanavir– Fosamprenavir– Tipranavir/ritonavir– Enfuvirtide (T-20)
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11/26/03 AETC NRC 16
Changing ARV Therapy
• Failure based on virologic, immunologic, or clinical parameters
• Toxicity or intolerance on the current therapy
• Consider change if there is new data demonstrating that another regimen is superior to the current regimen
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Virologic Considerations for Changing ARV Therapy
• Less than 1.0 log10 decrease in HIV RNA from baseline 8-12 weeks after start of ARV therapy
• HIV RNA not suppressed to undetectable levels after 4-6 months
• Repeated detection in HIV RNA levels after undetectable levels on ARVs
• A reproducible increase in HIV RNA after substantial response
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Monitoring Virologic Response to Therapy Change
• Assess virologic response within 4 weeks after initiating or changing therapy
• Measure HIV RNA levels at least every 3 months
• Resistance testing is recommended for persistent or increasing HIV RNA levels
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• Change in immune classification• For children with <15% CD4+, persistent
decline of ≥5%• Rapid and substantive decrease in CD4+
count (ie, >30% decline in <6 months)
Immunologic Considerations for Changing ARV Therapy
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Clinical Considerations for Changing ARV Therapy
• Progressive neurodevelopmental deterioration
• Growth failure despite adequate nutritional support
• Disease progression
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Changing ARVs for Toxicity/Intolerance
• Choose drugs from same class with different toxicity/side effect profiles
• Change of a single drug is permissible if a single drug can be identified as a cause of toxicity
• Do not reduce dose below lower end of therapeutic dose range for the particular drug
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Changing ARVs for Treatment Failure/Disease Progression
• Assess and review adherence– Review patient medications
• Perform resistance testing– Consider overlap in resistance
• Change ARVs to contain at least 2 or 3 new ARVs
• Consider clinical trials of investigational ARVs• Discuss quality of life issues
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Adherence is Critical
• ARV most effective in initial therapy• Poor adherence may enhance drug
resistance• Child and caregiver participation is
crucial• Assess, discuss and address
adherence issues before initiating therapy
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Adherence Issues in Children
• Availability of drugs in palatable, liquid or mixable formulations
• Difficulty of giving drugs that have food restrictions, because of children’s (particularly infant) eating schedules
• Children’s dependence on caregivers for administration
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Adherence Issues in Children
• Timing issues, e.g., during school hours
• Families’ reluctance to disclose HIV diagnosis may limit medication administration at daycare/school
• Children’s developmental level influences ability and willingness to take medications
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Adherence Issues in Adolescents
• Denial and fear of their HIV infection
• Misinformation
• Distrust of the medical establishment
• Fear of ARV
• Lack of belief in the effectiveness of ARV
• Low self-esteem
• Unstructured and chaotic lifestyle
• Lack of familial and social support
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Adherence Issues in Adolescents
• Adolescents’ readiness
– Reminder systems, beepers, timers
– Stylish pill boxes
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Conclusion
Clinical care and treatment changes U.S. Pediatric Guidelines Working Group
meets monthly and reviews clinical trials result
Published text posted on www.aidsinfo.nih.gov Current slide set with speaker notes posted
on www.aidsetc.org