Download AII - AIDS Education and Training Centers

Guidelines for the Use of Antiretroviral Agents in
Pediatric HIV Infection
HHS Panel on Antiretroviral Therapy and
Medical Management of HIV-Infected Children – A Working
Group of the Office of AIDS Research Advisory Council
Slides prepared by:
François-Xavier Bagnoud Center, Rutgers School of Nursing
About This Presentation
These slides were developed using the Pediatric
Antiretroviral Guidelines, updated in March 2015. The
intended audience is clinicians involved in the care of
patients with HIV infection. For the complete text of the
guidelines, please visit: www.aidsinfo.nih.gov.
Because the field of HIV care is changing rapidly, users are
cautioned that the information in this presentation may
become out of date quickly.
Finally, it is intended that these slides be used as prepared,
without changes in either content or attribution. Users are
asked to honor this intent.
– AETC NRC
www.aidsetc.org
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Table of Contents
Topic







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Rating Scheme for Recommendations
Abbreviations
Identification of Perinatal HIV Exposure
HIV Diagnosis in Children
Clinical and Laboratory Monitoring
cART Initiation in Children
Pediatric cART Regimens
March 2015
Slide Number
5
6
10
15
30
39
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Table of Contents
Topic
 Considerations for Adolescents
 cART Adherence Issues
 Management of cART Toxicity or
Intolerance
 Modifying cART in Children to Promote
Sustained Viral Suppression
 Treatment Failure
 Discontinuation or Interruption of cART
 Therapeutic Drug Monitoring
 ARV Drug Resistance Testing
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Slide Number
69
73
84
88
91
104
106
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Rating Scheme for Recommendations
Strength of Recommendation
Quality of Evidence for Recommendation
A: Strong recommendation for the
statement
I: One or more randomized trials in children with clinical
outcomes and/or validated laboratory endpoints
B: Moderate recommendation for
the statement
I*: One or more randomized trials in adults with clinical
outcomes and/or validated laboratory endpoints with
accompanying data in children from one or more welldesigned, nonrandomized trials or observational cohort
studies with long-term clinical outcomes
C: Optional recommendation
II: One or more well-designed, nonrandomized trials or
observational cohort studies in children with long-term
clinical outcomes
II*: One or more well-designed nonrandomized trials or
observational cohort studies in adults with long-term
clinical outcomes with accompanying data in children
from one or more smaller nonrandomized trials or
cohort studies with clinical outcome data
III: Expert opinion
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Abbreviated Words
Antibody (Ab)
Antigen (Ag)
Antiretroviral (ARV)
Centers for Disease Control and Prevention (CDC)
Combination Antiretroviral Therapy (cART)
Directly Observed Therapy (DOT)
Enzyme Immunoassay (EIA)
Immune Reconstitution Inflammatory Syndrome (IRIS)
Integrase Strand Transfer Inhibitor (INSTI)
Modified Directly Observed Therapy (m-DOT)
Nucleoside/Nucleotide Analogue Reverse Transciptase Inhibitor (NRTI)
Non-Nucleoside Analogue Reverse Transciptase Inhibitor (NNRTI)
Opportunistic Infection (OI)
Pharmacokinetic (PK)
Polymerase Chain Reaction (PCR)
Protease Inhibitor (PI)
Viral Load (VL)
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Drug Abbreviations
NRTI
Abacavir (ABC)
Didanosine (ddI)
Emtricitabine (FTC)
Lamivudine (3TC)
Stavudine (d4T)
Tenofovir DF (TDF)
Zidovudine (AZT, ZDV)
PI
Atazanavir (ATV)
Darunavir (DRV)
Fosamprenavir (FPV)
Indinavir (IDV)
Lopinavir (LPV)
Nelfinavir (NFV)
Saquinavir (SQV)
Tipranavir (TPV)
NNRTI
Efavirenz (EFV)
Etravirine (ETR)
Nevirapine (NVP)
Rilpivirine (RPV)
Delavirdine (DLV)
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Fusion Inhibitor
Enfuvirtide (ENF, T-20)
CCR5 Antagonist
Maraviroc (MVC)
INSTI
Raltegravir (RAL)
Elvitegravir (EVG)
Dolutegravir (DTG)
Pharmacokinetic
Enhancers
Ritonavir (RTV, /r)
Cobicistat (COBI)
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Special Considerations in Pediatric cART
 Similar pathogenesis as well as virologic and
immunologic principles for cART apply to children,
adolescents, and adults with HIV infection
 Unique considerations in infants, children, and
adolescents exist
 For most children, infection transmitted via perinatal
exposure
 In utero, intrapartum, and/or postpartum neonatal
exposure to ARV drugs in most perinatally infected
children
 Diagnosis requires HIV virologic test for infants <18
months of age
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Special Considerations in Pediatric cART (2)
 Age-specific differences in interpreting CD4
counts
 Higher viral loads in perinatally infected infants
(compared with adults and adolescents)
 Changes in PK parameters with age
 Differences in the clinical manifestations and
treatment of HIV infection
 Special considerations associated with
adherence to ARV treatment in infants, children,
and adolescents
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Identification of
Perinatal HIV Exposure
Screening during Pregnancy
 HIV testing in early pregnancy is
recommended for all pregnant women in the
United States(AII)
 Repeat HIV testing in the 3rd trimester:
 Should be considered for all HIV-uninfected
pregnant women
 Is recommended for pregnant women who are
at high risk or reside in a high-prevalence area
(AIII)
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Screening in Labor and Delivery
 Rapid or expedited testing should be performed
during labor for women without documented HIV
status; immediately initiate intrapartum ARV
prophylaxis if screening is positive pending
confirmation results(AII)
 If acute HIV infection is suspected in a woman
whose HIV Ab is negative, a virologic test (eg,
plasma HIV RNA assay or combined Ag/Ab
immunoassay) should be performed(AII)
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Screening during Postnatal Period
 If no previous HIV results are available, offer
immediate rapid/expedited postpartum
maternal test or newborn HIV test(AII)
 If positive, initiate neonatal ARV prophylaxis
(preferably no later than 12 hours after birth)
and advise mother not to breast-feed pending
results of confirmatory testing
 If confirmation is negative and acute HIV
infection is ruled out, infant ARV prophylaxis
can be stopped
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Screening during Postnatal Period (2)
 Document results of maternal HIV testing in the
newborn medical record and communicate result
to the newborn’s primary care provider(AIII)
 Consider infant HIV Ab testing to determine
exposure status for infants in foster care and
adoptees if maternal status is unknown(AIII)
 Breast-feeding women with possible acute HIV
infection should stop breast-feeding immediately
until HIV infection is ruled out
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HIV Diagnosis in Children
Diagnostic Testing in Children with
Perinatal HIV Exposure
 Use virologic assays to diagnose HIV infection in
infants younger than 18 months(AII)
 HIV antibody (Ab) tests should not be used because
maternal HIV Abs may persist
 Two virologic tests from separate samples should be
used to confirm HIV infection
 Virologic diagnostic testing for infants with known
perinatal HIV exposure is recommended at ages
14-21 days, 1-2 months, AND 4-6 months(AII)
 HIV DNA and HIV RNA nucleic acid tests (NATs)
are recommended as the preferred virologic
assays(AII)
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Diagnostic Testing in Children with
Perinatal HIV Exposure(2)
 HIV DNA PCR
 Specificity: 99.8% at birth and 100% at 1, 3,
and 6 months
 Sensitivity: at birth 55% but >90% by 2-4
weeks, and 100% at 3 and 6 months
 Caution: the sensitivity and specificity of
noncommercial HIV-1 DNA tests may differ
from FDA-approved commercial tests
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Diagnostic Testing in Children with
Perinatal HIV Exposure(3)
 HIV RNA assays
 Specificity for results ≥5,000 copies/mL: 100% at birth,
1, 3, and 6 months of age
 RNA levels <5,000 copies/mL may not be
reproducible and tests should be repeated before they
are interpreted as documenting HIV infection
 Sensitivity: 25-58% during first weeks of life, 89% at 1
month, and 90-100% by 2-3 months
 HIV RNA can be used as a supplemental/confirmatory
test for infants with positive HIV DNA
 Less expensive and provides baseline HIV RNA
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Diagnostic Testing in Children with Perinatal HIV
Exposure(4)
Recommended
Testing with NAT
Diagnosis of
HIV infection
Consider at birth A positive
virologic test
for infants at
result should
high risk of
be confirmed
infection(AIII)
as soon as
Recommended possible by a
repeat
at ages below:
virologic test
• 14-21 days,
on a 2nd
• 1-2 months,
specimen(AII)
AND
• 4-6 months(AII)
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Definitive Exclusion of
HIV Infection
Two or more negative NATs at ≥1
month and ≥4 months(AII)
Consider additional NAT 2-4 weeks
after cessation of ARV prophylaxis if
prior NAT testing was negative while
the infant was receiving ARV
prophylaxis(BIII)
For non-breastfed infants ≥6 months
of age with no clinical or virologic
evidence of HIV infection, two
negative antibody tests from
separate specimens can also be
used to definitely exclude HIV
infection(AII)
March 2015
Additional
Testing
Some
experts
confirm the
absence of
HIV infection
at age 12 to
18 months
with an
antibody test
to document
loss of
maternal
HIV Abs(BIII)
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Diagnostic Testing in Children with
Perinatal HIV Exposure(5)
 Additional testing after cessation of ARV
prophylaxis should be considered since ARVs
may affect the sensitivity of virologic tests(BIII)
 Most HIV-exposed but uninfected children will
serorevert by age 15-18 months
 For children 18 to 24 months of age who test
Ab positive (eg, possible late seroreverters with
residual maternal Abs), a NAT should be used
for definitive exclusion or confirmation of HIV
infection(AII)
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Diagnostic Testing in Children with Perinatal
HIV Exposure >24 months of Age or in
Children with Non-Perinatal HIV Exposure
 HIV diagnosis in children >24 months of age
with perinatal HIV exposure or in children with
non-perinatal HIV exposure relies primarily on
Ab tests(AII)
 See Guidelines page C-6 for FDA-approved tests
 If acute HIV infection or end-stage AIDS is
suspected in children, a virologic test may be
necessary since Ab test results can be
negative in these situations(AII)
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Diagnostic Testing in Children with Perinatal
HIV Exposure >24 months of Age or in
Children with Non-Perinatal HIV Exposure(2)
 Sources of non-perinatal or late perinatal HIV
exposure:
 Breast-feeding
 Sexual abuse
 Parenteral exposure via contaminated blood products
(eg, some international adoptions)
 Receipt of premasticated food from an HIV-infected
caregiver
 Accidental needlesticks
 Behavioral risks (in older children)
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Diagnostic Testing in Children with
Postnatal HIV Infection(1)
 Although rare, postnatal HIV infection can occur in
HIV-exposed infants with prior negative HIV
virologic tests when there are additional HIV
transmission risks (eg, breastfeeding or receipt of
premasticated food from HIV-infected caregiver)
 Appropriate diagnostic testing will depend on the
age of the child and type of exposure (perinatal vs.
non-perinatal)
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Diagnostic Testing in Children with
Postnatal HIV Infection(2)
 Recommended HIV testing for infants who are
breast-fed by an HIV-infected woman:
 Immediate virologic testing
 Discontinue breast-feeding
 Follow-up virologic testing at 4-6 weeks, 3
months, and 6 months after breast-feeding
cessation if initial results are negative
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Diagnosis of Nonsubtype B and
Group O Infection
 HIV-1 Group M subtype B is the most prevalent
viral subtype in the United States
 HIV DNA PCR
 Less sensitive in nonsubtype B
 False-negatives reported
 HIV RNA PCR assays
 Newer real-time RNA assays more sensitive for
nonsubtype B and Group O HIV detection
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Diagnosis of Nonsubtype B and
Group O Infection (2)
 If nonsubtype B exposure is suspected in
infants (eg, parent from Africa or Asia) with
negative HIV DNA PCR, repeat test with one
of the newer real-time RNA assays
 Consult with an expert and monitor closely
 Conduct Ab testing at 18 months of age
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Diagnosis of HIV-2 Infections
 HIV-2 should be suspected in pregnant women
who are from (or have partners from) endemic
countries with:
 HIV-1 Ab-positive results on EIA screen
 Repeatedly indeterminate results on HIV-1 Western
blot, and
 HIV-1 RNA at or below the limit of detection
 Use Ab test that detects HIV-2
 Most tests detect both HIV-1 and HIV-2 but do not
distinguish the two types; can use MultiSpot or (if
HIV-2 suspected) HIV-2-specific test
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Diagnosis of HIV-2 Infections (2)
 Infants born to HIV-2-infected mothers should
be tested with HIV-2-specific virologic assays
(HIV-2 DNA PCR) at time points similar to those
used for HIV-1 testing
 HIV-2 virologic assays are not commercially
available, but the National Perinatal HIV Hotline
(1-888-448-8765) can provide a list of sites
performing this testing
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Diagnosis of HIV-2 Infections (3)
 Suspected cases should be reported to the
state or local health department in order to
arrange confirmatory testing via the CDC
 Consult with a pediatric HIV infection expert
when caring for an infant with suspected or
known HIV-2 exposure
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Clinical and Laboratory Monitoring
Virologic and Immunologic Parameters
in Pediatric HIV Infection
 CD4 counts and % values are much higher in healthy
infants and young children than in healthy adults; they
slowly decline to adult levels by age 5 years
 Absolute CD4 count is recommended for monitoring
immune status in children of all ages, with CD4% as
an alternative(AII)
 HPPMCS study: CD4% provided little or no added
prognostic value compared with CD4 count regarding
short-term disease progression in children
 Current pediatric HIV classification and thresholds for
treatment are based on absolute CD4 count
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Virologic and Immunologic Parameters
in Pediatric HIV Infection (2)
 HIV RNA (viral load or VL) is generally low at birth
(<10,000 copies/mL)
 In untreated children, HIV RNA increases to high
values (eg, >100,000 copies/mL) by 2 months of
age and then decreases slowly; high viral load
persists for prolonged periods
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Virologic and Immunologic Parameters
in Pediatric HIV Infection (2)
 Viral suppression: plasma VL below the detection
limit of the assay used (generally <20-75 copies/mL)
 Confirm HIV RNA or CD4 count/% with a second test
before making decisions about initiating or changing
therapy based on HIV RNA or CD4 count/%
 Changes in HIV RNA copies/mL of less than 5-fold
(0.7 log10) in infants <2 years of age or 3-fold (0.5
log10) in children aged ≥2 years are usually not
biologically or clinically significant
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Virologic and Immunologic Parameters
in Pediatric HIV Infection (3)
 Consider the age of child when interpreting the risk
of disease progression based on CD4 count/% and
plasma HIV RNA level
 For any CD4 count/%, younger children (especially
<12 months) have higher risk of disease progression
 Although data indicate high VL is associated with
disease progression, predictive value of HIV RNA for
an individual child is moderate
 The use of CD4 count or CD4% and HIV RNA
together more accurately defines prognosis
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CDC HIV Infection Stage Based on AgeSpecific CD4 Count or Percentage
Age on Date of CD4 Test
CDC
Stage
< 1 year
1 to < 6 years
> 6 years
Cells/µL
%
Cells/µL
%
Cells/µL
%
Stage 1
> 1500
> 33%
> 1000
> 30%
> 500
> 26%
Stage 2
750-1499
26-33%
500-999
22-29%
200-499
14-25%
Stage 3
< 750
< 26%
< 500
< 23%
< 200
< 14%
 Stage is based primarily on the CD4 count; the CD4% is
considered only if the count is missing.
 If a Stage 3-defining opportunistic illness has been
diagnosed (see Guidelines Table 6), then the stage is 3
regardless of CD4 test results.
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Baseline Assessment: Entry into Care










CD4 count and %
HIV RNA
Resistance test (genotype)
Clinical history and physical exam
CBC w/ differential
Chemistries
Lipid panel
Urinalysis
HLA-B*5701 (if treatment with ABC is being considered)
Hepatitis B virus (HBV) screening
(if considering treatment with 3TC, TDF, or FTC)
Refer to Guidelines Table 3 for updated clinical and lab monitoring schedule.
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Monitoring of Pediatric HIV Infection
 Use primary, FDA-approved assays to monitor VL
(Refer to Guidelines Table 4)
 For children not on cART:
 Monitor CD4 count/% and HIV RNA at initial
diagnosis and at least every 3-4 months(AIII)
 More frequent monitoring should be
implemented for suspected clinical,
immunologic, or virologic deterioration or to
confirm an abnormal value(AIII)
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Monitoring of Pediatric HIV Infection (2)
 After starting or changing cART regimen:
 Evaluate for side effects and support adherence within 12 weeks(AIII)
 Lab testing at 2-4 weeks for toxicity and VL response(AIII)
 Routinely assess children every 3-4 months for therapy
adherence, effectiveness (CD4 count/%, VL), and
toxicities (history, physical, selected labs)(AII)
 CD4 count/% can be monitored less frequently (every 612 months) in children with cART adherence, CD4 well
above threshold for OI risk, sustained virologic
suppression, and stable clinical status for >2-3 years(BII)
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cART Initiation in Children
cART Initiation or Change:
Factors to Consider
 HIV disease severity and risk of progression as
determined by age, presence or history of HIVrelated illnesses, degree of CD4
immunosuppression
 Availability of appropriate and palatable drug
formulations
 Regimen potency, complexity, and potential
adverse effects
 Effect of initial regimen choice on later options
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cART Initiation or Change:
Factors to Consider (2)
 cART history
 Presence of ARV-resistant virus
 Presence of comorbidities
 Potential interactions with other medications
 Anticipated ability of the child and caregiver to
adhere to the regimen
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Goals of cART
 Prevent and reduce HIV-related mortality and morbidity
 Restore and preserve immune function
 Achieve maximal and durable viral suppression
 Prevent emergence of viral drug resistance
 Minimize drug-related toxicity
 Maintain normal physical growth and development
 Improve quality of life
 Reduce risk of sexual transmission to partners in
adolescents who are sexually active
 Reduce risk of perinatal transmission in adolescent
females who become pregnant
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Initiation of cART in ARV-Naive Children
 Treatment recommendations have been
revised to incorporate the updated CDC
Surveillance Case Definition for HIV
infection
 The Panel has stratified the urgency for
initiation of treatment based on the risk of
disease progression in children <12 months
of age or the presence of CDC Stage 3defining opportunistic illness or Stage 3
CD4 counts (see Guidelines Tables 6 & 7)
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Initiation of cART in ARV-Naive Children (2)
Infants <12 months of age:
 Youngest children are at high risk of rapid
disease progression
 Clinical and laboratory markers are poor
indicators of risk of rapid progression in
infants
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Initiation of cART in ARV-Naive Children (3)
cART should be initiated urgently in any of
the following situations:
 All HIV infected children age <12 months(AI for
infants <12 weeks, AII for infants 12 weeks to 12 months)
 A CDC Stage 3-defining opportunistic illness(AI)
(See Guidelines Table 7)
 CDC Stage 3 CD4 count(AI)
 Ages 1 to <6 years, CD4 count <500 cells/µL
 Age ≥6 years, CD4 count <200 cells/µL
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Initiation of cART in ARV-Naive Children(4)
cART should be initiated in HIV-infected
children age ≥1 year with any of the following:
 Moderate HIV-related symptoms(AII)
(See Guidelines Table 7)
 Plasma HIV RNA >100,000 copies/mL(AII)
 CDC Stage 2:
 Ages 1 to <6 years, CD4 count 500-999
cells/µL(AII)
 Age ≥6 years, with CD4 count <200-499
cells/µL(AI* if CD4 count <350 cells/µL, AII* if CD4 count 350499 cells/µL)
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Initiation of cART in ARV-Naive Children (5)
 cART should be considered for HIV-infected
children aged ≥1 year who are asymptomatic or
have mild symptoms (see Guidelines Table 7) and have
CDC Stage 1 CD4 count:
 Ages 1 to <6 years, CD4 count ≥1,000
cells/µL(BIII)
 Age ≥6 years, CD4 count ≥500 cells/µL(BIII)
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Initiation of cART in ARV-Naive Children (6)
 CD4 counts should be confirmed by a second
test to meet treatment criteria before initiation of
cART
 To avoid overestimation of temporary blips in
viral load, HIV RNA >100,000 copies/mL should
be confirmed before initiating cART
 Temporary blips can occur during
intercurrent illnesses
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Initiation of cART in ARV-Naive Children (7)
 Urgent treatment is recommended in children
with the highest risk of disease progression,
morbidity, mortality
 Treatment should be initiated within 1-2
weeks, including an expedited discussion on
adherence and increased, intensive followup for support
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Initiation of cART in Children
Age
<12 Months
1 to <6 Years
Criteria
Recommendation
Regardless of clinical symptoms,
immune status or viral load
Urgent treatment (AI for <12 weeks
of age; AII for ≥12 weeks)
CDC Stage 3-defining
opportunistic illnessesb
Urgent treatment (AI*)
CDC Stage 3 immunodeficiency:d
CD4 count <500 cells/mm3
Urgent treatment (AI*)
Moderate HIV-related symptomsb
Treat (AII)
HIV RNA >100,000 copies/mLc
Treat (AII)
CD4 countd 500-999 cells/mm3
Treat (AII)
Asymptomatic or mild symptomsb
and CD4 countd ≥1,000 cells/mm3
Consider treatment (BIII)
a Children in whom cART is deferred need close follow-up. Factors to consider in deciding when to initiate therapy in children in whom
treatment was deferred include:
• CD4 cell count or percentage values approaching the age-related threshold for treatment;
• Development of clinical symptoms; and
• The ability of caregiver and child to adhere to the prescribed regimen.
b Table 7
c To avoid overinterpretation of temporary blips in viral load (which can occur during intercurrent illnesses, for example), plasma
HIV RNA level >100,000 copies/mL should be confirmed by a second level before initiating cART.
d Laboratory data should be confirmed with a second test to meet the treatment criteria before initiation of cART.
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Initiation of cART in Children (2)
Age
≥6 Years
Criteria
Recommendation
CDC Stage 3-defining opportunistic
illnessesb
Urgent treatment (AI*)
CDC Stage 3 immunodeficiency:d CD4
count <200 cells/mm3
Urgent treatment (AI*)
Moderate HIV-related symptomsb
Treat (AII)
HIV RNA >100,000 copies/mLc
Treat (AII)
CD4 countd 200-499 cells/mm3
Treat (AI* for CD4 count <350
cells/mm3 and AII* for CD4 count
350-499 cells/mm3)
Asymptomatic or mild symptomsb and
CD4 countd ≥500 cells/mm3
Consider treatment (BIII)
a Children in whom cART is deferred need close follow-up. Factors to consider in deciding when to initiate therapy in children in whom
treatment was deferred include:
• CD4 cell count or percentage values approaching the age-related threshold for treatment;
• Development of clinical symptoms; and
• The ability of caregiver and child to adhere to the prescribed regimen.
b Table 7
c To avoid overinterpretation of temporary blips in viral load (which can occur during intercurrent illnesses, for example), plasma
HIV RNA level >100,000 copies/mL should be confirmed by a second level before initiating cART.
d Laboratory data should be confirmed with a second test to meet the treatment criteria before initiation of cART.
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Initiation of cART in ARV-Naive Children
 Therapy adherence issues should be assessed and
discussed with the HIV-infected child’s caregivers
before initiation of cART(AIII)
 Medication adherence is the core requirement for
successful virologic control, but enforcing consistent
adherence in childhood is often challenging
 In nonurgent situations, parents/caregivers or
providers may elect to defer therapy based on
clinical and/or psychosocial factors on a case-bycase basis
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Indicators of Need to Start cART in ARVNaive Children
 Children in whom cART is deferred need close
follow-up; factors to consider in deciding when to
initiate cART in children in whom cART was
deferred include:
• Increasing VL (such as VL approaching 100,000
copies/mL)
• CD4 count or % approaching age-related threshold
for cART
• Development of clinical symptoms
• Ability of caregiver and child to adhere to regimen
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Pediatric cART Regimens
Criteria Used for Recommendations about
Specific ARV Drugs and Drug Regimens
 Data demonstrating durable viral suppression,
immunologic and clinical improvement
 Pediatric experience
 Incidence and types of ARV toxicity
 Availability/palatability of pediatric formulations
 Dosing frequency, food and fluid requirements
 Potential for drug interactions
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Recommendations for Initial Therapy in
ARV-Naive Children
 Preferred
 Clinical trial data in children, more often data in adults, shows
optimal and durable efficacy with acceptable toxicity and ease of
use
 Safety and efficacy are suggested using surrogate markers in
pediatric studies
 Alternative
 Clinical trial data show efficacy, but there are disadvantages
compared with preferred regimen (eg, more limited data in children,
efficacy or durability less well defined, toxicity concerns)
 Use in Special Circumstances
 Regimens to be used only when preferred or alternative drugs or
drug regimens cannot be used
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Initial cART for ARV-Naive Children
Preferred Regimens
Children aged ≥14 days to <3 yearsa
Two NRTIs plus LPV/r
Children aged ≥3 years to <6 years
Two NRTIs plus EFVb
Two NRTIs plus LPV/r
Children aged ≥6 years
Children aged ≥6 years
Two NRTIs plus EFVb
Two NRTIs plus LPV/r
a LPV/r should not be administered to neonates before a postmenstrual age (first day of the mother’s last
menstrual period to birth plus the time elapsed after birth) of 42 weeks and postnatal age ≥14 days.
b EFV is licensed for use in children aged ≥3 months who weigh ≥3.5 kg but is not recommended by the Panel as
initial therapy in children aged ≥3 months to 3 years. Unless adequate contraception can be ensured, EFV-based
therapy is not recommended for adolescent females who are sexually active and may become pregnant.
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Initial cART for ARV-Naive Children
Alternative Regimens
Children aged >14 days
Two NRTIs plus NVPc
Children aged ≥3 months to <6 years and weighing ≥10 kg
Two NRTIs plus ATV plus low-dose RTV
Children aged ≥2 years
Two NRTIs plus RALd
Children aged ≥3 years to <12 years
Two NRTIs plus twice-daily DRV plus low-dose RTV
Children aged ≥12 years
Two NRTIs plus once-daily DRV plus low-dose RTVe
Two NRTIs plus DTG
Regimens for Use in Special Circumstances
Children aged ≥4 weeks and <2 years and weighing ≥3 kg
Two NRTIs plus RALd
Children aged ≥6 months
Two NRTIs plus FPVf plus low-dose RTV
Children aged ≥2 years
Two NRTIs plus NFV
Children ≥12 years
Two NRTIs plus DTG
Treatment-naive adolescents aged ≥13 years and weighing >39 kg
Two NRTIs plus ATV unboosted
c NVP should not be used in postpubertal girls with CD4 cell count >250/mm3, unless the benefit clearly outweighs
the risk. NVP is FDA-approved for treatment of infants aged ≥15 days.
d RAL pills or chewable tablets can be used in children aged ≥2 years as an alternate INSTI. Use of granules or
chewable tablets in infants and children aged 4 weeks to 2 years can be considered in special circumstances.
e DRV once daily should not be used if any one of the following resistance-associated substitutions are present
(V11I, V32I, L33F, I47V, I50V, I54L, I54M,T74P, L76V, I84V, and L89V).
f FPV with low-dose RTV should only be administered to infants born at ≥38 weeks’ gestation who have attained a
postnatal age of 28 days and to infants born before 38 weeks’ gestation who have reached a postmenstrual age
of 42 weeks.
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Initial cART for ARV-Naive Children
Preferred 2-NRTI Backbone Options for Use in Combination with Additional Drugs
Children, birth to 3 months
ZDV plus (3TC or FTC)
Children aged ≥3 months and ≤12 years
ABC plus (3TC or FTC)
ZDV plus (3TC or FTC)
Adolescents aged ≥13 years at Tanner Stage ≤3
ABC plus (3TC or FTC)
Adolescents at Tanner Stage 4 or 5
ABC plus (3TC or FTC)
TDF plus (3TC or FTC)
Alternative 2-NRTI Backbone Options for Use in Combination with Additional Drugs
Children aged ≥2 weeks
ddI plus (3TC or FTC
ZDV plus ddI
Children ≥3 months
ZDV plus ABC
Children and adolescents at Tanner Stage 3
TDF plus (3TC or FTC)
Adolescents ≥13 years
ZDV plus (3TC or FTC)
2-NRTI Regimens for Use in Special Circumstances in Combination with Additional Drugs
•
•
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d4T plus (3TC or FTC)
TDF plus (3TC or FTC) (prepubertal children aged ≥2 years and adolescents, Tanner Stage
1 or 2)
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Factors to Consider When Selecting an
Initial Regimen
 Selection of regimen should be individualized;
consider(AIII):
 Characteristics of the regimen
 Including barriers to adherence (eg, palatability)
 Potential limitations in subsequent treatment options should
resistance develop
 Patient characteristics
 Results of resistance testing
 Note that an “alternative” regimen may be
preferred for some patients
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NNRTI-Based Regimens
Advantages
Disadvantages
 Long half-lives
 Lower risk of
dyslipidemia and fat
maldistribution than
seen with PIs
 PI-sparing
 Lower pill burden
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 Single mutation can confer
high-level resistance;
cross-resistance between
EFV and NVP
 Risk of serious or lifethreatening rash (eg, SJS)
and hepatitis (rare)
 Potential for multiple drug
interactions
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PI-Based Regimens
Advantages
Disadvantages
 Metabolic complications (eg,
dyslipidemia, insulin resistance,
fat maldistribution)
 NNRTI-sparing
 Efficacy well
documented
 Resistance requires
multiple mutations
 Targets HIV at 2 steps
of viral replication when
combined with dualNRTI backbone

Some powder and
liquid formulations
available
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 Potential for multiple drug
interactions (particularly with
low-dose ritonavir boosting
needed for most PIs)
 Higher pill burden
 Poor palatability of liquid
formulations
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INSTI-Based Regimens
Advantages
 Susceptibility of HIV
to a new class of
ARVs
 Some (RAL) available
in chewable tablet or
powder formulation
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Disadvantages
 Limited data on
pediatric dosing and
safety
 Potential drug-drug
interactions
 Potential for rare
systemic allergic
reaction or hepatitis
(RAL)
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Guidelines Appendix A: Pediatric ARV
Drug Information
 Provides concise drug tables with detailed dosing,
selected adverse effects, special instructions, and
metabolism
 Also provides information about drug interactions, major
toxicities, resistance, and pediatric use, including PK
 Identifies situations wherein recommended pediatric use
of an ARV differs from FDA approval; eg, although FDA
approved EFV for ages ≥3 months, Guidelines Panel does
not recommend its use for children <3 years
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Initial Therapy for ARV-Naive Children
 For infants aged <42 weeks postmenstrual or
<14 days postnatal, current data are insufficient
to provide recommended dosing for a complete,
effective cART regimen
 Neonatal care providers should consult with
pediatric HIV specialist before initiating cART
on a preterm neonate or a full-term neonate <2
weeks of age or contact the National Perinatal
HIV Hotline
 Review Pediatric Opportunistic Infections
Guidelines for preferred cART regimens to use
with HBV, HCV, or TB coinfection
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Initial Therapy for cART-Naive Children:
Not Recommended
Not Recommended due to concerns about inferior virologic response,
safety, or pharmacologic antagonism. Drugs/regimens not recommended
due to insufficient data are denoted by *.
• Unboosted ATV for age <13 years • Unboosted FPV (reduced
and/or <39 kg (reduced exposure)
exposure, medication burden)
• DRV/r once daily for age ≥3 to 12
years*
• IDV (renal toxicities)
• Unboosted DRV (not studied)
• LPV/r once daily (reduced
exposure)
• Dual- (full-dose) PI regimens*
• MVC-based regimens*
• EFV for children aged <3 years
(appropriate dosage not
determined)
• NFV for age <2 years (dosage not
determined)
• ENF* containing regimens (also
injection)
• ETR–based regimens
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• NRTI-only regimens (inferior
virologic efficacy)
• EVG-based regimens
• DTG age <12 yrs or weight <40 kg*
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Initial Therapy for cART-Naive Children:
Not Recommended (2)
Not Recommended due to concerns about inferior virologic response,
safety, or pharmacologic antagonism. Drugs/regimens not
recommended due to insufficient data are denoted by *.
• RPV-based regimens*
• Full-dose RTV or RTV as sole
PI (GI intolerance, metabolic
toxicity)
• SQV (limited dosing and outcome
data)
• ABC + ddI as dual NRTI*
• ABC + TDF as dual NRTI*
• TDF for children aged <2 years • d4T + ddI as dual NRTI (significant
(potential bone toxicity, dose
toxicities)
not determined)
• TDF + ddI as dual NRTI (increased
• TPV (increased RTV for
concentrations, high rate VF)
boosting, intracranial
• 3-class regimens*
hemorrhage)
• 3 NRTIs + NNRTI*
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ARV Regimens or Components
Never Recommended for Children
Regimens or Regimen Components That Should NEVER Be
Offered due to high rates of resistance, virologic failure,
serious toxicity, and other reasons. See Guidelines Table 11 for
specific rationale.
•
•
•
•
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Monotherapy (1 ARV drug)
2 NRTIs alone
Certain dual-NRTI combinations as
part of a regimen:
• 3TC + FTC
• ZDV + d4T
Certain NRTI-only regimens:
• TDF + ddI + (3TC or FTC)
• TDF + ABC + (3TC or FTC)
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•
•
•
•
•
Unboosted DRV, SQV, or TPV
ATV + IDV
Dual-NNRTI combinations
EFV in first trimester of pregnancy or
for sexually active girls of childbearing
potential when reliable contraception
cannot be ensured
Initiating NVP in adolescent girls with
CD4 count >250 cells/µL or adolescent
boys with CD4 count >400 cells/µL
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Considerations for Adolescents
Considerations for Adolescents
 cART regimens MUST be tailored to meet the
needs of the adolescent(AIII)
 Dosing for adolescents may be complex and is
dependent on multiple factors including body
mass and composition, and pubertal
development(AII)
 Effective and appropriate precautions need to
be taken to reduce the risk of unintended
pregnancy and to prevent HIV transmission to
sex partners(AI)
 Awareness of potential interactions between
ARVs and hormonal contraceptives that could
lower contraceptive effectiveness(AII*)
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Considerations for Adolescents (2)
 Regimens that do not include EFV should be
strongly considered in adolescent females trying to
conceive and in those who are not using effective
and consistent contraception, assuming alternative
regimens are acceptable(BIII)
 Potential for teratogenicity with 1st-trimester EFV
exposure
 Perform pregnancy testing and conduct counseling
about potential fetal risk and the desirability of avoiding
pregnancy while receiving EFV(AIII)
 Women with HIV can use all available contraceptive
methods (including the IUD)
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Considerations for Adolescents (3)
 Prepare adolescents for the transition to adult care
settings(AIII), taking into account features of an adult
care setting that the adolescent/young adult
identifies as most important in going for care; social
determinants to consider include:






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Developmental status/peer pressure/disclosure issues
Behavioral/mental health/substance use issues
Housing issues
Family or other support(s)
Employment issues
Recent discharge from foster care or incarceration
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cART Adherence Issues
Adherence
 Prior to initiating or changing cART, address
strategies to maximize adherence(AIII)
 Stress adherence to therapy at each visit; continue
to explore strategies to maintain or improve
adherence(AIII)
 In addition to viral load monitoring, use at least one
other method of measuring cART adherence(AII)
 A once-daily cART regimen should be used, if
feasible(AI*)
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Adherence
 Providers should maintain a nonjudgmental
attitude, establish trust with patients/caregivers,
and identify mutually accepted goals to improve
and support adherence(AII*)
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Adherence Issues Specific to Children
 Availability of drugs in palatable, liquid, powder or
mixable formulations; pill swallowing difficulties
 Dependence on caregivers for administration
 Families’reluctance to disclose HIV diagnosis
may limit medication administration
 Reliance on older child to self-administer without
appropriate caregiver monitoring
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Adherence Issues Specific to Children (2)
 Timing issues (eg, during school hours)
 Barriers faced by adult caregivers (eg,
forgetting doses, changes in routine, being
too busy, and child refusal)
 Social issues within the family, such as illicit
substance use, caregiver illness, unstable
housing, and involvement with the criminal
justice system
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Adherence Issues Specific to Adolescents
 Denial and fear of HIV
infection
 Misinformation
 Pill burden
 Lack of belief in the
effectiveness of ARVs
 Distrust of the medical
establishment
 Low self-esteem
 Disclosure issues
 Alcohol and substance
use
 Lack of familial and
social support
 Unstructured and chaotic
lifestyle
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 Depression
 Advanced HIV disease,
illness
 Regimen fatigue
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Supporting Adherence with Adolescents
 Assess readiness to adhere and
understanding of adherence
 Involve family, peers, partners when possible
 Use reminder systems (eg, SMS text message
reminders)
 Use pillboxes and medication organizers
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Assessing and Monitoring Adherence
 Difficult to assess accurately
 Adherence can change over time; regular follow-up
is essential (particularly when starting or restarting
cART)
 Use at least one method in addition to VL:
 Quantitative self-report (most recent past 3-day or 7-day
report of adherence or nonadherence)
 Targeted questions
 Pharmacy refill checks, pill counts
 Electronic monitoring devices: Medication Event
Monitoring Systems (MEMS); SMS text messaging
 Home visits; DOT or m-DOT
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Assessing and Monitoring Adherence:
Initial Adherence Intervention Strategies
 Establish trust; identify mutually acceptable goals for care
 Obtain explicit agreement on a treatment plan (including
need for cART and need for adherence)
 Identify and treat mental health issues
 Identify a support team (family, friends, health care team)
 Educate patient and family (adherence, partial adherence,
resistance)
 Specify the adherence target: ≥95% of prescribed doses
 Establish readiness (practice sessions or other means)
 In selected circumstances, consider brief hospitalization (to
initiate cART, evaluate tolerability, and provide education)
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Strategies to Improve Adherence:
Medication Strategies to Support Adherence
 Choose the simplest regimen possible, reducing
dosing frequency and number of pills
 Consider patient/family’s daily and weekly routines
 Consider palatability (pharmacist may be able to add
flavor/syrup)
 Choose drugs with fewest side effects; provide
anticipatory guidance on management
 Simplify food requirements for dosing
 Avoid adverse drug-drug interactions
 Assess pill-swallowing; offer training
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Strategies to Improve Adherence:
Follow-Up Strategies to Support Adherence
 Monitor adherence at each visit and in between by phone,
SMS text, or letter
 Support, encourage, and understand difficulties
 Use education aids (eg, pictures, calendars, stickers)
 Encourage use of supports such as pillboxes, alarms
 Provide support groups, counseling, mental health or drug
treatment access
 Establish pharmacist-based support (eg, education, refill
reminders, home delivery of medications)
 In selected circumstances, consider: brief hospitalization,
gastrostomy tube placement, DOT
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Management of cART Toxicity or
Intolerance
Management of cART Toxicity or Intolerance
 Adverse effects or side effects of ARVs are
generally mild to moderate
 Recognize that even mild adverse effects may
negatively impact adherence
 It is very important to assess, anticipate, and
manage common adverse effects
 For mild-to-moderate transient intolerance, treat
symptomatically
 Refer to the Guidelines toxicity tables for
information about specific adverse effects, including
prevention and management
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Management of cART Toxicity or Intolerance (2)
 If severe or life-threatening toxicity: stop ALL ARVs
immediately(AIII)
 When modifying cART due to toxicity or intolerance of a
specific ARV in a child with virologic suppression, it is
permissible to change just one drug in the regimen to
another active agent with a different toxicity/side-effect
profile(AI*)
 Once toxicity has been resolved, resume cART with
substitute ARV(s) for the offending agent(s)(AII*)
 Document toxicity and the responsible ARV(s); advise
caregiver and patient of the adverse effect(AIII)
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Management of cART Toxicity or Intolerance (3)
 Dosage reduction is NOT recommended for ARV
toxicity management except for the few ARVs for
which therapeutic range plasma concentrations
detected by therapeutic drug monitoring correlates
with toxicity(AII*)
 If necessary, change to another ARV (within the same
drug class) to which the patient’s virus is sensitive
 If necessary, change to another drug class (different
from the previous toxic/intolerant ARV class) to which
the patient’s virus is sensitive
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Modifying cART in Children to Promote
Sustained Viral Suppression
Recommendations
 For children with sustained virologic suppression on a
particular cART regimen (eg, 6-12 months), changing to a
new cART regimen with improved pill burden or tolerance
should be considered to promote adherence and improve
safety(BII)
 Review of past ART failures and drug-resistance testing is
essential to avoid selection of a suboptimal new cART
regimen
 To promote ease of cART administration and adherence,
possible changes include substitution of:
 Pill formulation for liquid
 Once-daily regimen for twice-daily regimen
 1 pill for 2 or more pills
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Possible Regimen Simplification Changes for
Virologically Suppressed Children
ARV Drug(s)
Current
Age
Body Size
Potential ARV Regimen Change
ZDV, ddI, or d4T* ≥1 year
N/A
ABC (once-daily dosing)
ABC twice daily
≥1 year
Any
ABC once-daily dosing
LPV/r twice daily
≥1 year
≥3 kg
RAL (better palatability) or ATV/r (oncedaily dosing)
LPV/r twice daily
≥3 years
N/A
EFV (once-daily dosing), DRV/r; better
palatability and lipid profile
LPV/r twice daily
≥12 years
≥40 kg
DRV/r (once-daily dosing)
ZDV or ddI
≥13 years
Tanner
Stage IV-V
TDF or ABC (once-daily dosing)
Any multi-pill or
twice-daily
regimen
≥13 years
Tanner
Stage IV-V
Coformulated TDF/FTC/EFV,
TDF/FTC/RPV, TDF/FTC/EVG/COBI, or
ABC/3TC/DTG (all 1 pill once daily)
* d4T may be replaced with a safer drug even before sustained viral suppression
because of long-term safety concerns
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Treatment Failure
Treatment Failure
 Assess and address causes of virologic treatment
failure, including poor adherence, drug resistance,
poor drug absorption, inadequate dosing, and drugdrug interactions(AII)
 Following treatment failure, the goal is to achieve and
maintain virologic suppression(AI*)
 ARV regimens should be chosen based on treatment
history and the results of both current and past drugresistance testing(AI*)
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Treatment Failure (2)
 Perform ARV drug-resistance testing when virologic
failure occurs, while the patient is still taking the
failing regimen and before changing to a new
regimen(AI*)
 The new regimen should include at least 2, but
preferably 3, fully active ARV drugs with assessment
of anticipated ARV activity based on resistance test
results and past treatment history(AII*)
 Evaluation and management of treatment failure
should be conducted in collaboration with a pediatric
HIV specialist(AI*)
 When complete virologic suppression is
unobtainable, the goals are to preserve/restore
immunologic function, prevent disease progression,
and prevent more drug resistance(AII)
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Virologic Failure
 Incomplete initial virologic response to cART or viral
rebound after achieving virologic suppression
 HIV RNA >200 copies/mL after 6 months of cART, or
 Repeated HIV RNA above the level of detection after 12
months of cART, using most sensitive assay
 Virologic suppression is defined as having plasma
HIV RNA below the limit of quantification by the most
sensitive assay (ie, <20-75 copies/mL)
 Use of assays unable to quantify levels below 200 or 400
copies/mL is not recommended
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Virologic Failure (2)
 Infants with high viral loads at initiation of therapy
occasionally take >6 months to reach undetectable
levels
 Isolated “blips” (above the level of quantification but
<500 copies/mL) followed by a return to viral
suppression are common and generally do not indicate
failure
 Repeated plasma HIV RNA detection above the level
of detectable quantification (especially if >500
copies/mL) after achieving viral suppression usually
indicates virologic failure
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Immunologic Failure
 Defined as an incomplete immunologic response to
cART or immunologic decline while on cART such
that there is a failure to achieve or maintain a CD4%
or count that is above the age-specific range for
severe immunodeficiency
 Consider normal age-related changes in CD4 cell
count
 CD4 count values decline with age whereas CD4%
varies less with age
 Absolute CD4 counts approach those of adults by age 5
 Absolute CD4 count may be used at ≥5 years of age
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Clinical Failure
 The occurrence of a new OI or other clinical
evidence of HIV disease progression during cART
 The most concerning type of treatment failure and
requires immediate evaluation
 Clinical events in the first several months after cART
initiation often do not represent clinical failure; may
reflect persistent immune dysfunction or IRIS
 Must be viewed alongside virologic and
immunologic response to cART; if virologic and
immunologic measures are stable, events may
not have resulted from treatment failure
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Differences in Virologic, Immunologic, and
Clinical Responses to Treatment
 Failure of viral suppression generally leads to
immunologic and/or clinical failure
 However, some children can present with failure in
one domain with a good response in the other two
 It is important to consider and evaluate alternative
causes for discordance between virologic,
immunologic, and clinical responses before
concluding that treatment failure has occurred
 Host genetic or virologic characteristics, lab error, adverse
drug effects, medical conditions (eg, malnutrition,
malignancy, pulmonary tuberculosis), IRIS, malnutrition,
loss of CD4 reserve, etc
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Assessment and Management of Treatment
Failure: Adherence to Therapy
Assessment
•
•
•
•
Intervention
Interview child and caretaker
 24-hour or 7-day recall
 Ask about the who gives, when
takes, what takes, where
kept/given, and how feels of
med administration
 Explore barriers and challenges
Review pharmacy records
Observe medication administration
Conduct psychosocial assessment
(caregiver, substance use, mental
health, health beliefs, disclosure, and
peer pressure issues)
•
•
•
•
•
•
•
•
•
•
•
Identify or reengage adherence support
persons/supervision
Establish fixed times and routines
Review generic/trade names
Explore possibilities for DOT
Simplify regimen, if possible
Substitute new ARV if single ARV not
tolerated
Consider gastric tube, DOT
Use tools (eg, pillboxes, reminders)
Address behavior, mental illness,
competing needs
Initiate disclosure discussions
Consider child protective
services/alternative care settings
See Guidelines Table 14 about the assessment and management of
treatment failure.
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Assessment and Management of Virologic
Failure: PK and Dosing Issues
Assessment
• Recalculate dosages using weight or
BSA
• Identify all concomitant medications,
including prescription, OTC,
recreational substances; assess for
drug-drug interactions
Intervention
• Adjust drug dosages
• Discontinue or substitute
competing medications
• Reinforce applicable food
restrictions
• Consider checking drug levels for
specific ARVs
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Assessment and Management of Virologic
Failure: ARV Drug Resistance
Assessment
Intervention
• Perform resistance testing, as
appropriate
• If no resistance detected, focus on
improving adherence
• If resistance to current regimen
detected, optimize adherence and
evaluate potential for a new regimen
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Options for Regimens in Patients with
Treatment Failure and Viral Resistance
• Consult with an expert in pediatric HIV infection;
• may consider:
Prior Regimen
Recommended Change
(in order of relative preference)a
2 NRTIs + NNRTI
• 2 NRTIs + PI
• 2 NRTIs + INSTI
2 NRTIs + PI
•
•
•
•
a
2 NRTIs + NNRTI
2 NRTIs + different RTV-boosted PI
2 NRTIs + INSTI
NRTI(s) + INSTI + (NNRTI or different RTVboosted PI)
ARV regimens should be chosen based on treatment history and drug-resistance
testing. Note that, with NNRTI- and INSTI-based regimens, resistance can develop
rapidly if the NRTIs do not have full activity. See Guidelines.
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Treatment Failure and Viral Resistance Options
Prior Regimen
3 NRTIs
Recommended Change
(in order of relative preference) a
• 2 NRTIs + (NNRTI or PI)
• 2 NRTIs + INSTI
• INSTI + 2 other active drugs (chosen from NNRTI,
PI, NRTI groups)
Failed regimen(s) • 2 NRTIs + INSTI (+ RTV-boosted PI if needed)
that included:
• NRTI(s) + RTV-boosted PI + INSTI (consider adding
NRTI(s),
T20 and/or MCVb if needed)
NNRTI(s), and
• NRTI(s) + RTV-boosted DRV, LPV, or SQV + ETR
PI(s)
(consider adding INSTI, T-20 and/or MCVb if needed)
• >1 NRTI + 2 RTV-boosted PIs (LPV/r + SQV, LPV/r +
ATV) (consider adding INSTI or T-20 if needed)
a
ARV regimens should be chosen based on treatment history and drug-resistance
testing. Note that, with NNRTI- and INSTI-based regimens, resistance can develop
rapidly if the NRTIs do not have full activity. See Guidelines.
b No current FDA-approved pediatric indication for maraviroc.
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Discontinuation or Interruption of
cART
cART Interruptions
 Structured interruptions of cART are NOT
recommended except within the context of a clinical
trial(AIII)
 Short-term interruptions may occur as a result of:
acute illness, drug-related toxicity, lack of medication,
planned surgery, sedation or procedures that limit
oral intake, and request of patient/caregiver; in these
cases, cART should be restarted as soon as possible
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Therapeutic Drug Monitoring
Role of Therapeutic ARV Drug Monitoring
 Evaluation of plasma concentrations of ARV drugs are
not required of most HIV-infected children, but may be
considered for children on cART under the following
circumstances(BII):
 Use of ARV drugs with limited PK data and
therapeutic experience in children
 Unexpected suboptimal treatment response
 Significant drug-drug or food-drug interactions
 Suspected suboptimal drug absorption

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Role of Therapeutic ARV Drug Monitoring (2)
 Check for G516T polymorphism of cytochrome
P450 (CYP450) 2B6, in combination with testing
of plasma EFV levels, is recommended in
children <3 years receiving EFV(AII), may be
considered in older children and adolescents
 This polymorphism is associated with EFV
concentrations
 Pretreatment evaluation of CYP450 genotype in
children <3 years of age prior to initiating EFV for
dosing purposes (see Guidelines)
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ARV Drug Resistance Testing
Resistance Testing Recommendations
 ARV drug-resistance testing is recommended at the
time of HIV diagnosis, before initiation of cART, in all
ARV-naive patients(AII)
 Genotypic resistance testing is preferred for initial
resistance testing(AIII)
 ARV drug-resistance testing is recommended before
changing therapy because of treatment failure(AI*)
 Testing should be done while patient is still on
failing regimen or within 4 weeks of
discontinuation(AII*)
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Resistance Testing Recommendations (2)
 Use phenotype (usually in addition to genotype) for known or
suspected complex drug resistance(BIII)
 Absence of detectable resistance to a drug does not ensure
its efficacy (mutations may not be detected once drug is
stopped); ARV history and previous resistance test results
must be considered when choosing new ARV drugs after
virologic failure(AII)
 Use viral coreceptor (tropism) assays when considering use
of a CCR5 antagonist(AI*)
 Consider tropism assays for patients with virologic failure on
therapy containing a CCR5 antagonist(AI*)
 Consultation with pediatric HIV specialist is recommended for
interpreting resistance test results(AI*)
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Resistance Testing Recommendations (3)
Resistance Test
Standard Genotype
(protease, reverse
transciptase)
Initial Treatment
Virologic Failure
YES
YES
Integrase
phenotype/genotype
If concern for
acquisition of
resistant virus
If failure on integrase
inhibitor
Coreceptor tropism
assay
If considering
CCR5 antagonist in
initial regimen
If considering CCR5
antagonist for subsequent
regimen
Phenotype (protease,
reverse transciptase)
If genotypic
evidence of
multidrug-resistant
virus
May assist in determining
most active cART regimen
when multidrug resistance
exists (use in conjunction
with genotype results and
cART history)
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Conclusion
 Clinical care and treatment is complex and
evolves rapidly – check current Guidelines
 Because of the complexity of care issues, health
care providers should consult with a pediatric
HIV specialist when caring for a child with HIV
 Published text posted on www.aidsinfo.nih.gov
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About This Slide Set
 This presentation was prepared by John Nelson,
PhD, CPNP; Deborah Storm, MSN, PhD; and
Susa Coffey, MD, for the AETC NRC in March
2015
 See www.aidsetc.org for the most current version
of this presentation
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