Care and treatment support of HIV-Infected Children/Adolescents Dr. Maes Philip Bart Peeters Myriam Willems Centrum Begeleiding Seropositieve Kinderen – Aidsreferentiecentrum ZNA/UZA/ITG
Cursus hiv en aids, de multi-disciplinaire aanpak Les 6 8 april 2008 www.itg.be | rubriek Onderwijs & Training
Topic outline
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HIV overview HIV in children HIV in adolescents MTCT prevention
08 APR 2008
HIV Overview
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08 APR 2008
Adults and children estimated to be living with HIV, 2007 Western & Eastern Europe Central Europe & Central Asia
760 000
North America
1.3 million
[480 000 – 1.9 million]
Caribbean
230 000
1.6 million
[600 000 – 1.1 million] [1.2 – 2.1 million] East Asia
Middle East & North Africa
[210 000 – 270 000]
380 000
[270 000 – 500 000]
Sub-Saharan Africa
Latin America
1.6 million
[1.4 – 1.9 million]
22.5 million
[20.9 – 24.3 million]
800 000
[620 000 – 960 000]
South & South-East Asia
4.0 million
[3.3Oceania – 5.1 million]
75 000
[53 000 – 120 000]
Total: 33.2 (30.6 – 36.1) million
Children (<15 years) estimated to be living with HIV, 2007 Western & Eastern Europe Central Europe & Central Asia
3000
North America
11 000
[4500 – 20 000]
Caribbean
10 000
[2400 – 12 000]
12 000
[8700 – 15 000]
Middle East & North Africa
[8300 – 16 000]
28 000
[19 000 – 32 000]
Sub-Saharan Africa Latin America
39 000
[33 000 – 51 000]
2.2 million
[2.0 – 2.3 million]
East Asia
9100
[2400 – 12 000]
South & South-East Asia
120 000
[71 000 – 130 000] Oceania
1400
[1100 – 2800]
Total: 2.5 (2.2 – 2.6) million
Estimated number of children (<15 years) newly infected with HIV, 2007 Western & Eastern Europe Central Europe & Central Asia
<1000
North America
1600
[<1000]
Caribbean
2000
[630 – 3100]
3500
[2200 – 6400]
Middle East & North Africa
[1800 – 3400]
5500
[3800 – 8200]
Sub-Saharan Africa Latin America
6700
[5500 – 12 000]
370 000
[320 000 – 470 000]
East Asia
2100
[<1000 – 2100]
South & South-East Asia
24 000
[14Oceania 000 – 31 000]
<1000
[<1000 – 1400]
Total: 420 000 (350 000 – 540 000)
Over 6800 new HIV infections a day in 2007
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More than 96% are in low and middle income countries
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About 1200 are in children under 15 years of age
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About 5800 are in adults aged 15 years and older of whom: — almost 50% are among women — about 40% are among young people (15-24)
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08 APR 2008
HIV in children
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HIV in children
HAART? When to start HAART? What HAART to start with? When to change HAART?
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HAART?
Highly Active Anti Retroviral Therapy Þ Dramatic fall in child and adult mortality from HIV infection in Europe Þ Very expensive Þ major impact on the family Þ Wide variation in prescribing practice across Europe: from 50% to 97% in different countries Þ Problems of compliance/adherence 11
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Guidelines for HAART in HIV+ Children U.S.A.: 1993: Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children: convened by the NPHRC, HRSA & NIH 1998: CDC: MMWR: April 17, 1998/Vol.47/No. RR-4 2007: Most recent update Nov. 2007. Europe: 09/99: Current evidence for the use of Pediatric Antiretroviral Therapy - A PENTA Analysis Belgium: National Pediatric Working group every 3 months with review of the guidelines once a year
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When to start HAART? - No randomised trial evidence is available - So decisions to start are based on: clinical disease stage? viral load ? CD4% ? cfr.: CDC 1994 Revised classification system for HIV infection in children less than 13 years of age. - AIDS stadium or not ? - Age ? 13
08 APR 2008
Table 1: 1994 Revised HIV pediatric classification system: Immune categories based on Age-specific CD4+ T-cells count and %
Immune category Category 1No suppression
<12 months No./µL %
1-5 years No./µL %
≥ 1500
≥ 1000
≥ 25%
≥ 25%
6-12 years No./µL % ≥ 500
≥ 25%
Category 2750-1499 15%-24% 500-999 15%-24% 200-499 15-24% Moderate suppression Category 3Severe suppression
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< 750
< 15%
> 500
< 15%
< 200
< 15%
08 APR 2008
Table 2: 1994 Revised HIV pediatric classification system: Clinical categories
Category N: Not symptomatic Children who have no signs or symptoms considered to be the result of HIV infection or who have only one of the conditions listed in Category A
Category A: Mildly symptomatic Children with 2 or more of the following conditions but none of the conditions listed in categories B and C. - lymfadenopathy (≥ 0.5 cm at more than two sites; bilateral = 1 site) - hepatomegaly - splenomegaly - dermatitis - parotitis - recurrent of persistent upper respiratory infection, sinusitis or otitis media
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Table 2: 1994 Revised HIV pediatric classification system: Clinical categories
Category B: Moderately symptomatic Children who have symptomatic conditions, other than those listed for category A or category C, that are attributed to HIV infection. Examples of conditions in clinical category B include, but are not limited to, the following: - Anemia (<8gr/dl), neutropenia (<1000/mm³), or thrombocytopenia (<100000/mm³) for ≥ 30 dd - bacterial meningitis, pneumonia or sepsis (single episode) - candidiasis, orofaryngeal persisting for > 2 mm in children aged > 6 mm - cardiomyopathy - CMV infection with onset before age 1 month - diarrhea, recurrent or chronic - hepatitis, nephropathy - HSV stomatitis, recurrent (I.e. > 2 episodes/year) - HSV bronchitis, pneumonitis or esofagitis with onset before age 1 month - Herpes Zoster involving at least two distinct episodes or more than one dermatome - LIP or pulmonary lymphoid hyperplasia complex - ...
Category C: Severe symptomatic Children who have any condition listed in the 1987 surveillance case definition for acquired immunodeficiency syndrome, with the exception of LIP 16
08 APR 2008
Table 3:Association of baseline CD4 T cell % with long-term risk for death in HIVinfected children
DEA THS BASELINE < 5% 5%-9% 10%-14% 15%-19% 20%-24% 25%-29% 30%-34% ≥ 35%
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# PATIENTS 33 29 30 41 52 49 48 92
# 32 22 13 18 13 15 5 30
% 97 76 43 44 25 31 10 33
08 APR 2008
Table 4:Association baseline # HIV RNA Copy with long-term risk for death in HIVinfected children
DEA THS BASELINE
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≤ 4000 4001-50000 50001-100000 100001-500000 500001-1000000 ¾ 1000000
# PATIENTS 25 69 33 72 20 35
# 6 19 5 29 8 25
% 24 28 15 40 40 71
Total
254
92
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Table 5:Association baseline # HIV RNA copy & CD4 T cell % with long term risk for death in HIV infected children
DEA THS Baseline HIV RNA / Baseline CD4 T cell % ≤ 100000 ≥ 15% < 15% ¾ 100000 ≥ 15% < 15% 19
# PATIENTS
#
%
103 24
15 15
15 63
89 36
32 29
36 81
08 APR 2008
Table 8: Indications for initiation of antiretroviral therapy in children >12 mm with HIV infection (Nov 26,2003)
Clinical category
AIDS (Clinical cat. C)
Mild-moderate symptoms (Clinical cat. A or B) Asymptomatic (Clinical cat.N)
CD4+ Cell %
Recommendation
<15% (Immune cat. 3)
Any value
Treat
15-25% (Immune cat.2)
>= 100.000 c/ml
Consider treatment
OR
OR
>25% (Immune cat. 1)
AND 20
Plasma HIV RNA copy number
OR < 100.000 c/ml
AND
Many experts would defer therapy with closely FU 08 APR 2008
Concensus Belgian National Pediatric Group
< 6 mm of age: Start a treatment from the moment the infection has been confirmed by: - 2 positive elements: - Clinical status (Cat. C) - DNA-PCR - RNA-PCR - Culture - 2 positive virological results taken on 2 different samples
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Concensus Belgian National Pediatric Group
> 6 mm of age: decision to treat depends on clinical criteria and/or biological criteria - clinical: Cat. C and B (except 1 pneumonia) - immunological: - CD4 <20% if > 1y - CD4 <25% if < 1y - ⇓ abs. # CD4 ( >30% in <6months) - virological: - <1y: V.L. > 100.000 c/ml - >1y: V.L. > 150.000 c/ml 22
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What HAART to start with?
Nucleoside Reverse Transcriptase Inhibitors Non-Nucleoside reverse Transcriptase Inhibitors Nucleotide reverse transcriptase Inhibitors Protease Inhibitors Fusion Inhibitors 23
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Mechanism of action NRTI works here
PI works here Protease
NNRTI works here
Viral assembly Translation Protein cleavage
RNA and reverse transcription Transcription Injection of capsid contents
RNA DNA
Provirus (circular structure)
Integrase
Maturation
Integration of Provirus DNA into Host DNA
HIV particle
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Binding
FI works here
Completed HIV particle
Adapted from HIV/AIDS Handbook. 4th ed. Boston: Total Learning Concepts, 1999; Ritchie DJ. In: Powderly WG, 08 APR 2008 ed. Manual of HIV Therapeutics. Philadelphia: Lippincott-Raven, 1997:33-41.
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Concensus Belgian National Pediatric Group
< 6 mm of age: Î 2 NRTIs + NVP >6 mm of age: advanced stage:
- Cat. C - Immunological stage 3 - V.L. > 300.000 c/ml
Î 2NRTIs + 1 PI mild stage: Î 2NRTIs + 1 NNRTI 26
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“Doctors should pay attention with the fact that patients often lie when they are telling that they’ve taken their medication.” Hippocrates (460-377 BC)
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HIV in adolescents
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HIV in adolescents
Two Epidemiological Subgroups Adolescents: Behavioral vs perinatal Hallmarks of develoment: Adolescents vs Adult Differences in HIV Care Models: Pediatric vs. Adolescent vs. Adult Transition
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Two Epidemiologic Subgroups Adolescents
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Two Epidemiologic Subgroups Adolescents
Perinatally Infected with HIV Behaviorally Infected with HIV These two groups have both distinct as well as shared clinical and psychosocial characteristics
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Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Behavioral: more likely to be in earlier stages of HIV disease less OI complications no previous ARV exposure less likely to be resistant to ARV’s less likely to require HAART when HAART required can give simpler regimens treatment adherence problems may be relatively simpler to manage than perinatal group more likely to achieve functional autonomy 33
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Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Perinatal: more likely to be in more advanced stages of HIV disease and immunosuppression more likely to have hx of OI’s with complications/disabilities (eg. blindness, O2 dependent, chronic renal failure) more likely to have heavy ARV exposure hx therefore more likely to have multi-drug resistant virus more likely to require HAART to control viremia, low CD4 counts
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Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Perinatal (cont.): more complicated ARV regimens (eg. “mega-HAART”) more complicated non-ARV medications such as OI prophylaxis/treatment greater obstacles to achieving functional autonomy due to physical and developmental disabilities/greater dependency on family (eg. “adult” vulnerable child) when pregnant, higher risk of complications during more advanced stages of disease and of second generation HIV transmission due to multiple-drug resistance
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Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Mental Health Profile of Perinatally Infected Adolescents ADHD 15.9% Behavior Problems Psychiatric Dx
29%
17.4%
Perinatally infected adolescents also have a significant prevalence of residua of developmental delay and regression
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Hallmarks of development
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Hallmarks of development
Adolescent development and effect of HIV
– Independence – Body image – Peer relationships
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– Sexuality/Risk-taking – Future planning – Transitioning
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Autonomy and Independence Becoming an autonomous, self-directive person is a fundamental psychosocial task of adolescence. “I want to come to my appointments by myself”
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Body Image Adolescence is a time to define oneself; body image is in the forefront. “Am I developing normally?” “Do I look OK?” “Am I sexually attractive?”
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Peer Relationships The focus of adolescent relationships shifts from family to peers, and the peer group sets behavior standards. “Yeah I have a tattoo— all my girlfriends have one.”
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Sexuality Accepting one's physique Beginning to define self as a sexual being Forming new,more mature relations with both boys and girls Achieving masculine or feminine social role Preparing for commitment and family life “Nobody will love me— how will I tell them about my HIV?” 42
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Planning for the Future As abstract thinking develops, adolescents begin to plan for the future, defining their functional role in society, e.g. goals, education, job or career. “I’m older now— I actually have to do something with my life.”
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Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult
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Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Pediatric: family-centered and multidisciplinary care with pediatric expertise medical provider has more long standing relationship with care giver at home primary care approach integrated into HIV care issues of HIV disclosure to patient and youth’s confidentiality/right to consent care usually offered in discreet, child-friendly and intimate setting teen services supplemental to existing services 45
08 APR 2008
Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Adolescent: teen-centered and multidisciplinary care; provider may have minimal to no relationship with parent/care giver primary care approach integrated into HIV care youth often does not disclose HIV status to family issues of confidentiality and consent; care usually offered in discreet, teen-friendly and intimate setting teen services core to clinic-sexuality, pelvic examinations/Pap smears, STD screening and tx, reproductive health,substance use, rights to confidentiality and consent, treatment education and adherence approaches 46
08 APR 2008
Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Adult: adult-oriented care based on strict medical model Adult medical providers more often ID specialists than are pediatric or adolescent providers young person’s transitional issues usually not given any systematic specialized focus clinics tend to be very large and easy for transitioning patients to “slip through the cracks” unless very motivated
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Transition
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Transition
“Transition is a multifaceted, active process that attends to the medical, psychosocial, and educational or vocational needs of adolescents as they move from the child-focused to the adultfocused health-care system. Health care transition facilitates transition in other areas of life as well (eg. work, community, and school).” Reiss, J, Gibson R. Health Care Transition: Destinations Unknown. Pediatrics. 2002;110:1307-1314 49
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Transition
“Most developmental transitions create anxiety… timing of the transition will depend on developmental readiness, complexity of the health problems, characteristics of the adolescent and family, and the availability of skilled adult health providers. Transition is more complex and generally more difficult for those with more severe functional limitations or more complicated medical conditions.” Reiss, J, Gibson R. Health Care Transition: Destinations Unknown. Pediatrics. 2002;110:1307-1314 50
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Transition Recommendations Orient patients and families towards the future emphasizing long term survival Develop a transition plan early when it is still many years ahead Foster personal and medical independence early; children should assume some responsibility for their treatment at home and at school; adolescents should permitted and encouraged to participate in decision-making and consent
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Transition Recommendations Transition plans should be multifaceted and individualized: Medical: old provider should be familiar with new provider as clinician and the environment in which they provide care Mental health: goal should be to transition psychotherapy/psychiatric services simultaneously with medical services; often a challenge Psychosocial: housing/entitlements, health insurance should all be in place Life skills: educational goals, job training, parenting, etc. 52
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Transition
“Purposeful, planned movement of adolescents and young adults with chronic illness/disability from child-centered to adult oriented systems—health, employment, independent living.”
Transition is a process, not an event.
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MTCT prevention
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Inleiding
Samenwerking met ITG Opvolging van ong. 25 neonaten per jaar 80 % is Subsaharaans
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Invalshoek
Vrouw/moeder zijn als identiteit beinvloed door : • Serostatus • culturele verschillen
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Invloed: Cultuur - Serostatus individueel
relationeel
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maatschappelijk
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Hoe uit zich dat in de praktijk?
Achterdochtig! gaan ze me anders benaderen? hoe gaan ze mijn kind verzorgen?
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Bezoek op de kraamafdeling na de geboorte van de baby Kraambezoek buiten de bezoekuren omwille van geheimhouding
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Info over testen van de baby Dag van de hielprik (D3-5) Op 1 – 3 – 6 – 12 – 18 maanden
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Retrovir medicatie baby vraagt discipline vragen rond bijwerkingen vragen van omgeving tip voor verplegend personeel 62
08 APR 2008
Geen borstvoeding moeilijk te verwerken vragen van omgeving Borstvoeding is gratis <=> melkvoeding kost extra geld
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Regelzaken
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geboorteaangifte mutualiteit voor baby regelen kraamgeld, kinderbijslag babyvoeding via Kind en gezin (speciale regeling) kraamhulp kinderopvang problemen rond illegaliteit woningproblemen enz….
08 APR 2008
Opvolgen van consulten PCR-testen = polymerase chain reaction test
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1 maand 3 maanden 6 maanden 12 maanden
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Hiv-serologie : Elisatest 12 maanden 18 maanden
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Follow-up tot 5 jaar Opvolgen van psychomotorische ontwikkeling
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Protocol Preventie Perinatale transmissie
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PRENATALE LUIK Indicatie om moeder te behandelen met HAART : CD4 < 300/mm3 of virale lading > 5000 copies/ml of klinisch stadium B of C Behandeling : Starten met Retrovir, Epivir en PI liefst na de 14 de week zwangerschap (14-28 w) in samenspraak met gespecialiseerd centrum
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PERINATALE LUIK: MOEDER
De beslissing omtrent vaginale bevalling en sectio wordt in overleg genomen tussen de behandelende hiv-arts en gynaecoloog Belangrijke factoren hierin zijn :
de behandeling van de moeder laatste bloedwaarden (virale lading) voorziene verloop van bevalling (primepara, meerdere zwangerschappen, grootte van het kind..) 70
08 APR 2008
Vaginale bevalling
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toediening van Retrovir T.H.I.V. (1 flac. = 200mg/ml)
oplaaddosis : bij start van de arbeid 2mg Retrovir/kg in glucose 5% - 250 cc
onderhoudsdosis : 1mg Retrovir/kg in glucose 5% - 250 cc over 1 u voor de verdere periode van arbeid (kan 24 u of langer) tot aan het afklemmen van de navelstreng 08 APR 2008
Sectio caeserae
oplaaddosis : 2mg Retrovir/kg in glucose 5% - 250 cc starten 3 uur voor de ingreep
onderhoudsdosis : 1mg Retrovir/kg in glucose 5% - 250 cc over 1 u bij het starten van de ingreep tot aan het afklemmen van de navelstreng. Best op voorhand klaar maken en meegeven naar O.K.
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PERINATALE LUIK: BABY
geen borstvoeding : preventie transmissie moeder – kind
toediening van Retrovir orale suspensie (1 fles = 200 ml, 10mg/ml) dosis : 2mg/kg, 4 x /dag starten 8 à 12 u na de geboorte gedurende 6 weken bv. baby van 3000 gr krijgt 0,6 ml Retrovir per os 4 x per dag 73
08 APR 2008
PERINATALE LUIK: BABY Indien Retrovir IV toegediend dient te worden bij neonaten is de dosis : 1,5 mg/kg IV 4x/dag Dosages Retrovir dienen aangepast te worden bij prematuriteit: 1,5 mg/kg IV of 2 mg/kg PO 2x/d, en na 2 weken verhogen naar 3x/d (bij neonaten > of = 30 ww GA) of na 4 weken verhogen naar 3x/d (bij neonaten < 30 ww GA) 74
08 APR 2008
Viramune protocol Viramune moet toegediend worden, onafhankelijk van voorafgaande behandelingen, indien de laatste virale lading hoger is > 10.000 copies/ml of wanneer de zwangerschap niet goed opgevolgd werd bv.laattijdige screening, geen behandeling en hoge virale lading moeder : Viramune 2OO mg in 1 dosis bij het begin van de arbeid of voor de keizersnede kind :
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Viramune 2mg/kg in 1 dosis tussen de 48 – 72 uur na de geboorte, bij de normale Retrovirbehandeling Gedurende 1 week Epivir toedienen 2mg/kg/d
08 APR 2008
POSTNATALE LUIK: BABY Geen testing nodig op navelstrengbloed : geeft vals positieve resultaten voor HIV Veneuze bloedafname bij baby zeker :
PCR test op dag van de hielprik (vanaf dag 3 t.e.m 5) type HIV (1 of 2) van moeder op aanvraag schrijven + naam van de moeder 1 x 1 tube EDTA 2,7 ml
Bloedstalen na afname direct naar labo brengen. 76
08 APR 2008
Afspraak maken voor follow-up 1 maand na geboorte bij Dr. Maes Verdere Retrovirbehandeling 2mg/kg 4 x per dag, als PCR na 4 weken negatief is kan behandeling na 6 weken worden stopgezet geen borstvoeding, dient uitgebreid besproken te worden, in sommige culturen wordt er een groot belang aan gehecht
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ITG Kronenburgstraat 47 2000 Antwerpen Dr. Kint I., aidsrevalidatiearts Hemelaar Eva, sociaal verpleegkundige tel : 03.247.64.65 CBSK Lindendreef 1 2020 Antwerpen Dr. Maes P, kinderarts Myriam Willems, sociaal verpleegkundige tel : 03.280.21.13 78
08 APR 2008
