Hiv in children & adolescents and pMTCT · Dr. P. Maes – M. Willems – K ... HIV/AIDS resource center for women: ... Initiate therapy, regardless of age or symptom status 2. Defer

Hiv in children & adolescents

and pMTCT

Dr. P. Maes – M. Willems – K. De Winter: UZA

Dr. I. Kint: ITG

HIV

HIV

PART 1: pMTCT Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

HIV


Newborn

Formula feeding AZT sirop during 6 weeks: 4 mg/kg/dosage every 12 hours, from 8-12 hours after birth

until the age of 6 weeks; adapted dosages when prematurity But when the mother:

Didn’t have therapy Had a bad compliance

Then combination therapy (Haart) is needed for the baby Controls at 1m (PCR), 3m (PCR), 6m (PCR), 12m (Sero) and

… if necessary also at 18m (Sero)

European collaborative study: Trends over time in

mode of delivery

0

10

20

30

40

50

60

70

80

1997 1998 1999 2000 2001 2002 2003

%

elective Csection emergency Csection Vaginal delivery

European collaborative study: Trends over time in

vertical transmission rates

14,5

8,5

5,4

2,2

0,7

13,713,4

0

2

4

6

8

10

12

14

16

85-87 88-90 91-93 94-96 97-99 00-03 04_14

%

HIV


Websites

http://www.bhiva.org: British HIV Association: guidelines for the management of HIV infection in pregnant women 2008

http://www.hivandhepatitis.com/recent/women/womenandhiv/WomenHIV_part_1.pdf also part 2 and part 3: very nice , focus on the US

http://hab.hrsa.gov/publications/womencare05/index.htm : A guide to the clinical care of women with HIV

HIV/AIDS resource center for women: http://www.thebody.com/content/art44411.html

Treatment Guidelines: http://www.aidsinfo.nih.gov/Guidelines/Default.aspx?MenuItem=Guidelines

Scientific Institute of Public Health, Belgium: http://www.iph.fgov.be/epidemio/epinl/index19.htm

Breach:

http://www.breach-hiv.be/p_243.htm

http://www.bhiva.org/

http://www.hivandhepatitis.com/recent/women/womenandhiv/WomenHIV_part_1.pdf




http://hab.hrsa.gov/publications/womencare05/index.htm



http://www.thebody.com/content/art44411.html



http://www.aidsinfo.nih.gov/Guidelines/Default.aspx?MenuItem=Guidelines

http://www.aidsinfo.nih.gov/Guidelines/Default.aspx?MenuItem=Guidelines

http://www.iph.fgov.be/epidemio/epinl/index19.htm








36.7 million [34.0 million – 39.8 million] 31.8 million [30.1 million – 33.7 million] 16.0 million [15.2 million – 16.9 million] 3.2 million [2.9 million – 3.5 million]

2.1 million [1.9 million – 2.4 million] 1.9 million [1.7 million – 2.1 million] 240 000 [210 000 – 280 000]

1.1 million [940 000 – 1.3 million] 1.0 million [1.2 million – 1.5 million] 190 000 [170 000 – 220 000]

Number of people

living with HIV in 2015

People newly infected

with HIV in 2015

AIDS deaths in 2015

Total Adults

Women Children (<15 years)

Total Adults

Children (<15 years)

Total Adults

Children (<15 years)

Global summary of the AIDS epidemic

Source: UNAIDS/WHO estimates.

http://www.who.int/en/

Decline in HIV incidence and mortality over time

0

500 000

1 000 000

1 500 000

2 000 000

2 500 000

3 000 000

3 500 000

2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

People dying from AIDS-related causes globally

People newly infected with HIV/AIDS globally



Number of people newly infected with HIV


The red shading shows future targets.


Number of people dying from HIV


The red shading shows future targets.


HIV-plan EU-report on the AIDS epidemic

HIV-plan BE-report on the AIDS epidemic

Official presentation on 15/10/13 Aims of the HIV plan: - First target: Prevention - Second target: Screening - Third target: Taking care of people with HIV - Fourth target: Daily living of people with HIV

New HIV Plan in Belgium: 2014 -2019






Child with HIV or risc of infection with HIV: What to do?

First… Diagnose!

ELISA Western Blott PCR viral load

Then…Start treatment? And when? And how?

HAART

Highly Active Anti Retroviral Therapy

Dramatic fall in child and adult mortality from HIV infection in Europe

Very expensive major impact on the family Wide variation in prescribing practice across

Europe: from 50% to 97% in different countries Problems of compliance/adherence

When to start a treatment with HAART ?

When to start a treatment with HAART ?

- No randomised trial evidence is available in children

- 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 ?

HAART guidelines for 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 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

Basic principles for HAART in HIV + children

1. Importance of clinical trials in children

2. Management of prescribing HAART is becoming increasingly complex and should wherever possible be directed in specialised centres by a multidisciplinary team

3. Regular monitoring (clinical/biochemical/psycho-social)

Basic principles for HAART in HIV + children

4. Factors to be considered before starting HAART:

- availability, tolerability, efficacy, formulation, and side effect profile of currently available drugs, including dosage frequency, and impact on school, family, and social life

- dosage in function of the farmaco-kinetic, complex

differences in absorption, distribution and metabolism between neonates, infants, children, adolescents and adults

Personal conclusions HAART in HIV + children

HAART, 95% compliance necessary

50% success is very good

universal problem

motivation if you try to get ideality, you get reality

if you try to get reality, you get shit hit hard, hit early

compliance - adherence - ?

Another way to look at it: “living met HIV”

Personal conclusions HAART in HIV + children

Bad taste of the medication

Difficult medicationscheme

Food advise

Quantity of pills, size of pills

Adverse events

Child

Adaption of living to the medication scheme

Environment is not aware of the diagnosis

Therapy duration

Personal conclusions adherence in HIV + children

daily confrontation with sickness daily struggle with the medication altered motivation when the child is going better Child is sometimes to young to understand the necessity of

the medication QOL/Sleep/rest The weather / Seasons Fight with partner Relation doctor- patient Function of the multidisciplinary team Accesability of the hospital Influence of alternative medicines, healers, religious

leaders, gossip in the community

“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)

Natural evolution of HIV infection ?

And now…Start treatment? when? and how?

Table 1: 1994 Revised HIV pediatric classification system:

Immune categories based on Age-specific CD4+ T-cells count and

percentage

<12 months 1-5 years 6-12 years

Immune category No./µL % No./µL % No./µL %

Category 1-

No suppression 1500 25% 1000 25% 500 25%

Category 2-

Moderate suppression

750-1499 15%-24% 500-999 15%-24% 200-499 15-24%

Category 3-

Severe suppression

< 750 < 15% > 500 < 15% < 200 < 15%


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


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

Table 3:Association of baseline CD4 T cell % with long-term risk for

death in HIV- infected children

DEA THS

BASELINE # PATIENTS # %

< 5%

5%-9%

10%-14%

15%-19%

20%-24%

25%-29%

30%-34%

35%

33

29

30

41

52

49

48

92

32

22

13

18

13

15

5

30

97

76

43

44

25

31

10

33

Table 4:Association baseline # HIV RNA Copy with long-term risk for

death in HIV-infected children

DEA THS

BASELINE # PATIENTS # %

4000

4001-50000

50001-100000

100001-500000

500001-1000000

1000000

Total

25

69

33

72

20

35

254

6

19

5

29

8

25

92

24

28

15

40

40

71

36

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 %

# PATIENTS # %

100000

15%

< 15%

100000

15%

< 15%

103

24

89

36

15

15

32

29

15

63

36

81

Table 6: Indications for initiation of antiretroviral therapy in children

with HIV infection

Clinical symptoms associated with HIV infection (cfr Tabel 2: Clinical cat. A,B or C)

Evidence of immune suppression, indicated by CD4 T cell absolute number of percentage (Cfr. Table 1: Immune cat. 2 or 3)

Age < 12 mm, regardless of clinical, immunologic or virologic status

For asymptomatic children aged 1 year with normal immune status, two options can be considered:

1. Initiate therapy, regardless of age or symptom status

2. Defer treatment in situations in which the risk for clinical disease progression is low and other factors favor postponing treatment. In such cases, the health care provider should regularly monitor virologic, immunologic, and clinical status. Factors to be considered in deciding to initiate therapy include the following:

- High or increasing HIV RNA copy number

- Rapidly declining CD4 T cell number or percentage to values approaching those indicative of moderate immune suppression (Cfr. Table 1: Immune cat. 2)

- Development of clinical symptoms

Until 2016…Start treatment? when? and how?

Tabel 8: Indications for initiation of antiretroviral therapy in

children >12 mm with HIV infection

Clinical categoria CD4+ Cell % Plasma HIV RNA

copy #

Recommandation

AIDS

(Clinical cat. C)

<15%

(Immuun cat. 3)

Any VL Treat

Mild

symptomatic(Clinical

cat. A or B)

15-25%

(Immuun cat.2)

>= 100.000 c/ml Consider treatment

Asymptomatic

(Clinical cat.N)

>25%

(Immuun cat. 1)

< 100.000 c/ml Many experts would

rather wait to start a

treatment, but with

close FU

OR

OR OR

AND AND

Until 2016…Start treatment? when? and how?

And now 2017…Start treatment? … when?

Based on data from the multinational START and PENPACT1 trials, the Panel now recommends antiretroviral treatment (ART) for all HIV-infected children, regardless of clinical symptoms, viral load or CD4 T lymphocyte (CD4) count. The strength of the Panel's recommendations varies by age and pretreatment CD4 cell count due to fewer available pediatric data regarding benefits and risks of therapy in asymptomatic HIV-infected children than in adults. The text offers guidance on the urgency of initiation of ART based on age, clinical status and CD4 cell counts.

And now 2017…Start treatment? … when?

And now 2017…Start treatment? … how?

What Drugs to Start: Initial Combination Therapy for Antiretroviral Treatment-Naive Children Content has been reorganized to enhance usability, and a figure has been added to provide an overview of Preferred and Alternative regimens for initiation of ART in treatment -naive children .

https://aidsinfo.nih.gov/guidelines/html/2/pediatric-arv-guidelines/444/regimens-recommended-for-initial-therapy-of-antiretroviral-naive-children

And now 2017…Start treatment? … how?

The Panel has added the tenofovir alafenamide (TAF) containing fixed dose combination tablet elvitegravir/cobicistat/emtricitabine/TAF (Genvoya) as a preferred integrase strand transfer inhibitor (INSTI) regimen in adolescents 12 years and older. Darunavir boosted with ritonavir is now considered a preferred protease inhibitor (PI) in children and adolescents aged 3 years and older. Dolutegravir is now considered a preferred INSTI in adolescents aged 12 years and older. Raltegravir is now considered a preferred INSTI in children aged 2 to 12 years. The Panel has determined that fosamprenavir, nelfinavir, stavudine, and unboosted atazanavir should not be used for initial therapy.

What HAART to start with?


Nucleoside Reverse Transcriptase Inhibitors

Non-Nucleoside reverse Transcriptase Inhibitors

Nucleotide reverse transcriptase Inhibitors

Protease Inhibitors

Integrase Inhibitors

Fusie Inhibitors


Workingmechanisms

NNRTI work here

PI work here

RNA and reverse transcription

Injection of capsid contents

HIV particle Binding Completed HIV particle

Maturation

Viral assembly

Protease

Translation

Protein cleavage

Integrase

Transcription

RNA DNA Provirus (circular

structure)

Integration of Provirus DNA into Host DNA

NRTI work here

FI work here




HIV


Care and treatment support of

HIV-Infected Adolescents

http://www.google.be/url?sa=i&rct=j&q=&esrc=s&source=images&cd=&cad=rja&uact=8&ved=0ahUKEwi238-Lw5TKAhWD9g4KHS1XAZ8QjRwIBw&url=http://www.hivguidelines.org/clinical-guidelines/adolescents/transitioning-hiv-infected-adolescents-into-adult-care/&psig=AFQjCNE0KIqrI4-xCy1fkPHXyIStZ3ipug&ust=1452146942012198

Topic outline

Two Epidemiological Subgroups Adolescents:

Behavioral vs perinatal

Differences in HIV Care Models:

Pediatric vs. Adolescent vs. Adult

Transition

Local experience

19 DEC 2014

Two Epidemiologic Subgroups Adolescents

19 DEC 2014

Two Epidemiologic Subgroups Adolescents

19 DEC 2014

1. Perinatally Infected with HIV

2. Behaviorally Infected with HIV

These two groups have both distinct as well

as shared clinical and psychosocial characteristics

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

Perinatal:

more likely to be in more advanced stages of HIV disease and immunosuppression

more likely to have OI’s with complications/disabilities (eg. blindness, O2 dependent, chronic renal failure)

more likely to have heavy ARV exposure and therefore more likely to have multi-drug resistant virus

more likely to require HAART to control viremia, low CD4 counts



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)

significant prevalence developmental delay and regression (eg. ADHD 15% - Behavioral problems 29%)

when pregnant, higher risk of complications during more advanced stages of disease and of second generation HIV transmission due to multiple-drug resistance



Differences in HIV Care models:


19 DEC 2014



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



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, rights to confidentiality and consent, treatment education and adherence approaches



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

Transition

Transition

19 DEC 2014

“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 adult-

focused 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

Transition

19 DEC 2014

“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

Principles of Healthcare Transition

Begin healthcare transition early

Continuity of care is the goal

Transition planning should be comprehensive

Involve teen and family

Providers and parents should be prepared to facilitate movement

Service coordination, communication and collaboration between providers is essential

Transition

Interventions & Strategies

Maintain a relationship with teen and family

Stimulate discussion about teen’s future

Understand the nature and implications of teen’s chronic illness

Determine time for transition discussions based on teen's development and needs

Practice family-centered care

Transition

What can young people do?

Start talking about upcoming transition

Acknowledge and accept developmental change

Accept adulthood responsibly

Take charge of healthcare information

Transition

HIV


CBSK since 1990

Total seropositive “children” in FU = 96

2016 seropositive “children” in FU = 27

Perinatal/behavioral = 27/03

Total MTCT in FU > 500

2016 MTCT in FU = 91

Local experience

CBSK in 2017

Local experience

PATIENTS

< 14Y = 7/27 HAART: 6/7

14 -16Y = 4/27 HAART: 3/4

16 -18Y = 5 (à 8)/27 HAART: 4/5

> 18Y = 11/27 HAART: 11/11

CBSK in 2017

Local experience

TRANSITIONS TO PLAN

2015 = 4/27

2016 = 4/23

2017 = 3/19 (waarvan 1 naar Gent)

2018 = 2/16

2019 = 3/14 (waarvan 2 naar Gent)

2020 = 3/11 (waarvan 1 naar Brugge)

Hiv in children & adolescents and pMTCT · Dr. P. Maes – M. Willems – K ... HIV/AIDS resource center for women: ... Initiate therapy, regardless of age or symptom status 2. Defer

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