Women, children,

1
Women, children, Family care

• Margaret Siwale, MD , PediatricianLusaka Trust
  Hospital, Zambia
• Sibyl Geelen, MD,PhD , Ped Infect Dis Specialist
  CCPD/PharmAccess Foundation UMCU,The
  Netherlands

2

• Case Mrs M and her children

3
Jeannie, 3 years old

• Condition deteriorated in the last few months
• Recurrent pneumonia, bouts of diarrhoea and
  weight loss
• Tested for HIV rapid test positive
• CD4 T-cell count 285/mm3 (11 ).

4
Jeannies brother Bruno, 1 year old

• Skinny infant
• Oral candidiasis recently
• Persistent diarrhoea
• Not tested for HIV yet
• Social situation
• Father died last year
• Mother sells vegetables at the market
• During daytime, kids are taken care of by
  grandmother

5

• How would you diagnose HIV infection in Bruno in
  your setting?
• How do you decide whether Jeannie and/or Bruno
  need antiretroviral therapy?

6

• Staging of HIV/AIDS in children and infants
• Two different classification systems
  WHO CDC

7
Revised WHO staging 2005 Which changes were
made with regard to the classification of infants
and children?
www.who.int/HIV/pub/guidelines/clinicalstaging.pdf
WHO/HIV/2005.02
8
Both clinical and immunological classification
have been modified

• Clinical staging ? 4 stages (previously 3)
• Immunologic staging ? 4 stages (previously 3)

9
WHO pediatric clinical staging

• WHO Clinical Stage 1
• Asymptomatic
• PGL (Generalized lymphadenopathy)
• WHO Clinical Stage 2
• Hepatosplenomegaly
• Papular pruritic eruptions
• Seborrhoeic dermatitis
• Extensive human papilloma virus infection
• Extensive molluscum contagiosum
• Fungal nail infections
• Recurrent oral ulcerations
• Lineal gingival erythema (LGE)
• Angular cheilitis
• Parotid enlargement
• Herpes zoster
• Recurrent or chronic RTIs (otitis media,
  otorrhoea, sinusitis)

SourceInterim WHO clinical staging of HIV/AIDS
and HIV/AIDS case definitions for surveillance
(WHO/HIV/2005.02)
10
WHO pediatric clinical staging (contd)

• WHO Clinical Stage 3
• Conditions where a presumptive diagnosis can be
  made on the basis of clinical signs or simple
  investigations
• Moderate unexplained malnutrition not adequately
  responding to standard therapy
• Unexplained persistent diarrhoea (14 days or
  more )
• Unexplained persistent fever (intermittent or
  constant, for longer than one month)
• Oral candidiasis (outside neonatal period )
• Oral hairy leukoplakia
• Acute necrotizing ulcerative gingivitis/periodont
  itis
• Pulmonary TB
• Severe recurrent presumed bacterial pneumonia
• Conditions where confirmatory diagnostic testing
  is necessary
• Chronic HIV-associated lung disease including
  brochiectasis
• Lymphoid interstitial pneumonitis (LIP)
• Unexplained anaemia (lt8g/dl), and or neutropenia
  (lt1000/mm3) and or
• thrombocytopenia (lt50 000/ mm3) for more than
  one month

11
WHO pediatric clinical staging (contd)

• Clinical Stage 4
• Conditions where a presumptive diagnosis can be
  made on the basis of clinical signs or simple
  investigations
• Unexplained severe wasting or severe malnutrition
  not adequately responding to standard therapy
• Pneumocystis pneumonia
• Recurrent severe presumed bacterial infections
• e.g. empyema, pyomyositis, bone or joint
  infection, meningitis, but excluding pneumonia
• Chronic herpes simplex infection
• orolabial or cutaneous of more than one months
  duration
• Extrapulmonary TB
• Kaposis sarcoma
• Oesophageal candidiasis
• CNS toxoplasmosis (outside the neonatal period)
• HIV encephalopathy

12
WHO pediatric clinical staging (contd)

• Clinical Stage 4 (Cont)
• Conditions where confirmatory diagnostic testing
  is necessary
• CMV infection
• CMV retinitis or infection of organs other than
  liver, spleen or lymph nodes onset at age one
  month or more)
• Extrapulmonary cryptococcosis including
  meningitis
• Any disseminated endemic mycosis
• (e.g. extrapulmonary histoplasmosis,
  coccidiomycosis, penicilliosis)
• Cryptosporidiosis
• Isosporiasis
• Disseminated non-tuberculous mycobacteria
  infection
• Candida of trachea, bronchi or lungs
• Visceral herpes simplex infection
• Acquired HIV-associated rectal fistula
• Cerebral or B cell non-Hodgkin lymphoma
• Progressive multifocal leukoencephalopathy (PML)
• HIV-associated cardiomyopathy or HIV-associated
  nephropathy

13
Revised WHO pediatric immune classification CD4
count and percentage of total lymphocytes
Source WHO Antiretroviral treatment of HIV
infection in infants and children in resource
limited settings, towards universal access
recommendations for a public health approach
(2005 revision) Draft October 2005
14
Remember

• In using CD4 count or for HAART decision
• use age-appropriate levels !

15
Case contd

• Jeannie aged 3 years
• WHO clinical stage 3
• CD4 285/mm3 (11)
• Strategy ?

16
WHO Criteria to start HAART in childrenRevised
draft version Oct 2005

• ? Treat irrespective of CD4-T cell or count
• ? HAART indicated for majority of children
  However, in children gt18 months with -
  pulmonary TB, - lymphocytic interstitial
  pneumonia (LIP), - oral hairy leukoplakia, -
  or thrombocytopenia, HAART may be deferred if
  CD4 values are above the threshold values to
  initiate HAART

• WHO stage 4
• WHO stage 3

Source Modified from Interim WHO clinical
staging of HIV/AIDS and HIV/AIDS case definitions
for surveillance (WHO/HIV/2005.02) and
Antiretroviral treatment of HIV infection in
infants and children in resource limited
settings, towards universal access
recommendations for a public health approach
(2005 revision, draft October)
17
WHO Criteria to start HAART in childrenRevised
draft version Oct 2005

• WHO stage 2 and 1

• ? Use CD4-T cell or count to guide decisions on
  ART initiation
• For those settings where CD4-T cell count is not
  available WHO also provides values on total
  lymphocyte counts

Source Modified from Interim WHO clinical
staging of HIV/AIDS and HIV/AIDS case definitions
for surveillance (WHO/HIV/2005.02) and
Antiretroviral treatment of HIV infection in
infants and children in resource limited
settings, towards universal access
recommendations for a public health approach
(2005 revision, draft October)
18
Case contd

• Bruno aged 1 year
• HIV rapid test
• No HIV-PCR testing available
• CD4 count 350/mm3 (15)
• Strategy ?
• what would you do if you do not have access to
  CD4 determination ?

19
A presumptive diagnosis of severe HIV disease in
infants and children aged under 18 months in
situations where virological confirmation of HIV
infection is not available, should be made if

• Infant is confirmed HIV-antibody positive
• Aged under 18 months and
• Symptomatic with two or more of the following
  clinical signs- oral thrush (candidiasis)-
  severe pneumonia- severe wasting/malnutrition
• - severe sepsis
• Other factors that support the diagnosis of
  severe HIV disease in an HIV seropositive infant
  include
• - recent HIV related maternal death or -
  advanced HIV disease in the mother- CD4-T cells
  lt 25
• Confirmation of the diagnosis of HIV infection
  should be sought as soon as possible

Source Modified from Interim WHO clinical
staging of HIV/AIDS and HIV/AIDS case definitions
for surveillance (WHO/HIV/2005.02) and
Antiretroviral treatment of HIV infection in
infants and children in resource limited
settings, towards universal access
recommendations for a public health approach
(2005 revision, draft October)
20

Without Antiretroviral Treatment
Kids have a POOR PROGNOSIS HIV infection
progresses more rapidly than in adults in 2005
? 560,000 children died
21
Poor prognosis in HIV-1 infected African infants
52,5
11
7.6

• n3,468 children pooled analysis of 7
  clinical trials in sub-Saharan Africa

Newell,Lancet 2004361236-43
22
Steps to successful HAART in children
What issues are important to discuss check
before initiating HAART in children?
23
Steps to successful HAART in children

• Child
• HIV diagnosis confirmed?
• Comprehensive clinical and laboratory assessment
• WHO or CDC classification
• Is the child eligible for antiretroviral therapy
  according to the WHO or CDC criteria?

24
Steps to successful HAART in children

• Mother/caregiver
• Has the mother/caregiver received information on
  ARVs, expected outcomes, potential side
  effects?
• Does the mother appreciate the need for
  intensivemonitoring and follow-up?
• Has the importance of adherence been discussed?
• Have barriers to adherence been discussed
  andresolved as far as possible? (if needed with
  support of community support groups)

25
Which obstacles do you encounter most frequently?
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Assess patient family readiness

• Potential barriers..
• Has the mother disclosed HIV status to anyone?
• Do the other people in the household know about
  the childs diagnosis?
• Is there support in the household/family?
• Is the living situation stable?
• Other

27
Assess patient family readiness

• Who will give the medications to the child?
• Does this person know when/how much to give?
• Does the caregiver recognize the need for the
  child to take ARV for life, even if they have no
  symptoms or feel better?
• Does the caregiver have an understanding of the
  importance of poor adherence and the consequences

• Does the caregiver have a plan for when to give
  ARV and how not to miss doses?
• Has the child tasted the medications?
• How does the childs developmental level
  influence ability to take medications?
• Has the health provider observed the
  administration of medication?

28
Involvement of another caregiver to support the
mother or guardian at initiation of therapy
appears to be critical to the success of the
therapy
29
Remember
ARV therapy is rarely an emergency !
30
Remember

• Children are dependent upon adults to administer
  or supervise administration of their medications
• Children can exert considerable influence on
  adherence dependent upon developmental stage
• spitting, vomiting, refusing, running away
• Healthcare providers need to teach families
  techniques to give medication to young children

31

• Which regimen would you prescribe for Jeannie
  and/or Bruno in your setting ?

32
Most frequently used first line HAART

• Zidovudine or Stavudine plus Lamivudine
• plus
• Nevirapine or Efavirenz (children gt 3 yrs)

33
HAART in children
What to expect ?
34
Response to HAART in children

• Usually good clinical response
• Usually good recovery of immune
• system, better than in adults
• Variable virologic response
• Continued support of the family is essential
  (multidisciplinary team)

35

• 660,000 children are in need of treatment
• 40 less than 18 months of age
• Only 20,000-25,000 receive therapy
• Why arent more children receiving ARVs ?

36
Obstacles

• Availability of pediatric medication
• costs formulations
• Diagnosis in infants lt 18 months
• tests expensive and complicated
• Expertise of health care workers
• Social and political issues

37
Pediatric medication

38
Problems with liquids in resource limited settings

• Cost
• Price 3-10 times higher, not affordable in many
  settings
• In practice half as many children as adults
  treated for the same budget
• Practical
• Not all antiretrovirals exist in liquid form
• Liquids can be cumbersome ? difficult to store,
  handle, transport
• Large volumes, poor taste
• Some liquids have to be kept cold

39
Pills/Tablets

• No fixed dose tablets for babies and
  children
• Adult tabs are broken in ½ and ¼ (or even
  smaller parts)
• Probably okay for older children
• Risk of under-or overdosing in infants

40
Pedimmune

• Pediatric version of adult Triomune (d4T,3TC,NVP)
• Junior and Baby
• On the market in 2006 ?

child
baby
Adult
41
Expertise of healthcare workers

42
GPs generally shy away from treating
children incorrectly believing that they cannot
properly treat children

Timothy Meade, GP in Lusaka
43
Day care, Lusaka
Courtesy of Dr Timothy Meade, Lusaka, Zambia
44
Social and Political obstacles

45

• Both policy makers and caregivers are often
  unconvinced that antiretroviral therapy works in
  children!
• Stigma and secrecyThe disease of shame

46
Case contd

• Both children start HAART
• How would you organize follow-up?

47
Remember

• Always assess knowledge
• Always calculate and recalculate drug dosages
  based on weight, size and/or age
• Constantly assess adherence
• Anticipate non-adherence during crisis periods
  for the patients
• Sustain supportive activities
• Support family adherence efforts at every step
• Dont forget to share and celebrate treatment
  successes

48

• Mrs M, mother of the family

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Mrs M, 26 years old

• Suffered from recurrent thrush
• Pneumonia twice in the previous 2 years
• Knows that she is HIV positive since 1 year
• Now 2 months pregnant
• Worried that the baby will be infected
• Hasnt informed her new partner about the HIV
  infection

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Mrs M

• Which issues do you consider to be
• important to discuss with Mrs M
• at this stage ?

51
Mrs M

• Education and counselling
• Medical ? Staging
• Social ? Disclosure

52

• Mrs M has WHO stage 2
• CD4 150/mm3
• Strategy ?
• Mrs M needs HAART for her own health

Best timing of HAART ? Remember shes 2 months
pregnant
53

• Preferably start HAART at 14 weeks (after first
  trimester)
• BUT first check readiness
• Continue HAART after birth yes
• Prophylaxis for the baby yes (to follow)

54
Suppose

• Mrs M has WHO stage 2 CD4 420/mm3
• Strategy ?
• HAART not yet indicated for her own health
• What would you recommend for PMTCT ?

55
What does WHO currently recommend ?

• Existing and upcoming guidelines will not
  recommend HAART in this situation
• but
• They will also not definitely recommend against
  it

56
WHO adviceIf capacity to deliver full range of
ARVs

• Mother
• Pregnancy start AZT at wk 28 or as soon as
  feasible thereafter
• Intrapartum continue AZT single dose NVP
  consider 3TC
• Postpartum continue AZT 3TC for 7 days
• Infant single dose NVP AZT 7 days

57
WHO adviceIf capacity to deliver only minimum
range of ARVs for PMTCT (e.g no AZT available)

• Mother
• Pregnancy nothing
• Intrapartum single dose NVP
• Postpartum nothing
• Infant single dose NVP

High percentage of NVP resistance in both women
and infants will occur
58
Thus

• Choice of PMTCT regimen (HAART or other PMTCT
  regimen)
• will depend on local circumstances and national
  guidelines

59

• After Mrs M has given birth what
  infant-feeding practice would you recommend?

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Infant feeding

• Increases risk of transmission of HIV by 10-20
• Lack of breast feeding can expose children to
  risks of malnutrition or infections
• In the village, not breast feeding brings stigma
• Striking a balance is quite complicated
• Good and effective counselling essential
• Need to consider the risk and benefits according
  to the situation

61
Are there options to prevent postpartum
transmission if substitute feeding is not
possible ?

• Under investigation
• Effect of continued maternal HAART while
  breastfeeding (Bultereys JID 2005192)
• Prolonged ARV prophylaxis in the infant while
  being breastfed (SIMBA study, not published
  yet)

62
In summary the challenges

• Advocacy- keep children on the agenda
• Improve knowledge and expertise on pediatric ART
• Encourage uptake of children in programmes
• Recognize the special needs of children
• Assert pressure for development of affordable
  pediatric formulations
• Maximize efforts to reduce mother-to-child
  transmission