Pediatric HIV/AIDS

Workeabeba Abebe (MD,MPH)Assistant Professor of PediatricsDepartment of Pediatrics and Child HealthAAU, Faculty of Medicine

AUg, 2011

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Objectives

• Epidemiology and mortality statistics for pediatric HIV

• Factors that contribute to mortality of pediatric HIV

• Staging criteria for Pediatric HIV• WHO and CDC guidelines

• Clinical presentation of Pediatric HIV• Management of Pedi. HIV

Historical Perspective of Pediatric HIV: Sub-Saharan Africa

• 1983-1985 the first cases of pediatric HIV were first observed in Rwanda, the Democratic Republic of Congo, and Uganda

• Mid 1980’s longitudinal cohort studies started in East Africa (Kigali, Kampala, Kinshasha, Nairobi) to study maternal to child transmission and the natural history of HIV-exposed and infected children

• In 1988 the first specialist clinic started in Uganda

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Historical perspective of pediatric HIV: Ethiopia • The first HIV exposed newborn was identified in 1986

• Prior to 2002 pediatric HIV care was limited to provision of cotirmoxazole preventive therapy &other supportive care

• Free ARVs were made available between 2002- 2003.In few private institutions and government hospitals selected pediatric AIDS cases were treated with crushed adult tablets.

• In 2005 pediatric ARV formulations were available on free basis and since then pediatric ART service has expanded to many health institutions

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Estimated Number of ChildrenLiving with HIV/AIDS in 2005

Western & Central Europe

40004000[<8000][<8000]

North Africa & Middle East

31 00031 000[12 000 – 75 000][12 000 – 75 000]

Sub-Saharan Africa

2.0 million2.0 million[1.5 – 3.0 million][1.5 – 3.0 million]

Eastern Europe & Central Asia

6900 6900 [3400 – 14 000][3400 – 14 000]

South & South-East Asia

170 000170 000 [70 000 – 380 000][70 000 – 380 000]

Oceania30003000

[830 – 7900][830 – 7900]

North America11 00011 000

[3500 – 27 000][3500 – 27 000]

Caribbean22 00022 000

[9800 – 43 000][9800 – 43 000]

Latin America32 00032 000

[19 000 – 59 000][19 000 – 59 000]

East Asia 64006400

[2000 – 16 000][2000 – 16 000]

Total- 2.3 millionSub-Saharan Africa-2 million

UNAIDS (2006)

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Estimated Number of Children < 15 years

Newly Infected with HIV in 2005Western &

Central Europe200200[<400][<400]

North Africa & Middle East69006900

[3200 – 12 000][3200 – 12 000]

Sub-Saharan Africa470 000

[370 000 – 590 000]

Eastern Europe & Central Asia

2300 2300 [1400 – 3900][1400 – 3900]

South & South-East Asia

44 00044 000 [ 23 000 – 75 000][ 23 000 – 75 000]

Oceania11001100

[400 – 2800][400 – 2800]

North America500500

[<1000][<1000]

Caribbean37003700

[2100 – 5800][2100 – 5800]

Latin America50005000

[3500 – 8000][3500 – 8000]

East Asia 23002300

[1000 – 4100][1000 – 4100]

Total-540,000Sub-Saharan Africa-470,000

UNAIDS (2006)

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Estimated Number of Pediatric Deaths

Attributed to HIV/AIDS in 2005Western &

Central Europe<100<100[<200][<200]

North Africa & Middle East49004900

[2000 – 9500][2000 – 9500]

Sub-Saharan Africa330 000330 000

[250 000 – 440 000][250 000 – 440 000]

Eastern Europe & Central Asia

1200 1200 [620 – 2300][620 – 2300]

South & South-East Asia

29 00029 000 [14 000 – 54 000][14 000 – 54 000]

Oceania600600

[200 – 1800][200 – 1800]

North America<100<100[<200][<200]

Caribbean31003100

[1600 – 5100][1600 – 5100]

Latin America29002900

[1800 – 4900][1800 – 4900]

East Asia 14001400

[530 – 2700][530 – 2700]

UNAIDS (2006)

Total- 380,000

Sub-Saharan Africa-330,000

What is happening to HIV-infected children in Ethiopia?

Current National Status-2009

Estimated number of people living with HIV (PLHIV) in 2009 : 1,116,216 →41 % males and 59 % females (1:1.5)

Of which, 72,945 (6.6%) are children (<15 years) 131,145 new infections estimated to occur in

2009 58,290 deaths occurred due to AIDS in 2008. Total AIDS Orphans (2009): 855,720 Total ART Need in 2009: 336,160 (20,522

children) Up to April ,2009 0nly 10,077 children were on

ART out of 20,522 who are in need of it.

HIV Population Size by Sex and Age – Ethiopia 2005

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Pediatric HIV care and treatment in Ethiopia

Pediatric Access to Chronic HIV/Care & ART

561

3939

6568

199

1922

3071

0

1000

2000

3000

4000

5000

6000

7000

2005 2006 2007

Ever Enrolled Ever Started ART

• Over 66,000 people are receiving ART in Ethiopia, 2007

• However, only 4.7% (3144) are children

• Only 7.2% (3144) of the 43,000 eligible children were on ART as of May 2007

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FMOH 2007

Why are so few children in need getting care and treatment?

Technical barriers

Developmental challenges in pediatrics

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BARRIERS TO CARE: Technical• Diagnostic challenges

• Identification of exposed infants,, virologic testing of infants <18 months, stigma, consent, etc)

• Relative failure of effective PMTCT• Low PMTCT up take and follow up

• Infrastructure & human resource requirements• Challenge of transforming health systems accustomed to

acute, episodic care into systems capable of providing chronic care

• Human resource requirements• Human resource training• High staff turnover• Lack of pediatric comfort amongst providers14

BARRIERS TO CARE: Developmental Challenges• Children are not small adults

• Different mode of transmission > 90% from MTCT• Growth and development• Immature immune system• Dependent on care giver

• HIV and children• Immature immune system + high viral load → rapid disease

progression • High morbidity and mortality

• Half will be dead by 2 years and ¾ will be dead by 5 years of age if they are not provided with HAART

• Complexity of ART administration• Lack of palatable pediatric formulations • Weight-based dosing• Dependence on family for medication supervision

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Children with HIV Do Well on Treatment

• Dramatic improvements in morbidity and mortality have been seen in high-resource settings secondary to: – Early infant diagnosis

– Accessible pediatric health services– Widespread use of OI prophylaxis (cotrimoxazole)– Widespread use of HAART– Successful perinatal prevention

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Children in Low resource settings also Do Well on

HAART

0

5

10

15

20

25

-2 6 12 18 24

CD4%

HARRT Initiation

Time on HAART (months)

CD

4+

Per

cen

t

Modified from Fassinou et al., AIDS, 2004

How do we overcome these barriers?• Expand and strengthen entry point for pediatric service• Establish strong linkage between PMTCT & ART

service • Family centered approach • Under 5 clinics – opt out approach • Effective linkage with orphanage & community• Service decentralization and roll out

• Expand early infant diagnosis (use of DBS /PCR)• Enhance case finding and referral• Link PMTCT to infant follow-up• Ensure follow-up and comprehensive care for exposed

infants18

How do we overcome these barriers?

• Effective PMTCT • Engage mothers and their families in comprehensive

care and treatment• Point of service testing for pregnant women in the ANC,

MCH, labor and delivery and postnatal clinics• Provide HAART for eligible mothers and effective

prophylaxis for mothers who are not eligible

• Pediatric Care and Treatment • Provide minimum standard of care for all HIV-infected

children• Provision of HAART for all eligible children• Family support and psychosocial support• Increase availability of and access to pediatric ART

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Conclusion• Pediatric HIV care and treatment can be implemented

in resource limited setting

• Children have unique needs and can be challenging but not impossible

• Early diagnosis and prompt treatment will improve survival

• PMTCT is the way to safeguard children's health and prevent further infections in children

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ADD SOMETHING TO THE CHILD!!!!!!!!

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Questions?

Factors that predict rapid disease progression

• Maternal factors• Low CD4• High viral load (in pregnancy)• Advanced clinical disease• Low vitamin A levels (in pregnancy)• Maternal death

Factors that predict rapid disease progression

• Infant factors• Early acquisition of HIV• High viral load• Early CD4 depletion • Early onset of HIV-related symptoms

• growth delay• neurodevelopmental delay• hepato-splenomegaly • lymphadenopathy

Clinical Staging of Pediatric HIV/AIDS

• Old WHO clinical stages:• Three stages• Didn’t capture many disease manifestations• Didn’t include measures of immunologic

status

• New WHO clinical staging: • Four clinical disease categories;

asymptomatic, mild, advance and severe • Expanded comprehensive list of associated

conditions based on prognosis• Standardized criteria for presumptive and

definitive diagnosis 25

WHO Staging for <15 Years Old

Clinical Stage 1 (Asymptomatic)Asymptomatic

PGL

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WHO Staging for <15 Years Old

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Clinical Stage 2 (Mild)Hepatosplenomeagly

Papular pruritic eruptions, Extensive wart virus infection

Extensive molluscum contagiousum Fungal nail infections,

Recurrent oral ulcerationsLinear gingival erythema (LGE)

Angular cheilitis Parotid enlargement

Herpes zoster Recurrent or Chronic URTI (otitis media, otorrhea,

sinusitis)

WHO staging for <15 Years Old

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Clinical Stage 3 (Advanced)Moderate unexplained malnutrition not adequately responding to

standard therapy Unexplained persistent diarrhea (14 days or more)

Unexplained persistent fever (intermittent or constant for longer than one month)

Oral Candidiasis (outside neonatal period), Oral hairy leucoplakia

Acute necrotizing ulcerative gingivitis/periodontitisPulmonary TB

Severe recurrent bacterial pneumoniaUnexplained anemia (<8mg/dl),and/or neutropenia (<500/mm3) and/or

thrombocytopenia, (<50,000/mm3) for >1 month

Chronic HIV associated lung disease including bronchiectasisSymptomatic lymphoid interstitial pneumonitis (LIP)

WHO staging for <15 Years Old

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Clinical Stage 4 (Severe)

Unexplained severe wasting or severe malnutrition not adequately responding to standard therapy

Pneumocystis pneumonia Recurrent severe bacterial infections (empyema, pyomyositis, bone or joint infection, meningitis, but

excluding pneumonia) Chronic herpes simplex infection (orolabial or cutanoeus >

1 month, visceral of any duration)Kaposi’s sarcoma, esophageal candidiasis, CNS

toxoplasmosis, HIV encephalopathy

WHO Staging for <15 Years Old (Stage 4 continued)

CMV infection (retinitis or infection of organs other than liver, spleen or lymph nodes; onset at the age of 1 month or

more)Extrapulmonary cryptococcosis including meningitis

Any disseminated mycosis (e.g. extrapulmonary histoplasmmosis, coccidiomycosis, penicillosis)

Cryptosporidiosis, isosporiasisDisseminated non-tuberculous mycobacteria infection

Candida of the trachea, bronchi or lungsAcquired HIV associated rectal fistula, cerebral or B-cell

lymphomaProgressive multifocal leucoencephalopathy (PML)HIV associated cardiomyopathy or HIV associated

nephropathy30

WHO Classification of Immunodeficiency in Infants and Children

Age related CD4 values

Immunological Classification

<12 months (CD4 %)

12-35 months (CD4 %)

36-59 months (CD4 %)

> 5 years(CD4

cells/mm3)

Not significant > 35% > 30% > 25% > 500

Mild 30-35% 25-30% 20-25% 350-499

Advanced 25-30% 20-25% 15-20% 200-349

Severe < 25% < 20% < 15% < 200 or 15%

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Components of Routine Care for the HIV-Infected Child

1. History (past, interim, parental concerns)

2. Nutrition evaluation3. Developmental assessment 4. Physical examination5. Laboratory evaluation6. Staging/classification7. Preventing Opportunistic infections8. ARV eligibility9. Assessment & plan10.Follow up schedule

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1. History

• Why is history important?• Develop clinical profile for older children

entering the program• Identify changes in health status since last visit • Identify changes in home setting that may

affect child’s health• PAST HISTORY

• Newly enrolled older children • HIV-related illnesses• Hospitalizations• Medications (ARV, OI prophylaxis, PMTCT)

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1. History (2)

Interim History• New health problems

• Signs & symptoms checklist• HIV-related illness

• Current Medications• antiTB medications• Medications for OI prophylaxis e.g.

Cotrimoxazole• Other alternative medications (herbal

preparations)

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2. Nutritional Evaluation

At every visit:

• Nutrition and feeding history – exclusive breastfeeding or formula feeding?

• Weigh, measure height/length and HC and examine child

• Use growth curves to monitor growth pattern.

Any child who is not thriving needs extensive nutritional history.

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Failure-to-Thrive

• The failure to sustain a normal velocity of weight and/or height growth during the first 3 years of life – downward crossing of 2 percentiles over time..

• Can be quantified using growth curves.• May be indication:

Of HIV disease in exposed infantFor ARV treatment in infected infant/childOf ARV treatment failure in child on therapy

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3. Developmental Assessment

• At every visit • Ask about the infant’s development• Simple questions should focus on four critical

developmental domains; cognitive, motor, language, and social

• This can be done through observation during the physical exam or asking the parent

• The developmental checklist may be helpful• Ask about school performance for school aged kids• Delayed acquisition of developmental milestones or

loss of previously acquired skills can be the first sign of HIV encephalopathy

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3.Developmental Assessment (2)

• Developmental Checklist• 1 month: raises head,

crawling movement, alerts to sound

• 2 months: head midline, lifts chest off table, smiles socially

• 4 months: rolls front to back, laughs

• 6 months: sits unsupported, babbles

• 9 months: pulls to stand, says “mama”

• 12 months: walks alone, two words

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Red Flags!AGE WARNING SIGNS

1 monthDoes not regard face, no eye contact, no smile, poor suck, floppy

2 months Does not look at you with both eyes at least for a few moments, and does not follow with eyes if you move your face slowly from side to side

3months Does not respond to sound by quieting

4months Does not hold head steady for a few moments when you sit him up, does not grasp rattle that you put into his palm

5months Does not raise head and support weight on arms when in prone position

6 months Cannot reach for objects with both hands, Floppy, no response to sound, Poor social response to people

9 months Unable to sit unsupported , hand preference, fisting, persistence of primitive reflexes

12months Unable to bear weight on legs

15 months Does not walk alone, is not using at least one word meaningfully

18 months Does not use at least 3 words, and does not point to what he wants

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4. Physical Examination

• Perform careful physical examination at every visit

• Initial exam should be comprehensive including examination of all organ systems• Identify any HIV related physical findings;

thrush, lymphadenopathy, organomegaly,dermatitis, encephalopathy etc

• Subsequent exams can be guided by findings on the symptom/sign checklist

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5. Laboratory Evaluation

• Which Laboratory Tests Need To Be Done? • Complete Blood Count with DC• CXR if clinically indicated • Pregnancy test for sexually active adolescent

females• CD4 number and percent

When infant is determined to be HIV-infectedUpon enrollment for older childrenEvery six months there after

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Why use CD4 percentage in Children?

• CD4 counts and percentages in healthy infants are very high at birth and during the first year of life and then decline .

• The absolute CD4 count varies a lot during the first year of life and is more than 3 times that of adults

• CD4% is a more stable value than absolute number, so percentage is preferred in children under 5 years of age

• Because of these differences, adult values do not apply in children below the age 5 years• CD4 count of 500 is considered okay for a 7 year old but is

severe suppression for a 6 month old

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Calculating the CD4 Percentage

• Calculate the CD4 percentage for a 13 month old HIV-infected infant• CD4 absolute is 640mm3

• WBC is 10,000mm3

• N-38%, L 48%, M-12%, E-2%• Calculate the TLC = 10,000 x .48 = 4800• The CD4 percentage= 640 X 100 = 13% 4800

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7. Preventing Opportunistic Infections

• Occurs with severe immune suppression• Young children have primary infection

rather than reactivation as in adults• Immature immune system of the infant

leads to more fulminant course than in adults

• Prophylaxis prevents disease progression and morbidity and mortality!

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Cotrimoxazole Prophylactic Therapy

• Cotrimoxazole Prophylactic Therapy (CPT) is one of the most important interventions for HIV-exposed infants and HIV-infected infants and children

• It prevents • Pneumocystis jiroveci (formerly Pneumocystis carinii), most

common opportunistic infections in infants and young children, with a very high mortality rate

• Prevents diarrheal infections • Prevents malaria

• Without prophylaxis, 40% of infants and children with AIDS experience PCP

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CTX decreases mortality and hospitalizations- The CHAP Trial

• A randomized placebo-controlled trial of 541 children in Zambia showed that the use of CTX

• Decreased mortality by 43 %

• Decreased hospitalizations by 23 %

• Did not increase adverse drug effects

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Chintu et al, Lancet 2004

Which HIV-infected children should get Cotrimoxazole Prophylactic Therapy?

• All HIV-infected infants < 12 months • All HIV-infected children 1- 4 years with:

• Clinical stage 2, 3 or 4 disease or • CD4 < 25 %

• All HIV-infected children > 5 years with:• Clinical stage 2, 3 or 4 disease or• CD4 < 350

• All HIV-infected infants and children with prior Pneumocystis pneumonia

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Dosing Recommendations for Cotrimoxazole

• Cotrimoxazole suspension• Use weight band chart for

dosing • Administer once daily

• Toxicities are rare in children and include • Rash• Fever• Bone marrow suppression

(neutropenia)

• Use Dapsone (2mg/kg/day, max 100mg) for severe allergy to cotrimoxazole

Trimethoprim/sulfamethoxazoleCTX/SMZ, Cotrimoxazole, Septrim®, Bactrim®

Age

Suspension

40mg TMP/200mg SMZ per 5ml

Single-Strength Tablet

80mgTMP/400mg SMZ

< 6 months 2.5 ml daily

¼ tablet

6 months - 5 years

5 ml daily ½ tab daily

6 - 14 years 10 ml daily 1 tab daily

> 14yrs 2 single-strength or one double-strength

tab daily

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Tuberculosis Screening

• TB is the most common opportunistic infection among HIV-infected patients in Africa, SE Asia

• Leading cause of AIDS-related deaths worldwide: 1/3 of all AIDS-related deaths are due to TB

• High rates of co-infection (HIV and TB)• Zambia: 69% hospitalized with clinical TB test HIV+• Cote d’Ivoire: 23.4% • Johannesburg: 42%

• Can be prevented by:• Treatment of latent TB infection (INH preventive therapy-

IPT)• Use of antiretroviral therapy

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Tuberculosis Screening: Special Issues for Children

• TB is difficult to diagnose in children• Limited yield of diagnostic procedures:

• Poor sputum production• Low yield of gastric aspiration• Sputum induction and bronchoscopy not routinely

used• Multiple varied clinical manifestations• Overlap with other HIV disease manifestations• BCG vaccination results in false positive Tuberculin Skin

Testing (TST)• Limited sensitivity of TST in HIV-infected children

• Higher risk of progression from latent to TB disease compared with adults – 50% progression in those less than 1 year old.

• Associated with severe complications• Meningitis• Miliary TB

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TB screening in children

Symptom based screening• Cough > two weeks • Fever >two weeks( fever of > 38oC)

after exclusion of common causes like malaria and pneumonia

• Documented weight loss or failure to gain weight

• Close contact with active TB case51

Positive Screening: one or more symptoms

Exclude active TB as per local and national Guidelines• Lack of response to common illnesses in sick children

Laboratory investigations • Sputum for AFB in children above five

years of age• Gastric aspirate in children below five

years of age• Radiologic examination• Mantoux test if available

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Who should take INH preventive therapy• Because of limited resources only children

at high risk of disease progression shall receive preventive therapy.• All children below the age of 5 years exposed to

adults with active pulmonary TB (smear positive, open TB) regardless of HIV status,

• All HIV infected children age > 5 years regardless of history of exposure as at this is there may unwittnessed exposure

and have no symptoms and signs of active TB

disease.• Dose of INH

• 5 – 10mg/kg p.o for 6 months• Children with active disease shall receive standard therapy

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8. ARV Eligibility

WHO Recommendations for Initiating ART • Children with WHO Stage 3&4• Children with WHO Stages 1 and 2 should

only initiate ART if they have severe immune suppression (CD4 percentage/count below age threshold)

• HIV exposed infants < 12 months of age who test HIV positive by DNA PCR

• Infants and children < 18 months fulfilling the clinical criteria for presumptive dx of severe HIV disease in the absence of virologic test. 54

Presumptive dx of severe HIV disease criteria•HIV exposed/ antibody positive

•< 18 months of age•Symptomatic with at least two of:

•Oral thrush•Severe pneumonia•Severe wasting/malnutrition•Severe sepsis

•Recent HIV-related maternal death, advanced HIV disease in the mother, and/or CD4<25% will also support this diagnosis

•It is important to confirm the diagnosis as soon as possible.

Prior to ART Initiation-Clinical Evaluation

• Confirm HIV Diagnosis and Eligibility

• Laboratory confirmation as soon as possible• WHO Clinical and Immunological Staging

Criteria• Baseline growth measurements

• Height and weight on all children• Head circumference for children < 2 years of

age• Baseline neurodevelopmental status• Screen for and treat any inter-current or opportunistic

infection• Ensure access to nutrition and prophylaxis 56

Prior to ARV Initiation – Laboratory Evaluation

• CD4 count • Full blood count• Liver function test: Alanine transaminase• Kidney function: Serum creatinine• TB screening

• History• Mantoux test and Chest x-ray if available

• When indicated: syphilis serology, Hepatitis B virus screening, pregnancy test

• When available: viral load57

Prior to ART Initiation-Adherence Preparation

• Identify and fully counsel care givers• Confirm availability of support services

(family, social, inpatients care etc)• Consistent caregiver for administration,

supervision of medication

• Identify barriers to treatment for the care taker and address where possible

• Prepare family and child for adherence • Completion of adherence/counseling sessions

– may vary at each site

• Address disclosure where appropriate58

Medical Contraindications to ARV drugs• Severe Anemia (Hb<6.9 gdl) Contraindication to AZT,

replace with d4T • Severe Neutropenia (ANC<250 mm3) AZT use requires

close monitoring. Can substitute d4T if ANC falls• Severe Renal Insufficiency (Creatinine > 3 times

normal) Contraindication to ARV use. Patient not eligible for ART

• Severe Hepatic Insufficiency (LFTs > 5 times normal) Contraindication to NVP use. Use EFV in children older than 3, PI treatment suggested for small children

• History of prior ARV use Potential for ARV resistance. Consult for expert management

• Current use of rifampin containing TB regimen- Interactions with NVP. If CD4 is high, consider deferring ART or use ritonavir containing regimen for children under 3 and EFV containing regimen for children older than 3

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Pediatric First-Line Regimens in Ethiopia

*LPV/r for infants exposed to NVP due to {PMTCT*

Children less than 3 years of age:(ZDV or d4T) + 3TC + NVP *

Children older than 3 years of age:(ZDV or d4T) + 3TC + NVP

or(ZDV or d4T) + 3TC + EFV

Special CircumstancesWHO recommends Triple NRTI

• (AZT+3TC+ABC or d4T + 3TC +ABC)

as alternative option for initial therapy under certain circumstances:• Infants and children < 3 years of age receiving

TB treatment where NVP or PI cannot be used because of interactions with rifampicin

• Pregnant adolescent with CD4 cell > 250/mm3 in which both NVP and EFV are contraindicated and PI based regimes are not available

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9. Assessment & Plan

• Synthesize components of evaluation• Diagnose and manage complications• Order laboratory studies• Refer for counseling/support groups• Follow-up appointment

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10. Follow-up Schedule for the HIV-Infected Child?• Infants and children below the age of 2 years

monthly• Asymptomatic children > 2 years not on ART

every three months• Asymptomatic children > 2 years on ART monthly for adherence assessment and prescription

refill every 3 months for clinical evaluation

• Symptomatic children > 2 years monthly and as often as necessary under certain

circumstances.• At initiation of ART infants and children every two weeks for two visits and then every month

until clinically stable (6month).63

Summary

• Early diagnosis is critical for survival• Systems for following children need

to be established in the clinical setting

• Prophylactic therapies and nutritional support are critical interventions to decrease HIV morbidity

Questions?