Medical students lecture on paediatric HIV

1. PAEDIATRIC HIV/AIDS

2. OUTLINE
• INTRODUCTION
• EPIDEMIOLOGY
• BIOLOGICAL STRUCTURE
• MOLECULAR EPIDEMIL0GY
• PATHOGENESIS
• NATURAL HISTORY
• RISK OF PROGRESSION
• TRANSMISSION
• CLINICAL MANIFESTATIONS
• STAGING OF DISEASE
• LABORATORY DIAGNOSIS
• THERAPY
• CLASSES OF DRUGS USED
• PREVENTION
• FOLLOW UP

3. INTRODUCTION
• HIV and AIDS is a major cause of infant and childhood morbidity
and mortality in Africa
• In children <5 years it accounts for 7.7% of mortality worldwide
• In 2007, AIDS accounted for a rise of >19% of infant and a 36% rise
in under 5 mortality rates
• The high burden of paediatric HIV disease in Africa is due to:
– high birth rate
– high rates of mother-to-child transmission
• The fast rate of progression of HIV infection in children is partly
responsible for high morbidity and mortality

4. EPIDEMIOLOGY
• HIV infection, first identified in 1981 and first case in Nigeria was in 1986
• According to UNAIDS, in 2017, 1.8million children <15years were living
with HIV globally
• Children less than 15years account for:
– 5% of Persons Living with HIV/AIDS (PLWHA)
– 10% of new infections and 9% of AIDS related death.
– With introduction of ARVs, survival of paediatric
patients has largely increased.
• In 2017, up to 940,000 children < 15years received ART showing an increase
from 640,000 in 2012.

5. EPIDEMIOLOGY
• The World Health organisation (WHO)
estimation in 2013 stated that
–32million children younger than 15yrs of
age worldwide were living with HIV-1
infection,
–90% were from sub-Saharan Africa.
In the same year, about 199,000 children
were newly infected

6. EPIDEMIOLOGY
• In Africa, almost 90
• the prevalence of HIV infection in children aged
0-14years ranges from
• 500 children in Tunisia,
• 220,000 children in Nigeria
• to 280,000 children in South Africa.
• Newly infected children ranges from 100 children
in Egypt, Algeria, Morocco and Mauritania to
36,000 children in Nigeria

7. EPIDEMIOLOGY
National HIV prevalence has increased exponentially from 1.8% in
1991 peaking at 5.8% in 2001 and progressively declining since then to
the current figure of 3.1% in 2014 (ANC Survey Report).
• Nigeria has the second highest burden of HIV globally with 3.4
million PLHIV as at 2014.
• Over 2 million Nigerian children are AIDS ORPHANS
• In 2019, The state to state variation in HIV prevalence in the country
ranged from 0.3% in Katsina State to 5.5% in Akwa Ibom state
• Based on geopolitical zone:
• SS 3.1% NC 2.1%
• SE 1.9% SW 1.2%
• NE 1.1% NW 0.6%

8. HIV infection is acquired in children through:
• Mother-to-child (or vertical) route
– Accounts for >90% of transmission in children
– Can occur in-utero(5-10%), at delivery(5-20%) or during
breastfeeding
– Prolonged breastfeeding and mixed feeding are key factors
responsible for higher transmission rates in Africa
– Without intervention overall transmission rate is 15-45%.
• Sexual contact – forced or consensual
• Blood and blood product transfusion
• Use of contaminated sharps for scarification, tattoos, and
surgical procedures
Modes of HIV Transmission

9. In Nigeria, it was estimated that ONE
SERO-EXPOSED INFANT is born every
5 minutes but this is declining with
universal ARVs for pregnant women

10. • The Lenti-virus group of Retroviruses
• Retroviruses contain reverse transcriptase enzyme used
for synthesis of pro-viral DNA from viral RNA
• The mature genome of HIV is diploid with 2 identical
positive sense single-stranded RNA copies
• The envelope is made of 2 glycoproteins:
– Gp120 and Gp41 for HIV-1
– Gp105 and Gp36 for HIV-2.
• Antibodies to these 2 sets of proteins do not usually
cross react – this differentiates serologic responses of
HIV-1 and HIV-2.
Biology and Structure of HIV

11. Biology and Structure of HIV cont…
• Has an outer double lipid
membrane (envelope) lined by
matrix protein (p17)
• Surface glycoprotein gp120
and trans-membrane gp41
• The gp spikes surround the
cone-shaped protein core
(p24)
• Core protein contains genetic
material (RNA) and enzymes.

12. Viral enzymes
• Reverse Transcriptase (RT),
converts viral RNA into a
double stranded (DNA)
• Integrase cause integration
of double stranded DNA
into host’s DNA
• Protease splits generated
macro-proteins into smaller
viral proteins which get
incorporated into new viral
particles.
Biology and Structure of HIV cont…

13. There are two types of HIV:
• HIV-1
– Main cause of the worldwide pandemic
• HIV-2
– Mainly found in West Africa, Mozambique and
Angola
– Causes a similar but less severe illness to HIV-1
– Less efficient transmission, rarely cause MTCT
– Less aggressive with slower disease progression.
Molecular Epidemiology of HIV

14. • HIV-1 Subtype A is commonly found in Central,
West and East Africa
• HIV-1 Subtype B:
– Prevalent in Western Europe and North America
– Most knowledge about HIV-1 was from studies of
subtype B.
• All HIV-1 subtypes have been found in Africa
• Recombinant forms of HIV exist
• A/G recombinant is most predominant in West
Africa.
Molecular Epidemiology of HIV….cont….

15. HIV is a retrovirus with a simple cellular structure made
of: Two important membrane glycoproteins responsible for its
antigenic identity:
− HIV-1 (Gp 120 and Gp 41)
− HIV-2 (Gp 105 and Gp36).
− Three important enzymes responsible for entry into
host cell, incorporation of its RNA into host DNA,
replication and assembly of new viral particles
− Reverse transcriptase
− Integrase
− Protease.
SUMMARY OF MOLECULAR EPIDEMIOLOGY OF HIV

16. • HIV-1 primarily targets CD4+ molecule on T-helper
• Other target cells include macrophages and glial cells
• The virus uses its gp120 and gp41 to bind to CD4+ receptors
and chemokine co-receptors (CCR5 & CXCR4)on the host
cell membrane
• This permits entry of contents of the viral particle into host
cell cytoplasm
• The viral enzymes and RNA are then released to begin the
process of replication while the viral envelope is shed.
PATHOGENESIS

17. • HIV RNA is transcribed by reverse transcriptase to a
double stranded DNA
• It is then integrated into host DNA by integrase and
continues to reside there indefinitely as a provirus
• On activation, the proviral DNA is transcribed into
mRNA by host enzyme RNA polymerase to begin
replication
• The mRNA is then translated into viral proteins which
assemble and “bud-off” from the host cell membrane.
PATHOGENESIS cont….

18. PATHOGENESIS cont….
• CD4+ cells play vital roles in humoral and cell-mediated
immunity such as:
– Maturation of B-cells to plasma cells to make antibodies
– Induction of natural killer (NK) cells to destroy tumour cells
– Activation of macrophages for efficient phagocytosis
– Suppression of other T and B-cells by CD8+ suppressor T-cells
– Lysis of infected cells by cytotoxic CD8+ T-cells.
• Continuous CD4+ loss lead to progressive immunosuppression
and increase the incidence of opportunistic infections(Ois).

19. PATHOGENESIS cont….
• Reduced activity of NK cells leads to increased incidence of
tumours
• Continuous viral replication leads to progressive CD4+ cell
destruction which in turn results in:
– More CD4+ cell production
– Continuous infection of surviving CD4+ cells
• CD4+ cells become eventually overwhelmed and the immune
system fails to cope with opportunistic infections, leading to
progression to AIDS.

20. KEY POINTS OF PATHOLOGY
• HIV-1 targets CD4+ receptor and chemokine co-
receptors on T-helper lymphocytes to gain entry into
human host cells
• Destruction of CD4+ cells causes progressive
immunosuppression and increased incidence of OIs
• The CD4+ cells are eventually overwhelmed and the
immune system fails, leading to disease progression
to AIDS.

21. NATURAL HISTORY OF HIV
Adults and Children older than 5 years
• A typical HIV infection can be divided into three stages: primary infection,
asymptomatic infection, and symptomatic infection including AIDS.
• Following primary HIV infection, the CD4+ cell count decreases and the
HIV RNA rises significantly.
• With sufficient exposure to viral antigens, cytotoxic T-lymphocyte
responses are generated and the HIV viral load typically declines to an
equilibrium known as a virologic “set-point,” within 6 to 12 months of
infection.
• Once this viral set-point is reached, the CD4+ cell count may rebound
again marginally, although it does not often return to baseline values.
• Concurrent with these events are clinical manifestations of acute HIV
infection in 30% to 60% of individuals.

22. NATURAL HISTORY OF HIV contd
• Absolute CD4+ count varies with age and is generally higher
in healthy younger children
• CD4+ counts slowly decline to adult levels by 6 years
• CD4+% does not change with age; thus it is the preferred
parameter for monitoring disease progression in children
≤5 years
• Risk of AIDS or death rises as CD4+% falls to <25 in infants,
to <20 from 1-3 years and to <15 thereafter
• Disease progression is faster and prognosis is poorer in
infants than in older children.

23. Natural History of HIV cont …..
• Viral Load(VL) trends in perinatally infected infants
differs from that in adults and children >5 years:
• In Infants:
– VL levels are low at birth
– Increases to levels >100,000 to millions of copies/ml
by 2 months of age
– Remain at same level throughout first year of life
– Decline slowly over the next few years to a “set point”.

24. Viral Load and T-lymphocytes Dynamics
in HIV Infected Adults and Children

25. There are 3 categories of disease progression:
Category 1 (25 – 30%):
• Disease acquired in-utero or perinatally
• Rapid disease progression and death within 1st year of
life.
Category 2 (50 – 60%):
• Develop symptoms early in life
• Deteriorate and die by 3 to 5 years.
Category 3 (5 – 25%):
• Long-term survivors: may live beyond 8 years of
age.
HIV Disease Progression in African Children

26. • Infant factors:
– Infecting viral dose
(maternal VL)
– Infection before 4
months of life
– Infant peak viraemia
– Rapid decline in CD4+
– Clinical AIDS
– p24 antigenaemia.
• Maternal factors:
– VL at time of delivery
– CD4+ count (<200)
– Rapidly progressive
disease
– Maternal death.
Factors Predicting Disease Progression

27. MATERNAL RISK FACORS
• High VL
• STI
• New infection in
pregnancy
• Advanced disease
• APH
• PROM
• Prolonged labour
• Invasive delivery
procedures
• Instrumental
deliveries eg forceps,
vacuum
• Episiotomies/genital
lacerations
• Breast conditions

28. Fetal risk factors
• Oral lesions in breast feeding infant
• Mixed infant feeding
• Prematurity
• First of twins delivered per vaginam

29. CLINICAL
MANIFESTATIONS

30. • Although clinical features are used to make diagnosis
of HIV infection, very often they overlap with
features of other diseases.
• The clinical manifestations of HIV disease in
children include:
• Fever
• Persistent generalized lymphadenopathy
• Respiratory illnesses: pneumonias, pharyngo-
tonsillitis, otitis media, mastoiditis
• Malnutrition
• Gastrointestinal conditions: diarrhoea, vomiting,
parotid enlargement.

31. • SOME CLINICAL MANIFESTATIONS ARE VERY
SPECIFIC TO HIV INFECTION EG:

32. • Pneumocystis pneumonia
• Oesophageal candidiasis
• Extra-pulmonary cryptococcosis
• Invasive salmonella infection (especially non-typhoidal)
• Herpes Zoster (shingles) dermatomal
• Kaposi’s Sarcoma
• Lymphoma
• Progressive multifocal leuco-encephalopathy.
• Lymphoid interstitial pneumonitis

33. MANIFESTATIONS COMMON IN HIV
INFECTED CHILDREN BUT NOT
COMMON IN UN-INFECTED CHILDREN

34. • Severe/recurrent bacterial infections
• Persistent or recurrent oral thrush
• Bilateral painless parotid enlargement
• Persistent generalized lymphadenopathy - PGL (non-
inguinal)
• Hepato-splenomegaly (in non-malaria area)
• Persistent &/or recurrent fever
• Neuro-developmental dysfunction
• Herpes Zoster, single dermatome
• Persistent generalized dermatitis unresponsive to
treatment.

35. • FEATURES COMMON IN BOTH
INFECTED AND UN-INFECTED
CHILDREN

36. • Chronic recurrent otitis media with ear discharge
• Persistent or recurrent diarrhoea
• Severe pneumonia
• Tuberculosis
• Bronchiectasis
• Failure to thrive
• Marasmus.
National Paediatric ART Training Slides Unit 3 14

37. Classification of HIV-associated
Clinical Disease
WHO Clinical
Stage
Asymptomatic 1
Mild 2
Advanced 3
Severe 4
WHO staging for HIV infection and
disease in infants, children and adolescents

38. IMMUNUNOLOGICAL CLASSIFICATION FOR HIV INFECTED CHILDREN
Immunological
category
CD4 count (cells/μL)
No evidence of
Immunosuppression
≥500
Evidence of
Immunosuppression
200-499
Severe
Immunosuppression
<200

39. WHO CLINICAL stage 1
• Asymptomatic
• Persistent generalized lymphadenopathy.

40. WHO CLINICAL stage 11(Mild disease)
• Unexplained persistent hepatosplenomegaly
• Papular pruritic eruptions
• Extensive wart virus infection
• Extensive molluscum contagiosum
• Recurrent oral ulcerations
• Unexplained persistent parotid enlargement
• Linear gingival erythema
• Herpes zoster
• Recurrent/chronic upper respiratory infection (otitis
media, sinusitis, tonsillitis)
• Fungal nail infections.

41. WHO CLINICAL stage 111(Advanced Disease)
• Moderate malnutrition unresponsive to standard
therapy
• Persistent diarrhoea (≥14 days)
• Persistent fever (>37.5 oC, intermittent or
constant, exceeding 1 month
• Persistent oral candidiasis (after 6 weeks of age)
• Oral hairy leukoplakia
• Necrotizing ulcerative gingivitis/peri-odontitis.

42. WHO CLINICAL stage 111(Advanced Disease) contd
• Lymph node TB
• Pulmonary TB
• Severe recurrent bacterial pneumonia
• Lymphoid interstitial pneumonia
• Chronic HIV-associated lung disease e.g.
bronchiectasis
• Hb level of <8g/dl
• Neutrophil count of <0.5 x 109/L
• Platelets count of <50 x 109/L.

43. WHO CLINICAL stage 1V( Very Severe
Disease)
• Severe malnutrition not responsive to therapy
• Pneumocystis pneumonia
• Recurrent/severe bacterial infection (excluding pneumonia) e.g.
– Empyema
– Pyomyositis
– Bone/joint infections
– Meningitis.
• Chronic herpes simplex infection (for >1 month)
• Extra-pulmonary TB.

44. WHO CLINICAL stage 1V(Severe
Disease) contd…
• Kaposi sarcoma
• Candidiasis (oesophageal, tracheo-bronchial or pulmonary
• CNS Toxoplasmosis after neonatal age
• HIV encephalopathy
• CMV retinitis or infection of other organs after neonatal age
• Extra-pulmonary cryptococcosis.

46. WHO CLINICAL stage 1V(Severe
Disease) contd…
• Disseminated fungal infections
– Histoplasmosis
– Coccidiodomycosis.
• Chronic cryptococcosis
• Disseminated atypical mycobacterial infection
• Cerebral B cell Non-Hodgkins lymphoma
• Progressive multifocal leukoencephalopathy
• HIV-associated cardiomyopathy.

48. DIAGNOSIS
• Diagnosis may be:
– Clinical - based on signs and symptoms, or
– Clinical supported by laboratory findings.
• HIV and AIDS should be suspected in
children with suggestive clinical features
or HIV-associated conditions.

49. • All HIV-exposed infants, the sexually assaulted and
those exposed to potentially infectious body fluids
should be evaluated
• PITC
• If infection is confirmed, clinical disease staging
should be determined using the WHO staging system.

50. LABORATORY DIAGNOSIS
• There are 2 broad categories of tests: Antibody and
virology
• ANTIBODY detection (reliable in children above 18 months of
age)
− HIV Rapid test: (DRT) simple and easy to perform
− ELISA: needs more equipment, time, technical skills.
− Western blot: gold standard but expensive and produce
indeterminate results.

51. VIROLOGY TESTS
• Most useful in children
− DNA PCR DBS sample
− RNA PCR (plasma viral load): monitors disease progression and
response to treatment
− P24 Ag: Very specific for detection of core Ag during early stage of
infection (window period); negative result does not rule out
infection
− Viral cultures: highly sensitive, very specific but time consuming,
expensive. Only used for research purposes

54. • Antibody tests are unreliable for HIV
diagnosis in children <18 months, but
DNA-PCR is diagnostic
• All exposed babies who are
breastfeeding should get 2 DNA PCR
tests
− If initial DNA-PCR is negative,
testing should be repeated 12
weeks after cessation of
breastfeeding

55. • irrespective of method of
feeding
• Antibody tests are reliable for
children >18 months except
during window period, thus
repeat test after 3 months
• DNA/RNA PCR could be used to
resolve doubtful results

56. THERAPY
• ANTI RETROVIRAL THERAPY(ART) IS LIFE-LONG
• The major goals of ART in children are to:
− Stop and reverse progression of disease
− Improve quality of life
− Promote or restore normal growth and development
− Achieve optimal response with minimal toxicity

57. ELIGIBILITY FOR ART
• All confirmed cases should be initiated on ART
but preference is given to those:
• Aged ≤ two years
• CLINICAL STAGING---stages 3 and 4
• IMMUNOLOGICAL STAGING---depending on age
and clinical staging

58. • ART should be initiated in all children with HIV,
regardless of WHO clinical stage, or at any CD4
+cell count.
• As a priority, ART should be initiated in the
following situations
– All children < 2 years of age
– All children younger than 5 years of age with WHO
clinical stage 3 or 4 disease or CD4+ cell count <750
cells/mm3 or CD4+ percentage <25%
– All children 5 years and older with WHO HIV clinical
stage 3 or 4 disease or CD4+ cell count <350
cells/mm3
– ART should be initiated in all adolescents with severe
or advanced HIV clinical disease (WHO clinical stage 3
or 4) and a CD4 + cell count of 350 cells/mm3.

59. • YET TO BE CONFIRMED, <18 MONTHS,
ANTIBODY POSITIVE, CLINICAL STAGE 3 or 4,
commence therapy while awaiting
confirmation

60. PRE ART(HAART)
• Detailed history
• Clinical examination
• CD4/CD4%
• TB SCREENING
• BASELINE TESTS

61. HAART
• NOT LESS THAN 3 DRUGS FROM AT LEAST 2
CLASSES

62. ANTI-RETROVIRAL DRUG
CLASSES
APPROVED ARV DRUGS
Nucleoside Reverse
Transcriptase Inhibitors
(NRTIs)
 Zidovudine (ZDV,
AZT)*
 Lamivudine (3TC)*
 Stavudine (d4T)*
 Abacavir (ABC)*
 Didanosine (ddI) *
 Zalcitabine (ddC)
 Emtricitabine (FTC)*
Nucleotide Reverse
Transcriptase Inhibitors
(NRTIs)
Tenofovir (Disoproxil Fumarate {TDF})
Non-Nucleoside Reverse
Transcriptase Inhibitors
(NNRTIs)
 Nevirapine (NVP)*
 Efavirenz (EFV)*
 Delavirdine (DLV)
 Etravirine (ETV) *
Fusion inhibitors  Enfuvirtide (T-20)*
Protease inhibitors (PIs)
 Lopinavir-ritonavir
(LPV/r)*
 Ritonavir (RTV) {as
pharmaco-enhancer}*
 Nelfinavir (NFV)*
 Saquinavir (SQV)
 Amprenavir (APV)*
 Indinavir (IDV)
 Atazanavir (AZV)*
 Tipranavir (TPV)
 Darunavir* (DRV)
 Fos-amprenavir* (FPV)
CCR5 inhibitor  Maraviroc
Integrase Inhibitors  Raltegravir (RAL), Dolutegravir (DTG), Elvitegravir(EVG)

63. THE WHO RECOMMENDATION
Age Group Preferred 1st line regimen Alternative 1st line
regimens
Special situations
Neonates AZT + 3TC + RAL  AZT + 3TC + NVP  AZT + 3TC + LPV/r
Children
ABC + 3TC+ DTG  ABC + 3TC
+LPV
 ABC + 3TC
+RAL
 ABC + 3TC + EFV (or
NVP)
 AZT + 3TC + EFV (or
NVP)
 AZT + 3TC + LPV/r (or
RAL)
Adolescent
 TDF + 3TC (or
FTC) + DTG
 TDF + 3TC (or
FTC) + EFV
600mg
 TDF + 3TC (or FTC) +
EFV
600mg
 TDF + 3TC (or FTC) +
EFV
400mg
 TDF + 3TC(or FTC) +
EFV
400mg
 TDF + 3TC (or FTC) +
ATV/rb
 AZT + 3TC + EFV
600mg
 TDF + 3TC (or FTC) +
PI/r
 AZT + 3TC + EFV
600mg
 TDF + 3TC (or FTC) +
RAL

64. • Effective ART results in
– recovery of the immune functions with a
progressive increase in CD4+ cell count at a rate of
50 to 100 cells/μl /year.
– Reduced occurrence of morbid conditions
– Reduced opportunistic infections
– Improved quality of life
– Promotion and restoration of normal growth and
development.
– Reduction of HIV transmission in communities

65. • NNRTIs Stop viral replication by binding to reverse
transcriptase preventing the transcription
of HIV RNA to DNA
• NRTIs Incorporate into viral DNA to stop
replication and form incomplete viral DNA
– cannot create a new virus
• NtRTIs Act at the same stage of HIV life cycle as
NRTIs, but do not require phosphorylation
for anti-HIV activity.
Classes and modes of action of ARVs

66. • Protease inhibitors (PIs) act at the last stage of HIV
cycle
– Prevent assembly and release of HIV particles from
infected CD4 cells
• Entry (fusion) inhibitors prevent HIV from infecting
CD4 T cells
• Integrase inhibitors prevent insertion of HIV DNA
template into host DNA
– Prevents viral replication
• Chemokine receptor inhibitors prevent attachment of
HIV surface antigens to CCR5 or CCX4 receptors.
Classes and modes of action of ARVs cont…

67. HIV Integrase Inhibitors
• HIV Integrase Inhibitors: Also known as
Integrase Strand Transfer Inhibitors (INSTI).
These inhibit DNA strand transfer into host-
cell genome and thus prevent viral integration.
Integrase Inhibitors do not confer resistance
to other ART classes. Examples include:
Dolutegravir (DTG), Elvitegravir(EVG),
Raltegravir (RAL).

68. HIV LIFE-CYCLE/MODE OF ACTION
OF ARVs

70. FIXED DOSE COMBINATIONS(FDC)
• AZT+3TC±NPV
• ABC+3TC
• LPV/r
• TDF/3TC/DTG
• TDF/3TC/EFV

71. AZT/3TC 60/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150 1 1
AZT/3TC/NVP 60/30/50 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150/200 1 1
ABC/AZT/3TC 60/50/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/300/150 1 1
ABC/3TC 60/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150 1 1
d4T/3TC 6/30 1 1 1.5 1.5 2 2 2.5 2.5 3 3 30/150 1 1
d4T/3TC/NVP 6/30/50 1 1 1.5 1.5 2 2 2.5 2.5 3 3 300/150/200 1 1
d4T/3TC 12/60 0.5 0.5 1 0.5 1 1 1.5 1 1.5 1.5 60/150 1 1
d4T/3TC/NVP 12/60/100 0.5 0.5 1 0.5 1 1 1.5 1 1.5 1.5 60/150/200 1 1
LPV/rb
100/25 NR NR 2 1 2 2 2 2 2 2 100/25 3 3
Drug Strength
of
Paediatric
tab (mg)
Children 6 weeks and above Strength of
Adult tab (mg)
No. of tabs
by weight
band
No. of tabs by Kg weight-band b. d.
3-5.9 6-9.9 10-13.9 14-19.9 20-24.9 25-34.5 Kg
am Pm am pm am pm Am pm am pm am pm

72. • Adverse events may vary from mild to severe or life-
threatening
• Mild toxicities
• Moderate
• Severe toxicities may require substitution with a drug
in the same class but with different toxicity profile
• Life-threatening toxicity requires discontinuation of all
ARVs and the initiation of supportive therapy.
ART toxicity profile cont…..
National Paediatric ART Training Slides Unit 6

73. ADR
• AZT anaemia PCV must not be <27%
• NPV Hypersensitivity reaction, Stevens-
Johnson syndrome
• EFV nightmares, psychosis
• ABC Severe hypersensitivity reaction.
Should carry notification card
• TDF Drug rash, potential renal toxicity, potential
decrease in bone density. Not for children
less than 8 years or with existing renal
damage.
• ABC Hypersensitivity reactions
• Read up others

74. Special considerations
• Substitution DTG for LPV/r for children with wt
of 20kg+
ABC for TDF in children younger than 8 years
• Switch to 2nd line drugs
• Salvage ---5 ARVs, 2 must be protease
inhibitors(PIs)
• Suspension
• stop

75. Routine monitoring on ART:
– Every 2 weeks for the first month after starting therapy
– Monthly for 6 months, then every 3 months thereafter.
Follow-up visit activities:
– Anthropometry (plot chart) and developmental check
– Physical exam (pallor, jaundice, mouth, skin, lymph nodes,
chest, abdomen)
– Check immunizations, assess nutrition and conduct
psychosocial assessment
– Checking for adverse ARV effects
– Review dosages for every 10% change in body weight.
Follow-up/Monitoring schedule

76. Pre-
Treatment
(Baseline)
Wk
2
Monthly x 6 Every
3 mo.
thereafter
Every
6 mo.
thereafter
1 2 3 4 5 6
Physical Exam X X X X X X X X X
Adherence
Counselling
X X X X X X X X X
Confirm HIV
status
X
HIV-1 RNA (VL) * X X X
CD4+ X X X X
FBC X X X X
E & U, Cr* X X
LFT X X** X X X
Random BS* X
Serum lipids* X
Amylase* X
Urinalysis X X X X X X X X
Chest X-ray* X
*As clinically indicated, thereafter ** To be done for children starting on NVP
Monitoring schedule for children on ARV therapy

77. PREVENTION

78. The 4-pronged approach to PMTCT
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Prevention of
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Prevention of
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Provision of Care and Suppor t for HIV
infected Children, their Mothers and Families

79. Care for the HIV exposed neonate
• Have their mouths and nostrils wiped with
gauze after delivery of the head.
• Be handled with latex gloves until maternal
blood and secretions are washed off.
• Have the cord clamped immediately after
baby is delivered and avoid milking the cord.
• Have the cord cut under cover of a lightly
wrapped gauze swab to avoid blood spurting.
• Be kept warm.

80. • Be suctioned if indicated using a
mechanical/electrical suction unit at a pressure
below 100mmhg or bulb suction. Mouth operated
suction is contraindicated.
• Be cleaned with warm chlorhexidine solution or
wiped dry with a towel or surgical cloth to remove
maternal body fluids.
• Place the baby on the mother’s chest for skin to
skin contact soon after delivery.
• In this position the baby will latch on to one of the
mother’s breast to initiate feeding unless the
mother opted for alternative feeding method.
• Have vitamin k administered, ensuring injection
safety

81. Package of services for HIV exposed children
• ARV prophylaxis
• Routine immunization and growth monitoring
and support
• Cotrimoxazole prophylaxis starting at 6 weeks
• HIV diagnostic testing using DBS for DNA PCR
at 6 to 8 weeks of age and 12 weeks after
breastfeeding has ended.
• Ongoing infant feeding counselling and
support

82. • Screening and management of tuberculosis
• Prevention and treatment of malaria
• Nutritional care and support
• Psychosocial care and support
• Antiretroviral therapy for all HIV infected
children
• Symptom management and palliative care if
needed

83. ARV Prophylaxis in neonate
• All HIV exposed infants should receive ARV prophylaxis. Infants
born to mothers with HIV who are at high risk of acquiring HIV
should receive dual prophylaxis with AZT (twice daily) and NVP
(once daily) for the first 6 weeks of life, whether they are
breastfed or formula fed.
• It is recommended that infants delivered to HIV positive
mothers who are stable on ART should receive Nevirapine
prophylaxis. Nevirapine prophylaxis is administered daily. These
infants irrespective of the type of feeding should receive daily
NVP from within 72 hours of birth to 6 weeks of age.
• If infants are receiving replacement feeding, they should be
given 4 to 6 weeks of infant prophylaxis with daily NVP (or
twice-daily AZT).

84. • For babies with weight <2,500g (0-6weeks)
– NVP 10mg or 1ml once daily
– AZT 10mg or 1ml twice daily
• For babies with weight ≥2, 500g(0-6weeks)
– NVP 15mg or 1.5ml once daily
– AZT 15mg or 1.5ml twice daily
• 6 – 12weeks
– NVP 20mg(2mls) once daily
– AZT 20mg (2mls) twice daily
• Breastfed infants who are at high risk of acquiring HIV
should continue infant prophylaxis for an additional 6
weeks (total of 12 weeks of infant prophylaxis) using
AZT (twice daily) and NVP (once daily).

85. Infant feeding in the context of HIV
• It is recommended that mothers of HIV exposed
infants breastfeed their babies exclusively for the
first six (6) months of life.
• Complementary feeds should be introduced at 6
months in addition to breast milk
• Breastfeeding complemented by household foods
should be continued till 12 months, after which
child should be weaned off breast milk.

86. Immunizations for HIV Exposed Children
• All HIV exposed children should be immunized as early
as possible to protect them against vaccine-
preventable diseases.
• Children who have, or are suspected to have HIV
infection but are not yet symptomatic should be given
all appropriate vaccines.
• Children with advanced and symptomatic HIV infection
(CD4 < 200 or < 14%, or Stage 3 or 4 disease), should
not be given live vaccines (BCG, varicella-zoster, OPV,
measles and yellow fever vaccine).
• HIV infected children should therefore be given the
inactivated polio vaccine (intramuscular).

87. • Pre exposure Prophylaxis (PrEP) is the pre-
emptive use of antiretroviral (ARV) drugs to
reduce the probability of HIV negative individuals
acquiring HIV infection especially persons who
engage in high-risk activity.
• It is recommended that PrEP should be offered
only to the category of individuals listed below
– 1. Serodiscordant couples
– 2. Commercial sex workers
– 3. Injecting drug users
– 4. Individuals who engage in anal sex on a prolonged
and regular basis

88. • Preferred daily oral dose regimen for PrEP is
the combination of TDF+ FTC (Truvada)
• The alternate regimen for PrEP is a daily dose
of TDF.
• These drugs are to be taken indefinitely until
the individual no longer qualifies as high risk

89. • Post Exposure Prophylaxis (PEP) is the short-
term use of ARV drugs to prevent HIV
infection in persons accidentally exposed to a
potential risk of acquiring HIV infection.
• This applies usually to accidental exposure as
seen in health workers or sexual assault
victims especially in cases where the HIV
status of the perpetrator cannot be readily
determined.

90. In case of a needle stick injury
• Do not squeeze or rub the injury site
• Allow blood or secretion to flow freely
• Wash exposed area immediately with soap and running
water or antiseptic solutions
• After a splash to the eye or any other mucous surface,
irrigate/rinse the exposed area immediately with water
(preferably running water) or normal saline
• Report the exposure to a senior member of staff, supervisor
or the PEP officer
• If eligible, give antiretroviral drugs recommended for post
exposure prophylaxis immediately possibly within 1 hour
and at the latest within 72 hours of the exposure (persons
presenting after 72 hours of the exposure should also be
considered for PEP).

91. • PEP is continued for 28days or the source patient
is known to be negative.
• TDF + 3TC (or FTC) is recommended as the
preferred backbone regimen for HIV post-
exposure prophylaxis for adults and adolescents.
• EFV is recommended as the preferred third drug
for HIV post-exposure prophylaxis for adults and
adolescents. However, where available, LPV/r,
RAL, or DRV/r, can be considered as alternative
options.

92. • In children <10 years AZT + 3TC is recommended
as the preferred backbone regimen for HIV post
exposure prophylaxis.
• Alternative backbone regimen for this age
category will include ABC + 3TC or TDF + 3TC (or
FTC). EFV is recommended as the preferred third
drug for HIV post-exposure prophylaxis for
children younger than 10.
• An age-appropriate alternative regimen can be
identified among LPV/r ATV/r, RAL, DRV,.

93. Recommended Schedules of
Investigations following HIV Exposure
Period Recommended Investigations
Baseline HIV, HBV, HCV screening, FBC , LFT, Renal
function test
2 weeks Full blood count, Liver function test, Renal
function test
6 weeks HIV screening
3 months HIV screening
6 months HIV screening

94. • As with all cases of sexual assault, it is
important to arrange for continuous
counselling and support for the victim.
• Emergency contraception should also be
considered.

95. Cotrimoxazole preventive therapy
(CPT)
• Cotrimoxazole preventive therapy (CPT) is a
fixed-dose combination of two antimicrobial
agents (sulfamethoxazole and trimethoprim)
used for the prevention of some AIDS-
associated opportunistic diseases
(Pneumocystis jirovecii pneumonia [PCP] and
toxoplasmosis) and the reduction of HIV-
associated mortality in people with low CD4+
cell counts.

96. • Cotrimoxazole prophylaxis is recommended
for infants, children and adolescents with HIV,
irrespective of clinical and immune conditions.
• Due to high prevalence of malaria and severe
bacterial infections in Nigeria, cotrimoxazole
prophylaxis should be continued until
adulthood, irrespective of whether ART is
provided.
• Cotrimoxazole prophylaxis is recommended
for HIV-exposed infants 6 weeks of age and
should be continued until HIV infection has
been excluded by an age-appropriate HIV test
to establish final diagnosis after complete
cessation of breastfeeding.

97. • In HIV positive individuals who have adverse
drug reactions to cotrimoxazole, options for
prophylaxis of PCP include dapsone, dapsone
plus pyrimethamine plus leucovorin and
atovaquone.
• For those who will be started on dapsone, do
a G6PD deficiency test. Dapsone should be
avoided in individuals with G6PD deficiency.

98. DOSING OF CPT
• For infants below 6 months or < 5 kg
(Cotrimoxazole 120mg daily)
• For children 6 months–5 years or 5-15 kg
(Cotrimoxazole 240 mg daily)
• For children 6–14 years old or 15–30 kg
(Cotrimoxazole 480 mg daily)
• For anyone over 14 years or >30 kgs
(Cotrimoxazole 960 mg)

99. ISONIAZID PREVENTIVE TREATMENT
OF TB
Isoniazid Preventive Therapy (IPT) is the use of
isoniazid to prevent the development of active
TB disease in HIV positive individuals.
• Paediatric recommendations:
– Children living with HIV who have poor weight
gain, fever or current cough contact history with a
TB case may have TB and should be evaluated for
TB and other conditions. If the evaluation shows
no TB, they should be offered IPT regardless of
their age .

100. • As part of a comprehensive package of HIV
prevention and care Children living with HIV who
are ≥ 12 months of age and who are unlikely to
have active TB on symptom-based screening and
have no contact with a TB case should receive six
months of IPT (10 mg/kg/day) but not more than
300mg/day.
• In children living with HIV who are < 12 months
of age, only those who have contact with a TB
case and who are evaluated for TB (using
standard lab investigations) should receive six (6)
months of IPT if the evaluation shows no TB
disease.
• All children living with HIV, after successful
completion of treatment for TB, should receive
IPT for an additional six months.