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Pedi HIV (1).pptx
1. Pediatrics HIV
Kendalem Asmare
Leturer of Pediatrics and Child Health Nursing
At department of Pediatrics and Child Health Nursing
School of Nursing
College of Medicine and Health Sciences
University of Gondar
1
2. INTRODUCTION
• 1981: AIDS was first recognized in USA among Homosexual males
• 1983: HIV virus was isolated from a patient with lymphadenopathy
• 1984: HIV virus was clearly demonstrated to be the causative agent for
AIDS
In Ethiopia-First confirmed case-1984
• In 2003- fee based ART
• March 2005- Free ART
3. 3
Definitions
HIV
• A specific type of virus (a retrovirus) that causes AIDS
• HIV infection: w/n the virus is available/ present in ones blood. [transmit
the diseases]
• HIV disease is a chronic infectious disease caused by the Human Immune
Deficiency Virus.
• ADIS: Is a disease that limits the body’s ability to fight infection.
3
4. Epidemiology
• HIV continues to be the major global health treats claiming more
than 33 million lives so far.
• However, with increasing access to effective HIV prevention,
diagnosis, treatment and care, including for opportunistic infections,
HIV infection has become a manageable chronic health condition,
enabling people living with HIV to lead long and healthy lives.
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5. • There were 38 million people living with HIV of them 68% adult
and 53% were on ART at the end of 2019.
• Due to gaps in HIV services, 690 000 people died from HIV-
related causes in 2019 and 1.7 million people were newly
infected (FACT SHEET 2020).
6. Etiology
• HIV is caused lenti viruses, HIV-1 and HIV-2 viruses which belong to retro
virus family
• HIV 1-is responsible for most causes HIV infection
• It contains 2 copies of single stranded RNA-
• There are 2 identical region on the 2 end of the genome which contain
long terminal repeat.
• They contain regulation and expression genes.
• The remainder of the genome contain 3 sections-GAG,ENV and POL
regions
• Each of these contain many different proteins which involved in the life
cycle of the virus
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7. Transmission
• Can occurs via sexual contact, parenteral exposure to blood, or
vertical transmission from mother to child
• In pediatric vertical transmission is the commonest
• Vertical transmission of HIV can occur
intrauterine(30%-40%)
intrapartum (60-70%)
through breast-feeding (40%)
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8. Risk factors
• Maternal/ obstetric Risk factors
Low Maternal CD4 count
High viral load
Prolonged rupture of membrane(>4 hr.) and chorioaminotis
Operative vaginal delivery
Cracked nipples, breast abscess
C/S decreases the risk when viral load is>1000
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9. Neonatal risk factors
Pre term delivery <34 wks. of age
Low birth weight<2500gm
Being 1st twin in multiple px----3×
Generally with appropriate use of ART and CS and the risk of MTCT
can be reduced to less than 2%
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10. 5/10/2023 BY KENDALEM ASMARE 10
Prevention of mother to child transmission of HIV
Prong 1: Primary prevention of HIV infection
Prong 2: Prevention of unintended pregnancies among women
infected with HIV.
Prong 3: Prevention of HIV transmission from women infected
with HIV to their infants.
Prong 4: Provision of treatment, care, and support for women
infected with HIV, their infants, and their families.
11. Pathogenesis
• HIV primarily disrupt the immune system
• When the mucosa is portal of entry for HIV the first cells to be
affected are dendritic cells
• These cells process the antigen introduced and transport it to
the lymphatic tissue, but are not themselves infected
• Within the lymphoid tissue the virus selectively binds with cells
that express CD4 receptor mainly helper T cells and cells of
monocyte –macrophage lineage
• Other cells bearing CD4, such as microglia, astrocytes,
oligodendroglia are also affected
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13. conti…
- CD4+ lymphocytes migrate to the lymphatic tissue in response to viral
antigens and then become activated and proliferate, making them
highly susceptible to HIV infection.
- This antigen-driven migration and accumulation of CD4 cells within
the lymphoid tissue may contribute to the generalized
lymphadenopathy characteristic of the acute retroviral syndrome
- When HIV replication reaches a threshold (usually within 3-6 wk from
the time of infection), a burst of plasma viremia occurs.
- This intense viremia causes flu or mononucleosis-like symptoms
(fever, rash, lymphadenopathy, arthralgia) in 50-70% of infected pts.
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14. conti…
• Within 2-4 months of infections the humeral and cellular immunity
response will be established ,and there will be decrease in viral load
• And the pt will have a time of clinical latency
• Mechanisms of CD4 depletion
HIV mediated cell killing
Multineauclated giant cell(syncitia) formation b/n infected and
uninfected cells
Virus specific immune response
Super antigen mediated proliferation of T cells
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15. conti…
• Before the development of HAART 3 distinct courses were described
• Rapid progressors(15-25%)
• There is onset of AIDS and symptoms within the 1st month of life
• Median survival is 6-9 months
• Associated with intrauterine infection
• Slow progerssors(60-80%)
• Median age of survival is 6 year
• Most of them are infected intrapartum
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16. continu…
• Long term survivors(<5%)
• These have relatively normal CD4 count and low viral load for >8years
• Mechanisms-effective immunity, host genetic factor, infection with genetically
defective virus
• CD4 depletion in infant is less dramatic than adults because of relatively high
lymphocytosis- f.g CD4 count 1500 in an infant indicates immunosuppression
• Therefore CD4% has to taken for estimation of immunosuppression
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18. 18
Natural History and Clinical Manifestations of HIV
infection
1. Primary HIV Infection: Acute HIV syndrome and Sero-
conversion.
2. Asymptomatic stage – Clinical latency
3. Early Symptomatic Diseases – mild immunodeficiency
4. AIDS defining illnesses: Advanced immunodeficiency
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19. Diagnosis of HIV in infant and children
HIV test in children born to known HIV positive women
Age HIV test What a result mean Considerations
<18 months Rapid HIV anti-body test +Ve Either mother or
child’s AB
Confirm the result with
PCR
-Ve not infected if breast
feed repeat after 6 wks.
Negative may be in latter
if breast feed
HIV virologic test (DNA
PCR)
+Ve start HAART and
repeat DBS
Best to perform when the
child is 6 wks. old
-Ve never breast feed in
the last six wks. not
infected
9-12 months AB can be
used before virologic test
>18 months HIV antibody test +Ve infected
-Ve not infected
If still breast feed repeat
after 6 wks.
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20.
21. DNA PCR for Infant Diagnosis
0
10
20
30
40
50
60
70
80
90
100
sensitivity %
48 hrs 2-7 days 7-14 days 28 days
days
Dnn D, AIDS 1995, 9:F7
At 4-6 weeks of age
sensitivity of
DNA PCR is 96-98%
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22. Presumptive diagnosis
HIV antibody positive infant with
• Diagnosis of stage 4 or any AIDS defining condition OR
• Symptoms with two of the following
o Oral thrush
o Severe pneumonia
o Severe sepsis
• Supporting factors are
o Recent maternal death
o Advanced HIV disease in the mother
o Cd4 percentage of infant < 20%
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23. 23
HIV/AIDS associated illnesses /OIs
• OIs are leading causes of morbidity and mortality in HIV-infected
persons
• Most of the common OIs are preventable as well as treatable.
• Most OIs develop when the CD4 count drops below 200cells /ml
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31. ARV infant prophylaxis
For infants born to HIV infected mothers and on breastfeeding
Initiate ART for the mother.
Infants of mothers who are receiving ART and are breastfeeding
should receive 6 weeks of infant prophylaxis with daily NVP.
If the infant is considered at high risk, provide enhanced
AZT+NVP for the first 6 weeks followed by NVP alone for additional
6 weeks.
If AZT is not available, provide extended NVP alone for 12 weeks.
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32. Conti….
High-risk infants are defined as those infants:
Born to women with established HIV infection who have received less
than four weeks of ART at the time of delivery; OR
Born to women with established HIV infection with viral load >1000
copies/mL in the four weeks before delivery, if viral load measurement
available; OR
Born to women with incident HIV infection during pregnancy or
breastfeeding (incident HIV infection is new HIV diagnosis in pregnancy
or breastfeeding woman with a prior negative HIV test during pregnancy);
OR
Identified for the first time during the postpartum period with or without
HIV test prenatally .
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35. Infant feeding
If a woman has tested positive, replacement feeding is advised by
WHO if it is affordable, feasible, acceptable, sustainable and safe
(AFASS)
Otherwise, exclusive breastfeeding is recommended
In our country, excusive breastfeeding is the recommendation
Mothers should breastfeed their infants exclusively for the first 6
months of life, introducing appropriate complementary foods
thereafter, and should continue breastfeeding for the next 12 months
Mixed feeding is discouraged as its promotes transmission
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36. OI Prophylaxis
CPT(Cotrimoxazole preventive therapy)
Cotrimoxazole has activity against many pathogens (bacterial,
fungal and parasitic) that can cause disease in persons with
HIV/AIDS including:
PCP
Streptococcus pneumonia (septicemia & pneumonia)
Non typhoidal salmonella (septicemia & enteritis)
Isospora belli (enteritis)
Toxoplasma gondii (CNS infection)
Enteric gram-neg organisms (eg: E. coli, shigella species)
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37. Indications
HIV exposed infants since 4-6 week after birth
All HIV infected children <5 years regardless of CD4 value
All HIV infected children >5 yrs with:
• -Clinical stage 3 or 4 disease
• -CD4 <350
All HIV infected children with prior PCP pneumonia
Children <18 months of age with presumptive clinical diagnosis of
severe HIV disease
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38. Continu….
Discontinue also if the person has Stevens-Johnson
syndrome, severe liver disease, severe anemia, severe
pancytopenia .
Contraindications to co-trimoxazole preventive therapy:
severe allergy to sulfa drugs
severe liver disease,
severe renal disease
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39. CPT doses in infants and children
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40. IPT(isoniazid preventive therapy)
Prophylactic INH therapy should be given after ruling out active
disease to the following:
HIV infected children with positive TST>5mm
All HIV infected children who are household contacts of an active
TB case
INH should not be given to children who:
Have active or chronic hepatitis
have contraindications to INH
are suspected to have active TB
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41. Contraindications of IPT
Individuals with any one or more of the following conditions should not
receive IPT:
Symptoms compatible with tuberculosis even if the diagnosis isn’t yet
confirmed.
Active hepatitis (chronic or acute
Prior allergy or intolerance to isoniazid
Symptoms of peripheral neuropathy
NB: Past history of TB should not be contraindications for starting IPT.
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42. Antiretroviral therapy
Goals of ART:
-to restore immune function
-to maintain maximal supression of
viral replication
-to reduce HIV related mortality and
morbidity
-to improve quality of life and
prolong survival
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43. Combination therapy
ART drugs licensed as of 2010 are categorized based on their
mechanism of action
1.Reverse Transcriptase Inhibitors (RTI):
a. Nucleoside (nucleotide) RTI (NRTIs)- similar structure to
binding blocks of DNA, when incorporated into DNA, act like
chain terminators & block further incorporation of nucleosides
prevent viral DNA synthesis.
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44. b. Non-nucleoside RTI (NNRTIs)- attach to the RT & restrict its
motility, reducing activity of the enzyme.
2. Protease Inhibitors (PIs): bind to the site where the viral
peptides are cut to individual, mature, & functional core
proteins infectious virions (before leaving cells).
3. Fusion Inhibitors: the first approved being enfuvirtide, bind to
viral gp 41 & prevent fusion of the virus with the CD4+ cell &
entry to the cell.
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45. conti….
Integrase inhibitors like raltegravir block the enzyme that
catalyzes the incorporation of the viral genome into the host's
DNA.
Targeting d/t points & stages of cell activation + delivering drugs to
all tissue sites maximal viral suppression
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46. When to start ART
Start ART as early as possible to all children living with HIV
regardless of their WHO clinical stages and CD4
counts/percentage.
For HIV infected infants diagnosed with the first DNA PCR result,
initiate ART and take DBS specimen for confirmatory DNA PCR.
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47. conti…
Continue ART if the second DNA PCR confirms; whereas
if the second DNA PCR turns negative, without holding the ART, make
the 3rd DNA PCR test
For HIV infected infants and younger children, who need particular care
and support from parents and care givers, ensure the readiness and
understanding of their parents and care givers.
HIV infected infants shall be started on ART and counseling on
dosage and administration will be provided for parents.
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49. Treatment failure
3 ways of assessing treatment failure
Virologic failure-is preferred way of assessing treatment failure
-plasma viral load >1000 copies/ml in two consecutive viral load
measurements after 3 month
Clinical failure-the presence of new or recurrent stage 3 or 4
conditions(except TB) indicating severe or advanced immune
deficiency after 6 months of effective therapy and poor growth.
Immunologic failure-for children <5 year persistent CD4 count
less than 200 or 10%
For children >5 year persistent CD4 count<100
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50. Guidance for Changing ARV Regimens for treatment failure:-
• Assess adherence and address barriers
• Drug interactions
• Don’t add one drug to a failing regimen
• Consider resistance & cross resistance
• Quality of life in end stage disease
• At least 2 new drugs
• Preferably 1 new drug class
• Premature changing in ARV can limit future options
Management of ART Failure
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52. Immune reconstitution inflammatory syndrome
IRIS is a spectrum of clinical signs and symptoms thought to be
associated with immune recovery brought about by a response to
ART.
It occurs among 10–30% of the people initiating ART, usually
within the first 4–8 weeks after initiating therapy.
It may present in two different ways:
paradoxical IRIS, when an opportunistic infection or tumor
diagnosed before ART initially responds to treatment but then
deteriorates after ART starts;
or unmasking IRIS, in which initiating ART triggers disease that is
not clinically apparent before ART.
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53. management of IRIS
Patients should generally be treated for the underlying OI as soon as
possible.
Continuation of ART when IRIS occurs.
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