HIV infection in pediatric age

group

Dr. Rugaya Elmejrab

Arab and Libyan pediatric board

Faculty of medicine Tripoli university

Pediatric infectious department Tripoli medical
center
 Etiology

HIV is a member of the genus Lentivirus

.part of the family Retroviridae

:Two types of HIV have been characterized

.HIV-1 and HIV-2

HIV-1 is more virulent, more infective, and

is the cause of the majority of HIV
.infections

The lower infectivity of HIV-2 compared

to HIV-1 is largely confined to West
.Africa
Transmission
 Mother-to-child (vertical) transmission
MTCT 90%

During Breast
Intrauterine feeding
delivery
30%_40% 30%
70%-60%

In the absence of any intervention, transmission rates

.range from 15% - 45%
:Other routes of transmission
.Parenteral exposure to blood or blood products 3-6%

.Sexual contact infrequent in pediatric

WHO recommends in developing country where other diseases
(diarrhea, pneumonia) benefit of breast feeding outweighs risk of
.HIV transmission

Risk factors that increase perinatal transmission

.Preterm<34weeks

.Low maternal antenatal CD4

.Drug abuse during pregnancy

.Prolonged rupture of membrane >4hr

.Birth weight <2.5kg

.High maternal viral load>50000 c/ml

.Mother with advanced HIV disease

.Co exciting sexually transmitted disease

Vaginal delivery, Artificial rapture of membranes, fetal scalp

monitoring, instrumental assessed delivery
Option B+: Lifelong ART for all pregnant and
breastfeeding women with HIV
 Prevention mother to child
transmission Program

HIV PREGNANT WOMAN

Already on Not Yet on Discovered just

ART ART before Delivery
Baseline VL & other
Baseline VL screenings, ART as
soon as possible Injectable ZDV
before & during
Repeat VL
Repeat VL C/S
toward3rdTM

VL undetected Increasing, consider Link to care

Decreasing,
InSTI containing
continue ART
Regimen
Delivery by
CS Injectable ZDV before
& during C/S
 HIV exposed newborn

Low risk .Replacement feeding High risk

.HBV vaccine

:Undetectable VL Do VL, and start

ZDV for 6
Repeat VL to confirm at 16 ZDV, 3TC, NVP
wk
.wk for 6 wk

Should received all postponed

VL at vaccines including live VL at
8 wk attenuated 8 wk

Undetectable, Elisa at 18
.months

:Detectable VL
Repeat to confirm but start 
.treatment immediately
Pathogenesis
HIV can infect a variety of immune cells such as CD4+ T
cells, macrophages, and microglial cells.

First cells to be infected are the dendritic cells transport HIV virus to
lymphoid tissue the viruses binds to cells expressing CD4 molecules
on their surfaces (T _ helper) monocytes macrophages microglia
.astrocytes oligodendroglia
when replication reaches threshold (usually 3_6weeks ) plasma
viremia occurs causes flulike symptoms (fever rash
lymphadenopathy arthralgia )

Early HIV replication in children has no apparent clinical

manifestation
almost all HIV infected infant have detectable HIV in peripheral
.blood by 4 months age

In adult long period of clinical latency (up to 8-12y) Which is not

indicative of viral latency as there is high virus turnover and
.CD4 lymphocytes leads to depletion of CD4
 Before HAART (highly active antiretroviral therapy)
3 distinct patterns of disease

1-Rapid disease 15-25% of infected newborn in developed

country with onset of AIDS during first few months of life if
not treated median survival time 6-9months
2-The majority of perinatally infected newborn (60-80%) present
with slower progression median survival 6y
3-Long term survivors (<5%) of perinatally infected children with
normal CD4 and low viral load
Presentation:

Should be suspected with recurrent bacterial infections

(especially invasive infections, eg, bactraemia,
meningitis, and pneumonia) and in those with unusual
infections, such as those caused by the Mycobacterium
avium-intracellulare complex (MAC).

Children with HIV infection often present with the

common bacterial infections of childhood (eg, otitis
media, sinusitis, pneumonia). but more frequent and
more severe than similar infections in immunologically
healthy children.
Growth failure, failure to thrive, or wasting
in a child may indicate HIV infection if other
common metabolic and endocrine disorders do
not appear to be the etiologies.

Failure to attain typical milestones suggests a

developmental delay.
particularly impairment in the development of
expressive language, may indicate HIV
encephalopathy.
Recurrent fungal infections,
such as candidiasis (thrush),
that do not respond to
standard antifungal agents
suggest lymphocytic
dysfunction.
Recurrent or unusually severe
viral infections, such as recurrent
or disseminated herpes simplex or
zoster infection or cytomegalovirus
(CMV) retinitis, are seen with
moderate-to-severe cellular
immune deficiency
The loss of previously attained milestones may signify
a CNS insult due to progressive HIV encephalopathy or
opportunistic infection.

In older children, behavioral abnormalities (eg, loss of

concentration and memory) may indicate HIV
encephalopathy.

Central nervous system involvement is more common

in pediatric than adult.
The developing brain in young infant is affected by
virus itself.
 CDC classification (staging) of
pediatric HIV infection
CLINICAL CLASSIFICATION

Category N: A Symptomatic or only one of the conditions

in Category A.

 
Category A: Mildly Symptomatic--two or more of the
following
*Lymphadenopathy
*Parotitis
*Hepatomegaly
*Splenomegaly
*Dermatitis
*Recurrent or persistent upper respiratory infection,
sinusitis, or otitis media
Category B: Moderately Symptomatic.

Examples of conditions in clinical Category B include but are

not limited to:

*Anemia (<8gm/DL), neutropenia (<1,000/mm3), or

thrombocytopenia (<100,000/mm3) persisting  30 days

*Bacterial meningitis, pneumonia, or sepsis (single episode

Candidiasis, oropharyngeal (thrush), persisting (> 2 months) in
children > 6 months of age

* Diarrhea, recurrent or chronic Hepatitis

*Herpes simplex virus (HSV) stomatitis, recurrent (more
than two episodes within 1 year)

*Leiomyosarcoma

*Lymphoid interstitial pneumonia or pulmonary lymphoid

hyperplasia complex.

*Nephropathy *Nocardiosis

* Persistent fever (lasting > 1 month)

* Toxoplasmosis, onset before 1 month of age

* Varicella, disseminated (complicated chickenpox)

 
Category C: Severely Symptomatic-

*Serious bacterial infections, multiple or recurrent

(i.e., any combination of at least two culture-confirmed infections within a 2-
year period) of the following types: septicemia, pneumonia, meningitis, bone
or joint infection, or abscess of an internal organ or body cavity (excluding
otitis media, superficial skin or mucosal abscesses, and indwelling catheter-
related infections

*Candidiasis, esophageal or pulmonary (bronchi, trachea, lungs)

*Coccidioi domycosis, disseminated (at site other than or in addition to lungs

or cervical or hilar lymph nodes)

*Cryptococcsis, extra-pulmonary persisting > than 1 month

*Cryptosporidiosis or isosporiasis with diarrhea

*Cytomegalovirus disease with onset of symptoms at age > 1 month (at a site
other than liver, spleen, or lymph nodes)
*Encephalopathy

(at least one of the following progressive findings present for at least
2 months in the absence of a concurrent illness other than HIV
infection that could explain the findings):

a) failure to attain or loss of develop-mental milestones or loss of

intellectual ability, verified by standard developmental scale or
neuropsychological tests;

b) impaired brain growth or acquired microcephaly demonstrated by

head circumference measurements or brain atrophy demonstrated by
CTscan or MRI (serial imagining is required for children < 2 years of
age);

c) acquired symmetric motor deficit manifested by two or more of

the following: paresis, pathologic reflexes, ataxia, or gait disturbance
* Herpes simplex virus infection causing a mucocutaneous ulcer that
persists for > 1 month; or bronchitis, pneumonitis, or esophagitis for
any duration affecting a child > 1 month of age.

*Histoplasmosis, disseminated (at a site other than or in addition to

lungs or cervical or hilar lymph nodes)

*Kaposi's sarcoma *Lymphoma, primary, in brain

*Lymphoma, small, noncleaved cell (Burkitt's), or immunoblastic

or large cell lymphoma of B-cell or unknown immunologic
phenotype
*Mycobacterium tuberculosis,
disseminated or extrapulmonary

*Mycobacterium, other species or

unidentified species,
disseminated (at a site other than or
in addition to lungs, skin, or
cervical or hilar lymphnodes
Pneumocystis carinii pneumonia*
•Toxoplasmosis of the brain with onset at > 1 month of age

*Salmonella nontyphoid) septicemia, recurrent

*Wasting syndrome in the absence of a concurrent illness

other than HIV infection that could explain the following
findings:
a) persistent weight loss > 10% of baseline OR

b) downward crossing of at least two of the following

percentile lines on the weight-for-age chart (e.g., 95th, 75th,
50th, 25th, 5th) in a child  1 year of age OR

c) < 5th percentile on weight-for-height chart on two

consecutive measurements, > 30 days apart PLUS a) chronic
diarrhea (i.e., at least two loose stools per day for  30 days
OR b) documented fever (for  30 days, intermittent or
constant)
 
 Immunological classification

Age-related CD4 values

< 12 months 1-5 years 6-12 years
Immunological category

Stage 1 1500c/mL 1000c/mL 500c/mL

No evidence of suppression 25 % 25 % 25%

Stage 2 750-1,499c/mL 500-999c/mL 200-499c/mL

Evidence of moderate % 15-24 15-24%
suppression % 15-24

Stage 3 750c/mL< 500c/mL< 200c/mL<

Severe suppression 15%< 15%< 15%<
Diagnosis

Elisa test
can be positive in uninfected newborn until
18months because Ab cross placenta

Westron blot test

HIV RNA quantitive PCR

Viral culture
Treatment

Combination of Antiretroviral drugs{ protease

inhibitor ,nucleoside reverse transcriptase, non-nucleoside
reverse transcriptase}

Does not eradicate or cure but suppress viral replication

Child <1y should start treatment what ever viral load and CD4
count

For life and good adherence

Need monitoring , resistance to treatment

Keep in mind that before initiating ART we have to treat any
opportunistic infections to prevent development of Immune
reconstitution syndrome

Prophylaxis TMP/SMZ for infected children age 6weeks to1y

regardless CD4 count or until they are proven not infected

Supportive care multidisciplinary team

Immunization

BCG and oral polio vaccines are not recommended

for HIV children. Varicella and MMR vaccines are
recommended for immune catogory1 & 2, but not for
category 3.

Influenza vaccine should be given yearly to all HIV

children older than 6 months.

Data from clinical trials are insufficient to support the

administration of rotavirus vaccine
Prognosis

The improved understanding of pathogenesis of HIV

infection in children and availability of more effective
antireroviral drugs has changed the prognosis considerably.

In general the best indicators are sustained suppression of

viral load and normal CD4 count