Hiv in pediatrics

1. HIV : AETIOLOGY AND
CLINICAL FEATURES
PRESENTOR :- Dr. Rajesh sai , 1st year Resident
MODERATOR :- Dr. Pratima , Professor
DEPARTMENT OF PEDIATRICS

2. INTRODUCTION
 There has been an estimated 70% decline in new infections in children aged
0-14 yr, largely the result of antiretroviral treatment (ART) of HIV-infected
pregnant women for the prevention of mother-to-child transmission.
 Seventy percent of adults and children with HIV infection live in sub-Saharan
Africa, where the disease continues to have a devastating impact.
 Children experience more rapid disease progression than adults, with up to
half of untreated children dying within the first 2 yr of life.
 This rapid progression is correlated with a higher viral burden and faster
depletion of infected CD4 lymphocytes in infants and children than in adults.
 Accurate diagnostic tests and the early initiation of potent drugs to inhibit
HIV replication have dramatically increased the ability to prevent and control
this disease.

3. ETIOLOGY
VIRAL CHARACTERISTICS:-
 HIV-1 and HIV-2 are members of the Retroviridae family and belong to
the Lentivirus genus
 The HIV-1 genome contains two copies of single-stranded RNA that is
9.2 kb in size
 RNA is enclosed in a capsid. Matrix is outside of the capsid
 HIV has a bilayer phospholipid membrane
with two proteins
 gp120 – involved in attachment to CD4
receptor
 gp41- involved in fusion of cellular proteins
 Each RNA copy has a reverse transcriptase enzyme

4. HIV GENOME
 At both ends of the genome there are identical regions, called LTR
(long terminal repeats), which contain the regulation and expression
genes of HIV.
 The remainder of the genome includes three major sections:
 GAG region, which encodes the viral core proteins
p24 - capsid protein: CA
p17- matrix protein: MA
p9 and p6- which are derived from the precursor p55
 POL region, which encodes the viral enzymes
reverse transcriptase [p51],
protease [p10]
integrase [p32])

5. HIV GENOME (CONTD….)
 ENV region, which encodes the viral envelope proteins
gp120 and gp41, which are derived from the precursor gp160.
 Gp120 carries highly variable V3 loop proteins an is involved in
forming neutralizing antibodies
 Antibodies against gp41 are used in diagnosis of HIV

6. Viral entry receptors
 The most important receptor is CD4
 HIV is also known as CD4 positive tropism
 CD4+ cells are found on CD4+ T cells, CD4+ macrophages and
CD4+ microglial cells
 Other receptors include
Co receptors
 CXCR4 – coreceptor in lymphocytes
 CCR5 – beta chemokine receptor involved in HIV entry in
macrophages
 Other receptors include Antibodies, Complement receptors and
direct cell to cell transmission of HIV

7. How does HIV infect the cells?
 Gp120 binds to the CD4 receptor when HIV approaches the host cell
 After viral attachment, the gp120 and CD4 molecule undergo
conformational changes
 Gp41 will then interact with the peptide receptor . It is then involved in the
initial entry of a cell(attachment of HIV is started
gp120 binds to CD4 receptor
Induces conformational changes in gp120
Also binds to coreceptors
Gp 41 interacts with peptide receptors
Initial entry of cell (Attachment)

8.  After attachment of the cell endocytosis of the cell in clathrin
coated compounds will happen
 Removal of protein envelope by use of proteases will happen
 Free viral RNA will be released
 Reverse transcriptase enzyme will then form a single stranded copy
of DNA and the ds DNA
 This ds DNA will enter the cell and get
integrated into the host cell.
 This structure is called a provirus
 This provirus become active and starts
producing viral RNA copies
 These RNA copies will be released from
the cell by budding,leading to infection,
,transmission and further spread

10. HIV 2 vs HIV 1
 HIV 2 does not have Vpu gene . Instead the Vpx gene is present.
The vpu gene in HIV 1 is involved in viral particle release and
immune regulation
 HIV 2 has a long asymptomatic period
 Lower CD4+ T cell cont
 HIV 2 is less prevalent in pediatric population
 Less mother to child transmission rates are seen in HIV 2

11. Transmission
 There are 3 modes of transmission in pediatric HIV
1. Sexual contact transmission – in adolescenece
2. Blood product related – 2 to 6 % transmission
3. Vertical transmission
 It is also called mother to child transmission (MTCT) or parent to
child transmission(PTCT)
 It is the most important mechanism of transmission
 It can happen during intrauterine life seen in about 20 – 30% of all
vertical transmission , and is most commo in late pregnancy

12.  It can happen during intrapartum period, 70% of vertical
transmission
 It can happen via postpartum transmission which can occur via
breast feeding
 This route is negligible in western countries
 In developing countries , the postpartum route accounts for about
20 – 40% of all transmissions
 The overall transmission rate via vertical transmission of HIV is
 In western countries it is 12 – 30 %
 In developing countries like asia and Africa it is upto 50%

13. RISK FACTORS FOR VERTICAL TRANSMISSION
 High maternal viral load (most important)
 In the case of preterm delivery , the risk of vertical transmission is more
 The babies of low birth weight
 Prolonged rupture of membranes lasting for >4 hours
 Low CD4+ cell count in the mother
 Elective LSCS decreases transmission by 87% if used with zidovudine
therapy in the mother and infant
 However , the additional benefit of LSCS appears negligible if the
mothers viral load is <1000 copies/ml

14. Clinical patterns of HIV
 Three clinical patterns of HIV disease have been described in children
1. Rapid progressors or rapid disease course (15–25%):
In these, the onset of AIDS occurs within the first few months of life
with a median survival time of 6–9 months (if left untreated).
 OIs and neurological manifestations are common.
 In resource-poor countries, most of HIVinfected newborns will have this
rapidly progressing disease.
2. Short-term progressors or slower progression (60–80%):
 Majority of those infected perinatally (intra partum) have a
median survival time of 6 years with slower progression
 HIV related illnesses develop by 3–4 years progressing to AIDS by 6–7 years
 They present clinically with recurrent bacterial infections, failure to thrive and
lymphoid interstitial pneumonitis (LIP)

15. 3. Long-term progressors or long-term survivors (<5%):
 Few of those perinatally infected have minimal or no progression
of disease with relatively normal CD4 counts and very low viral
loads for longer than 8 years.
 Possible mechanisms for this delay in disease manifestations
include effective humoral immunity and/or cytotoxic T lymphocytic
responses, host genetic factors, and infection with attenuated or
defective virus.

16. CLINICAL MANIFESTATIONS
 In most infants, physical examination at birth is normal.
 Initial symptoms may be subtle, such as lymphadenopathy and
hepatosplenomegaly, or nonspecific, such as failure to thrive, chronic
or recurrent diarrhea, respiratory symptoms, or oral thrush and may be
distinguishable only by their persistence.
 Whereas systemic and pulmonary findings are common in the United
States and Europe, chronic diarrhea, pneumonia, wasting, and severe
malnutrition predominate in Africa.
 Clinical manifestations found more commonly in children than adults
with HIV infection include recurrent bacterial infections, chronic
parotid swelling, lymphocytic interstitial pneumonitis (LIP), and early
onset of progressive neurologic deterioration
 Chronic parotid swelling and LIP are associated with a slower
progression of disease.

17.  The CDC Surveillance Case Definition for HIV infection is based on
the age-specific CD4+ T-lymphocyte count or the CD4+ T-
lymphocyte percentage of total lymphocytes except when a stage 3–
defining opportunistic illness supersedes the CD4 data.
 Age adjustment of the absolute CD4 count is necessary because
counts that are relatively high in normal infants decline steadily until
age 6 yr, when they reach adult norms.
 The CD4 count takes precedence over the CD4 T-lymphocyte
percentage, and the percentage is considered only if the count is
unavailable.

19. INFECTIONS
 Approximately 20% of AIDS-defining illnesses in children are recurrent bacterial
infections caused primarily by encapsulated organisms such as Streptococcus
pneumoniae and Salmonella as a result of disturbances in humoral immunity.
 Other pathogens, including Staphylococcus, Enterococcus, Pseudomonas
aeruginosa, and Haemophilus influenzae, and other Gram-positive and Gram-
negative organisms may also be seen.
 The most common serious infections in HIV-infected children are bacteremia,
sepsis, and bacterial pneumonia, accounting for more than 50% of infections in
these patients.
 Meningitis, urinary tract infections, deep-seated abscesses, and bone/joint
infections occur less frequently.
 Milder recurrent infections, such as otitis media, sinusitis, and skin and soft
tissue infections, are very common and may be chronic with atypical
presentations.

20. OPPORTUNISTIC INFECTIONS
 Opportunistic infections are generally seen in children with severe depression
of the CD4 count.
 Young children generally have primary infection and often have a more
fulminant course of disease reflecting the lack of prior immunity
 In addition, infants < 1 yr of age have a higher incidence of developing stage
3–defining opportunistic infections and mortality rates compared with older
children and adults even at higher CD4 counts, reflecting that the CD4 count
may overpredict the immune competence in young infants.
 The peak incidence of Pneumocystis pneumonia occurs at age 3-6 mo in the
setting of undiagnosed perinatally acquired disease, with the highest
mortality rate in children younger than 1 yr of age.
 Aggressive approaches to treatment have improved the outcome
substantially. Although the overall incidence of opportunistic infections has
markedly declined since the era of combination antiretroviral therapy

25. ORGAN SPECIFIC MANIFESTATIONS
RESPIRATORY TRACT
 Recurrent upper and lower respiratory tract infections (pneumonia)
are common, and complications like invasive sinusitis and mastoiditis
may also occur.
 Bronchiectasis with recurrent secondary infections may be seen
 Besides PCP, pathogens like viruses (CMV) and fungi (Aspergillus,
Histoplasma, or Cryptococcus), can be the causes
 Pulmonary and extra-pulmonary tuberculosis is an important
association.
 Lymphoid interstitial pneumonitis (LIP) can occur in up to 25% of HIV-
infected children.
 LIP is a chronic process with progressive alveolar capillary block

26.  Clinically, LIP manifests with insidious onset of cough, tachypnea,
clubbing and hypoxia with minimal rales or normal auscultatory
findings.
 Hepatosplenomegaly, lymphadenopathy and parotid enlargement
may occur.
 Chest radiograph shows chronic diffuse reticulonodular pattern
with hilar lymphadenopathy.
 Presumptive diagnosis is based on clinical and radiological
manifestations and lung biopsy is diagnostic.
 The hypoxia resolves with oral corticosteroids

27. CENTRAL NERVOUS SYSTEM
 HIV is a neurotropic virus leading to primary CNS involvement.
 Neurological manifestations can be caused by the HIV itself, OIs,
tumors or drugs.
 The manifestations vary and range from developmental delay to
progressive encephalopathy with loss or arrest of developmental
milestones, impaired brain growth (acquired microcephaly),
symmetric motor dysfunction, marked apathy, spasticity, hyper-
reflexia, abnormal plantar reflex, gait disturbance, loss of language
or motor skills, neuropsychiatric manifestations, etc.
 Older patients can have scholastic backwardness, cognitive
deterioration, behavioral problems and learning disabilities

28.  Neuroimaging reveals cerebral atrophy, increased ventricular size,
basal ganglia calcifications, leukomalacia, etc.
 HIV encephalopathy needs early initiation of treatment with highly
active anti-retroviral therapy (HAART) with drugs penetrating well in
the CNS (zidovudine, stavudine, and efavirenz).
 Focal neurologic signs and seizures are may imply a co-morbid
pathologic process (CNS tumor, OI or stroke).

29. GASTROINTESTINAL AND HEPATIC MANIFESTATIONS
 Candidiasis, periodontal disease, salivary gland disease, oral hairy
leukoplakia and oral ulcerations can occur.
 Chronic or recurrent diarrhea with malabsorption, abdominal pain,
dysphagia, and failure to thrive are common symptoms of
gastrointestinal disease.
 Gastrointestinal disease can be caused by bacteria (Salmonella,
Campylobacter, Mycobacterium Avium Intracellulare— MAC),
protozoa (Giardia, Cryptosporidium, Isospora, microsporidia), viruses
(CMV, HSV, rotavirus), or fungi (Candida).
 Infections may be localized or disseminated.
 HIV or AIDS enteropathy is the syndrome of malabsorption with
partial villous atrophy which is not associated with a specific
pathogen and has been postulated to be a result of direct HIV
infection of the gut

30.  Disaccharide intolerance is common in those with chronic diarrhea.
 Hepatomegaly is common(viral replication in reticuloendothelial
system).
 Fluctuating serum levels of transaminases with or without
cholestasis is common.
 Anti-retroviral drugs used for the treatment of OIs (like
antitubercular therapy) can also cause elevation of liver
transaminases.
 Chronic hepatitis can be caused by CMV, hepatitis B or C, or MAC
and may lead to portal hypertension or hepatic failure.
 Pancreatitis may occur due to drug therapy (pentamidine,
lamivudine) or OIs (MAC or CMV).

31. CARDIOVASCULAR SYSTEM
 Usually the cardiac involvement is clinically silent.
 Dilated cardiomyopathy, left ventricular hypertrophy, pulmonary
hypertension and congestive cardiac failure can occur.
 Resting sinus tachycardia or sinus arrhythmia, pericardial effusion,
cardiac tamponade, conduction disturbances, nonbacterial thrombotic
endocarditis, and sudden death may be seen.
 Electrocardiography and echocardiography are helpful in assessing
cardiac function.
 Supportive treatment is required (diuretics, vasodilators and
inotropes).

32. RENAL DISEASE
 Nephropathy is an unusual presenting symptom of HIV infection.
 Renal disease can occur due to HIV infection of epithelial cells,
immune-complex mediated, OIs, hyperviscosity (hyperglobulinemia) or
use of nephrotoxic drugs.
 Focal glomerulosclerosis (80%) progressing to renal failure in 6–9
months, mesangial hyperplasia (10–15%), segmental necrotizing
glomerulonephritis and minimal change disease may be seen.
 Polyuria, oliguria, hematuria and acute renal failure have also been
seen.
 Nephrotic syndrome is the most common manifestation of pediatric
renal HIV disease.
 Cases resistant to steroid therapy can be candidates for cyclosporine
therapy.

33. DERMATOLOGICAL DISORDERS
 Cutaneous manifestations seen in HIV-infected children are
inflammatory or infectious disorders which are not necessarily unique
to HIV infection.
 The disorders tend to be more disseminated and respond less
consistently to conventional therapy.
 Seborrheic dermatitis, severe eczema, recurrent or chronic episodes of
HSV, herpes zoster, molluscum contagiosum, anogenital warts,
candidial infections, tinea, onychomycosis, impetigo and scabies are
common.

34. HEMATOLOGICAL DISORDERS
 Anemia is frequent (20– 70%) and can be due to chronic infection,
inadequate nutrition (folic acid, vitamin B12 or micronutrient
deficiency), autoimmune factors, virus-associated conditions
(hemophagocytic syndrome or parvovirus B19 red cell aplasia), and
bone marrow suppression or due to adverse effect of drugs
(zidovudine).
 In those with low erythropoietin levels, subcutaneous recombinant
erythropoietin may be useful
 Leukopenia occurs in almost one-third of untreated cases (and
neutropenia often occurs).
 If anti-neutrophil antibodies are the cause, treatment with
intravenous immunoglobulin (IVIG) is useful.
 Many drugs used for treatment or OI prophylaxis or anti-retroviral
drugs (zidovudine) may also cause leucopenia or neutropenia

35.  Treatment with subcutaneous granulocyte colony-stimulating factor
can be used.
 Thrombocytopenia may occur in up to 20% of patients. It may be
immunologic (i.e. circulating immune complexes or antiplatelet
antibodies), or due to drug toxicity or idiopathic. Treatment with IVIG
or anti-D offers some improvement.
 If ineffective, a 2–3 days course of high-dose steroids is an
alternative.
 ART can also reverse the thrombocytopenia
 Patients are predisposed for thrombosis due to hyperviscosity (due
to hypergammaglobulinemia) as well as protein C and protein S
deficiency
 Clinical disease due to venous or arterial thrombosis is rare.

36. MALIGNANCIES
 As compared to adults, malignant diseases are uncommon in children.
 Non-Hodgkin lymphoma and primary CNS lymphoma are known to
occur.
 Epstein-Barr virus is associated with most lymphomas.
 Kaposi sarcoma (caused by human herpesvirus 8) is very rare in HIV-
infected children.
OTHER ORGAN INVOLVEMENT
 HIV-arthropathy, myopathy, rheumatologic, endocrine and metabolic
disorders may also be seen.

37. REFERENCES
1. NELSON TEXTBOOK OF PEDIATRICS
2. IAP TEXTBOOK OF PEDIATRICS
3. PIYUSH GUPTA PG TEXTBOOK OF PEDIATRICS

38. THANK YOU