presentation on hiv in pediatrics and pptct

1. HUMAN IMMUNODEFICIENCY
VIRUS(HIV)
PRESENTER-Dr. SHASIDHAR REDDY

2. INTRODUCTION
• HIV is the virus which attacks the T-cells in the immune
system
• AIDS is the syndrome which appears in advanced stages of
HIV infection
• HIV is a virus AIDS is a medical condition
• Children experience more rapid progression than adults and
half of untreated children may die within 1st 2 years of life.

3. EPIDEMIOLOGY
• HIV epidemic in india is now in its 3rd decade and it has now
evolved from a fatal condition to that of a chronic manageable
disease.
• As per UNAIDS, in 2009, india had 2.4 million people living
with HIV,with a prevalance rate of 0.3% and over 1,70,000
died due to HIV/AIDS in 2009.
• An estimated 25,000 HIV infections occur annually among
indian children
• Most of these children were infected during
pregnancy,delivery or as soon after birth through mother-to-
child transmission.

4. • Approximately 5,000 HIV infected indian children progress to
AIDS annually.
• One out of every 25 HIV infected children worldwide lives in
india.

5. Structure of HIV
• It has a diameter of 100-120
nm with a spherical
morphology
• Cone-shaped core
surrounded by lipid matrix
containing key surface
antigens and glycoproteins
• Viral core contains 2 copies
of genomic RNA, reverse
transcriptase, integrase and
protease

6. • gag gene – encodes the matrix, capsid, nucleocapsid proteins
which are the core structural proteins
• Pol gene – encodes protease, reverse transcriptase and
integrase
• env gene – encodes a key HIV surface antigen gp160 which
consists of gp120 and gp 41

7. HIV 1
• HIV-1 is more common in
india
• Easily transmitted.
• Pathogenic in nature
• Duration of infection is
quite long.
HIV 2
• HIV-2 is found in West
Africa, Mozambique, and
Angola.
• Less easily transmitted.
• Less pathogenic.
• Duration of infection is
shorter .
• Relatively rare and has not
been reported from India.

8. TRANSMISSION
 Routes of transmission:
 Sexual transmission(0.1-1%)
 Blood and blood products(>90%)
 Occupational transmission(0.5-1%)
 Mother to fetal/infant transmission(30%)- most common in
pediatric age group

10. • Rapid progression in-
 More advanced maternal disease
 In utero infected infants
 High viral inoculum
• >4 hr duration of rupture of membranes double transmission
• Birth weight< 2,500 gm rate
• Other risk factors-
Preterm delivery,low maternal CD4 count

11. PATHOGENESIS
Due to etiological factors
HIV virus binds to CD4 receptors on surface of T cells.
RNA enters the human cell
RNA transcribes DNA by enzyme Reverse Transcriptase
Integrase inserts viral DNA into Host DNA
Viral DNA is transcribed into mRNA

12. pathophysiology cont..
mRNA is translated into protein – polyprotein
Polyprotein converts into genome and becomes permanent part of cell’s
genetic structure.
Host cell is killed as viruses are released and budding process starts.
Destruction of T- helper cells and immune response declines causing S/S.

14. CLINICAL MANIFESTATIONS
• Vary widely among infants, childrens and adolescents
• In most infants, physical examination at birth is normal
• Initial signs and symptoms may be subtle and non-specific
(eg: failure to thrive, lymphadenopathy, hepatosplenomegaly,
chronic/recurrent diarrhea, interstitial pneumonia, oral
thrush)

15. • INFANTS
• HIV encephalopathy and Oppurtunistic infections are the
early manifestations.
• Lymphadenopathy, hepatosplenomegaly
• Developmental delay
• 5-15% have no clinical and immnological manifestations.

16. • CHILDREN
• Growth failure,fever,diarrhoea
• Recurrent ear infections with sinusitis, chronic parotitis,
csom,nail infections
• Lymphadenopathy with hepatosplenomegaly

17. • ADOLESCENTS
• Growth failure, delayed puberty , cognitive dysfunction
• Cardiomyopathy
• Idiopathic thrombocytopenic purpura.

18. CLINICAL PATTERNS
• Prior to availability of the HAART three clinical patterns of HIV
disease have been described in children
1. Rapid progressors or rapid disease course (15–25%):
• Onset of AIDS occurs within the first few months of life
• median survival time-6–9 months(if left untreated)
• Opportunistic infections and neurological manifestations are
common.
• In resource-poor countries, most of HIVinfected newborns will
have this rapidly progressing disease.

19. 2. Short-term progressors or slower progression(60–80%)
• Median survival time-6 years
• slower progression
• HIV related illnesses develop by 3–4 years progressing to AIDS
by 6–7 years.
• Present clinically with
 Recurrent bacterial infections
 Failure to thrive
 Lymphoid interstitial pneumonitis (LIP).

20. 3. Long-term progressors or long-term survivors(<5%):
• No clinical or immunological progression despite long
duration of infection
• Normal CD4 and very low viral loads
• Possible mechanisms for this delay in disease manifestations
include effective humoral immunity and/or cytotoxic T
lymphocytic responses, host genetic factors, and infection
with defective virus.

21. WHO CLINICAL STAGING
HIV ASSOCIATED SYMPTOMS WHO CLINICAL STAGE
ASYMPTOMATIC 1
MILD SYMPTOMS 2
ADVANCED SYMPTOMS 3
SEVERE SYMPTOMS 4

22.  CLINICAL STAGE 1
• Asymptomatic
• Persistent generalised lymphadenopathy

23.  CLINICAL STAGE 2:
• Unexplained persistent hepatosplenomegaly
• Papular pruritic eruptions
• Fungal nail infections
• Angular chelitis
• Linear gingival erythema
• Extensive molluscum contagiosum
• Recurrent oral ulcerations
• Herpes zoster
• Chronic URTI

24. CLINICAL STAGE 3:
• Unexplained moderate malnutrition not adequately
responding to standard therapy
• Unexplained persistent diarrhoea(>14 days)
• Unexplained persistent fever(>37.5C for more than 1 month)
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Lymph node TB
• Pulmonary TB
• Severe reurrent bacterial pneumonia

25.  CLINICAL STAGE 4:
• Unexplained severe malnutrition not responding to standard
therapy
• Pneumocystis pneumonia
• Recurrent severe bacterial infection(eg: empyema , bone
infections)
• Extrapulmonary TB
• Kaposi sarcoma
• CNS toxoplasmosis
• HIV encephalopathy
• CMV retinitis

26. • Progressive multifocal leukoencephalopathy
• Symptomatic HIV-associated nephropathy or HIV-associated
cardiomyopathy.

27. DIAGNOSIS
• Serological diagnosis is difficult in infants because of presence
of maternal antibodies.
• Diagnostic tests used are
1.HIV culture -Expensive, not easily
available, requires upto 4wks to do test, not recommended
2.PCR -Preferred test to diagnose HIV in
infants and children(<18yrs), highly sensitive and specific by
2wks

28. DIAGNOSIS IN <18 MONTHS
• For children < 18 months old, both breastfed and non-
breastfed, born to a HIV positive mother — the following
testing strategy applies according to the NACO programme:
• The first HIV DNA PCR shall be conducted
at 6 weeks of age.
• If the PCR test is positive, the test is to be repeated
immediately (or as early as possible) for confirmation.

29. • If the first PCR is negative in a non-breastfed
baby, confirm with a second PCR test at 6
months.
• If the child is breastfed and initial PCR test
at 6 weeks is negative, PCR testing should be
repeated at 6–8 weeks after cessation of breastfeeding to rule
out HIV infection.
• In case of mixed -feeding the same strategy to be applied as
for a breast fed baby

30. • If symptoms develop at any time, the child
should be tested appropriately (PCR or
ELISA/rapid) at that age
• A report of “HIV Positive” is given when 2 PCR
tests are positive; and a report of “HIV negative”
is given when 2 PCR tests are negative

32. DIAGNOSIS IN >18 MONTHS
• For children ≥ 18 months old, test according to adult national
testing strategies:
• If an infant is positive at 12 months, a confirmation with a
second HIV test should be done at 18 months of age to
exclude a positive test result due to passively
transferred maternal antibodies.
• Two positive HIV antibody test results (done sequentially) in a
clinically symptomatic child(suggestive of HIV infection) more
than 18 months indicate HIV infection in the child

33. • Three positive HIV antibody test results (done
sequentially) in a clinically asymptomatic child more than 18
months old indicate the child has HIV infection.
• Two positive HIV antibody test results and one
negative result (done sequentially) in an asymptomatic child
more than 18 months old is indeterminate HIV status result.
• Follow up testing should be done in such a child to resolve the
HIV status.

34. A

35. • A presumptive diagnosis of severe HIV disease should be
made if:
 The infant is confirmed HIV antibody positive; and
 Diagnosis of any AIDS-indicator condition (s) can be made;
or
The infant is symptomatic with two or more of the following:
— Oral thrush
— Severe pneumonia;
— Severe sepsis.
• Other factors that support the diagnosis of severe HIV disease
in a HIV sero-positive infant include:
Recent HIV-related maternal death; or advanced HIV disease in
the mother(CD4 < 20%)

36. MONITORING OF HIV INFECTED CHILD

37. CD 4 COUNT ESTIMATION
• It is routinely measured in children with HIV infection
• Used to evaluate the need of initiation of therapy
• To monitor clinical progression

39. MANAGEMENT

40. • Management of HIV-infected child includes:
– Prophylaxis
– Antiretroviral therapy
– Treatment of opportunistic infections
– Adequate nutrition
– Immunization

41. COTRIMOXAZOLE prophylaxis
• Recommended for:
1. All HIV-exposed infants, starting at 4-6 weeks of
age
2. HIV-exposed breastfeeding children of any age
3. All children <1yr of age documented to be living
with HIV
4. Symptomatic children >1yr of age
*all children who begin cotrimoxazole prophylaxis
should continue until age of 5 yr, when they can be
reassessed

42. ANTIRETROVIRAL THERAPY
The currently available therapy does not eradicate the virus and
cure the child;
Rather it suppresses the virus replication for extended periods
of time
GOALS :
• To sustain full HIV Viral load suppression
• To prevent oppurtunistic infections
• To prevent progression of disease
• To allow normal growth and development

43. • NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
1st class available
Inhibit reverse transcriptase
Active against HIV 1 and 2
Act by competing with normal nucleoside triphosphates
 ZIDOVUDINE (AZT/ZDV)
 LAMIVUDINE (3TC)
 STAVUDINE (d4T)
 DIDANOSINE ( ddI)
 ABACAVIR (ABC)
 ZALCITABINE (ddC)
 EMTRICITABINE( FTC)
 TENOFOVIR ( TDF)- nucleotide reverse

44. • NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
• 2nd class
• Inhibit HIV-1 RT
• Rapidly reduces viral load
 NEVIRAPINE (NVP)
 EFAVIRENZ (EFV)
 ETRAVIRINE- second generation NNRTI
-active against HIV-1

45. • PROTEASE INHIBITORS
 Inhibit protease enzyme by binding to active site-
preventing cleavage of precursor polyproteins
 Highly potent
 Active against HIV 1 and 2
 High genetic barrier to resistance
 NELFINAVIR ( NFV)
 RITONAVIR ( RTV)
 LOPINAVIR/ RITONAVIR ( LPVr)
 AMPRENAVIR
 INDINAVIR ( IPV)
 SAQUINAVIR ( SQV)
 ATAZANAVIR
 DARUNAVIR
 TIPRANAVIR

46. New classes
• ENTRY INHIBITORS
• Inhibit viral binding/ fusion to host target cells
• Binds to gp41 glycoprotein- prevents fusion
• Ex: ENFUVIRTIDE

47. • INTEGRASE INHIBITORS
• Ex: Raltegravir , elvitegravir- integrase strand transfer
inhibitors( INSTIs)
• In MDR HIV 1
• NEWER DRUGS
• NNRTI – rilpivirine
• Integrase inhibitor- dolutegravir
• Pharmacokinetic enhancer- cobicistat

48. DURATION OF THERAPY
• HIV infection cannot be eradicated by ARV drugs
• Proviral DNA persists in sites like CNS and testes even on
treatment.
Viral load increases to pretreatment level within 2 weeks of
stoppage of therapy
Life long treatment is necessary

49. WHEN TO START ART??
• All children < 24 months of age with confirmed HIV
infection should be started on ART, irrespective of clinical or
immunological status.
• For children ages 24 - 59 months, initiate ART for all
children with
Clinical Stage 3 and Stage 4 disease
and/or
CD4 < 25% or CD4 count < 750/ mm3
• For children aged > 60 months, initiate ART for all children
with - Clinical Stage 3 and Stage 4 disease
and/or
CD4 count < 350/ mm3age.

50. WHAT TO START??
• Highly active antiretroviral therapy (HAART) is a combination
of 2 NRTIs with a PI/NNRTI
• The national program recommends a combination of
Zidovudine + Lamivudine + Nevirapine (1st line therapy)
• Alternative regimen:
Stavudine + Lamivudine + Nevirapine

51. • Drugs supplied are fixed dosed
combinations (FDC) available in India
• FDC Tablets supplied under the national initiative will cover >
5 kg children
• For children < 5 kg body weight, ARVs have to be in the form
of syrups or suspension

52. Recommendations by national programme

55. OPPORTUNISTIC INFECTIONS

56. Children having co-infection with TB
• Tuberculosis and HIV are the commonest coinfections
encountered in our country
• TB drugs alter the p450 inducer enzymes in the liver
which affects the therapeutic levels of several of the
commonly prescribed antiretroviral drugs.
• If TB is diagnosed, anti-TB treatment should be started first
and ART should be started 2–8 weeks after anti-TB treatment
is tolerated
• It decreases the risk of inflammatory immune reconstitution
syndrome (IRIS)

57.  For children on rifampicin-containing anti-TB treatment and
starting ART
Preferred regimen: 2 NRTI + EFV
(in children ≥ 3 years old)
Triple NRTI regimen
(in infants and children<2yrs)

58. HEPATITIS AND HIV
• These two may coexist in children who have transfusion
transmitted reaction
• ARV drugs causing hepatotoxicity must be avoided
• Preferred combination is
• Nevirapine + tenofovir + efavirenz

59. other opportunistic infections

63. Monitoring after starting ART
• Children may have rapid weight and height gain after ART in
addition to expected normal growth ,hence recalculate the
dose at every visit
• ART adherence assessment can be done by asking child and
parent/caregiver questions about missed dose and times the
child takes ARV
• Hemoglobin (Hb) and white blood cell count (WBC)
monitoring may be considered in children on AZT at 1, 2 and
3months
• Regular monitoring of liver function during the frst three
months of treatment may be considered for certain children
using NVP -based regimens
• If signs of clinical progression of disease are seen, CD4 should
be done

64. • The majority of common ARV related side effects is time
limited and resolve on continued ARVs with simple supportive
measures.
ᵒ Bone marrow suppression
ᵒ Anemia
ᵒ Neutropenia
ᵒ Hepatic toxicity
ᵒ Pancreatitis
o Lipodystrophy
ᵒ Peripheral neuropathy
ᵒ Hyperglycemia, Insulin resistance,diabetes
ᵒ osteopenia, osteoporosis,osteonecrosis
ᵒ Skin rash
ᵒ Hypersensitivity

65. SUPPORTIVE CARE
• Quality of life and survival of HIV infected children
• Multidisciplinary approach
• Nutritional status- dental evaluation and oral hygiene
• Development evaluated- physical occupational or speech
therapy

66. IMMUNIZATION
• The vaccines that are recommended in the national schecule
can be administered to HIV infected children except that
symptomatic HIV children should not be given oral polio and
BCG vaccines

67. PROGNOSIS
• Improved understanding and availability of more effective
ARV drugs improved prognosis
• Mortality in perinatally infected children declined >90%
• Mean age at death increased from 9 to >18 years
• Best prognostic indicators
- sustained suppression of plasma viral load
- restoration of normal CD4 count
• In resource limited countries- clinical staging system to predict
prognosis

68. • Opportunistic infections, encephalopathy or wasting
syndrome- worst prognosis- 75% die below 3 yrs
• Lymphadenopathy, splenomegaly, hepatomegaly and LIP-
better prognosis

69. PREVENTION OF MOTHER TO CHILD
TRANSMISSION(MTCT)

71. 1.Antiretroviral drug regimens for
pregnant women
• FOR THEIR OWN HEALTH, ART should be
administered irrespective of gestational
age and is continued throughout
pregnancy, delivery and thereafter
(recommended for all HIV-infected
pregnant women with CD4 cell count
<350cells/mm3 or WHO clinical stage 3 or
4)

72. Recommended regimen for pregnant women
with indication of ART is combination of…
EFV-based regimen should not be newlyinitiated
during the first trimester of pregnancy

73. Recommended regimen for pregnant women who are NOT
ELIGIBLE for ART , BUT FOR PREVENTING MTCT is…
To start ART as early as 14 weeks gestation OR as soon as
possible (when women present late in pregnancy, in labor or at
delivery)

74. For them 2 options are available….
• Option A
• For pregnant women
 antepartum daily AZT
 single dose NVP at onset of
labor
 AZT+3TC during labor or
delivery
 Twice daily AZT+ 3TC for 7
days in postpartum period.
• Option B
• For pregnant women
 triple ART from 14 wks of
gestation until 1week after
stopping breast
feeding(now stopped)
 recommended regimens
include
 AZT+3TC+LPV/r
 AZT+ 3TC+ ABC
 AZT+3TC+EFV
 TDF+3TC+ EFV

75. 2. Regimens for infants
• If mother only received AZT during antenatal period:
– For BF infants: daily NVP from birth until 1 week after all
exposure to breast milk has ended
– For non-BF infants: daily AZT/NVP from birth until 6 week
• If mother received triple drug ART during pregnancy and
entire breastfeeding:
– daily AZT/NVP from birth until 6 weeks irrespective of
feeding
Dosage:
NVP – 10mg/day (infants<2.5kg) or
15mg/day (infants>2.5kg) PO
AZT – 4mg/kg BD, PO

76. 3. Intrapartum interventions
• Delivery by elective cesarean section at 38 weeks before
onset of labor and rupture of membrane should be
considered
• Avoid artificial rupture of membrane (ARMs) unless medically
indicated
• Avoid procedures increasing risk of exposure of child to
maternal blood and secretions like use of scalp electrodes

77. 4. Breastfeeding
• Important modality of transmission of HIV infection.
• Risk of infection highest in the early months of Breast
feeding
• Increase Risks:
– Detectable levels of HIV in breast milk
– Presence of mastitis
– Low maternal CD4+ T cell count

78. • Exclusive replacement feeding is AFASS
— acceptable, feasible, affordable, sustainable and safe,
avoidance of all breast feeding is recommended.
• The mother who has chosen not to breast-feed must be able
to prepare feeds hygienically and should be advised to use
cup feeding and not bottle feeding .
• In case replacement feeding is not possible, exclusive breast-
feeding for the first six months of life with early cessation is
recommended
• Risk of transmission with mother on ART is 0.5%

79. COUNSELLING
• Voluntary counselling and testing(VCT)- preventing HIV
transmission from mother to child during childbirth
• Support for treatment of OIs
• Management of HIV TB coinfection
• Referrals to medical centres- for ART
• It is non-coercive,confidential and cost effective-
information,education and communication
• In 2006-07- VCT and PPTCT were merged to form ICTC(
integrated counselling and testing centres)

80. CONCLUSION
• ART now freely available for children- HIV children live longer
and into adolescence
• Thus newer issues in management of HIV arise- toxicities,
resistance issues and psychosocial aspects of adolescents
• Promising results in area of PPTCT- era of preventing disease
is not far

81. THANK YOU