The document provides guidelines on diagnosing and treating HIV infection in children in India. It discusses that HIV is transmitted vertically from mother to child, and outlines the various clinical categories of infection based on symptoms. It also details diagnostic approaches like PCR and viral load testing. Treatment involves lifelong antiretroviral therapy with combination drug regimens. WHO recommends initiating ART in all children under 5 regardless of symptoms or CD4 count.

1. Presented by- Surg Lt Cdr Manas R
Mishra
HIV IN CHILDREN CONSOLIDATED GUIDELINES

2.  National AIDS Control Organisation is a division of the Ministry of
Health and Family Welfare that provides leadership to HIV/AIDS
control programme in India through 35 HIV/AIDS Prevention and
Control Societies.
 In 1986, following the detection of the first AIDS case in the country,
the National AIDS Committee was constituted in the Ministry of
Health and Family Welfare.

5. TRANSMISSION AND PATHOGENESIS
 2 main types of HIV- type 1 and type 2
 HIV 1- M(main)
O(outliers)
N( neither M nor O groups)
 M group- subtypes A-K
 INDIA- C
 HIV 2- more limited variation and less pathogenic( West Africa)

6. HIV TRANSMISSION
 Through mucosa of lower genital tract/ rectum- Adults
 Vertical Transmission- infants
 Transfusion of infected blood and blood products- 3-6%
 Sexual contact- adolescent population

7. PERINATAL TRANSMISSION
 Intrauterine- placenta- 10%
 Intrapartum- vaginal fluid at time of labour- 15%
 Postpartum- breast milk- 10-15%
Rapid progression in-
 more advanced maternal disease
 In utero infected infants
 High viral innoculum

8. CLINICAL CATEGORIES
 CATEGORY N- asymptomatic
No signs / symptoms or 1 condition from category A
 CATEGORY A- mildly symptomatic
2 or more of conditions
 Lymphadenopathy
 Hepatomegaly
 Spleenomegaly
 Dermatitis
 Parotitis
 Recurrent/persistent URTI/sinusitis/otitis media

9.  Anaemia( Hb<8g/dl,
>30 neutropenia(WBC
<1000/microl) days
thrombocytopenia(1 lakh)
 Bacterial meningitis,
pneumonia/sepsis
 Candidiasis, oropharyngeal(>2mo)
 Cardiomyopathy
 CMV before 1mo of age
 Diarrhea
 Hepatitis
 HSV stomatitis(>2 episodes in 1yr)
 HSV bronchitis, pneumonitis/
esophagitis (<1 mo)
 HZ
 Leiomyosarcoma
 Lymphoid interstitial pneumonia or
primary lymphoid hyperplasia
complex
 Nephropathy
 Nocardiosis
 Persistent fever(>1 mo)
 Toxoplasmosis( before 1 mo)
 Varicella, disseminated(
complicated chickenpox)
CATEGORY B - moderately symptomatic

10.  Serious bacterial infections
 Candidiasis
(oesophageal/pulmonary)
 Coccidiomycois, disseminated
 Cryptosporidiosis or isosporiasis
with diarrhea > 1mo
 CMV after 1mo
 Encephalopathy
 HSV infection causing
mucocutaneous ulcer
 Histoplasmosis, disseminated
 Kaposi sarcoma
 Lymphoma(primary) in brain
 Lymphoma,burkitt/large cell
 Mycobacterium tuberculosis, disse
 Pneumocystis jirovecii
 Progressive multifocal
leukoencephalopathy
 Salmonella(non typhoid)
septicemia
 Toxoplasmosis after 1mo
 Wasting syndrome
CATEGORY C- severely symptomatic

11. INFECTIONS
 Bacteremia, sepsis and pneumonia
Opportunistic infections-
 Pneumocystis jirovecii- peak at 3-6 months
 Fever, tachypnea, hypoxemia
 Chest X-Ray- interstitial infiltrates/ diffuse alveolar disease
 Diagnosis- staining of BAL
 Treatment-TMP-SMZ(15-20mg/kg/day), corticosteroids, pentamidine

12. Opportunistic infections-
 Oral candidiasis-most common
fungal infection
 Oral nystatin suspension/
clotrimazole/fluconazole
 Disseminated histoplasmosis,
coccidiomycosis, cryptococcosis
are rare
 Nitazoxanide therapy-
cryptosporidia diarrhea

13.  50-90% in perinatally infected
 Subtle developmental delay to progressive encephalopathy
 Cerebral atrophy in 85% with neurological symptoms
 Focal neurological signs and seizures are unusual
 CNS lymphoma- focal neurologic signs, headache seizures
 CNS toxoplasmosis is rare
 CMV and JC virus( progressive multifocal leukoencephalopathy)
CENTRAL NERVOUS SYSTEM

14. RESPIRATORY TRACT
 Recurrent URTI- otitis media and sinusitis
 Nodular lymphoid hyperplasia in bronchial and bronchiolar
epithelium
 Chest Xray- diffuse reticulonodular pattern
 Tachypnea, cough and hypoxemia
 Oral corticosteroid therapy
 Pneumonias- S.pneumonia, P.aeruginosa
 Most common OI- Pneumocystis pneumonia
 CMV, aspergillus, histoplasma and Cryptococcus
 Pulmonary and extrapulmonary TB

15.  Focal glomerulosclerosis, mesangial hyperplasia, segmental
necrotisisng glomerulonephritis and minimal change disease
 Focal glomerulosclerosis- renal failure in 6-12mon
 Nephrotic syndrome
RENAL DISEASE

16. SKIN
 Seborrheic dermatitis or eczema
 HSV, herpes zoster,molluscum contagiosum, warts
 Allergic drug eruptions
 Epidermal hyperkeratosis

17. HEMATOLOGIC AND MALIGNANT
DISEASES
 Anaemia- 20-70%( s.c recombinant erythropoietin)
 Leukopenia-30% (GCSF)
 Thrombocytopenia-10-20% ( IVIG or anti D, steroids)
 Deficiency of clotting factors -2,7,10
Malignancies- 2%
 NHL, primary CNS lymphoma and leiomyosarcoma
 Kaposis sarcoma

18. DIAGNOSIS

19. DIAGNOSIS
 All infants of HIV infected mothers - antibody positive at birth
- upto 12-15 months
 Without any exposure- lose maternal antibody between 6 and 12 months-
Serovertors
 <18 mon- HIV DNA PCR, P24 antigen, HIV culture
 >18mon- IgG antibody to HIV- by EIA and confirmatory western blot

21. PCR
 Highly sensitive and specific
 2 types-1. qualitative
-2. quantitative
 Sensitivity is increased to 95% at 4 weeks
99% at 6 months
 Positive at birth- infected in utero
 Negative at birth and positive later- intrapartum or post partum
 Non breast fed infants- at 4-6 weeks
 Breast fed- 1-2 months after cessation of breast feeding

22.  HIV Culture- done from peripheral blood mononuclear cells
-equally sensitive as DNA PCR- complex and expensive
-+ve results- in 1-2 weeks
negative results- no growth for 30 days
 p24 antigen test- reduces detection period to 2 weeks
-cheaper highly specific, easy to perform
- less sensitive
-false negativity is high in younger children

23. DIAGNOSIS > 18 YEARS
 ELISA- reliable
- sensitivity >99.5% and specificity 99%
 Positive ELISA- confirmed by western blot

25. Viral diagnostic tests
within 1st 12-24 hrs of life
 In exposed children with negative virologic testing- additional
testing at 1-2 months and 4-6 months
 Prophylactic zidovudine- does not effect diagnostic testing
 Infection excluded if 2 negative tests with one performed at
>4months age

26. Monitoring HIV disease progression
 Immunological changes- decrease in CD4 count
- transient increase in CD8 and Total
lymphocytes
- inversion of CD4/CD8 ratio
 Plasma HIV VL, CD4 count and CD4 %- clinical course and
response to therapy

27. CD4 COUNT ESTIMATION
 To monitor clinical progression and need for initiation of therapy
 >5 years- absolute CD4 counts
 <5 years- CD4 %
HIV AND VIRAL LOAD
 Perinatally infected- progress more rapidly to disease
 No rapid fall in viremia like adults
 Risk of death is 2.1 times more if RNA> 1lakh copies/ml

28. HIV associated
immunodeficienc
y
< 11mon(
%CD4+)
12-35 mon
(%CD4+)
35- 59
mon(%CD4+)
>5 yrs( CD4+)
None/ not
significant >35 >30 >25 >500
mild 30-35 25-30 20-25 350-499
advanced 25-29 20-24 15-19 200-349
severe <25 <20 <15 <200 or <15%
WHO IMMUNOLOGICAL
CLASSIFICATION

29. Treatment

30. NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
Inhibit reverse transcriptase
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

31. NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
 Inhibit HIV-1 RT by binding to hydrophobic pocket
 Rapidly reduces viral load
 Drug resistance, cross resistance
 NEVIRAPINE (NVP)
 EFAVIRENZ (EFV)
 ETRAVIRINE- second generation NNRTI
active against HIV-1 isolates resistant to other NNRTIs

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

33. BOOSTED PI’S
 Low dose RTV- inhibitor of cyt P450 3A4 isoenzyme- inhibits
metabolism of other PI’s
 Pharmakokinetic booster
 Coformulated LPVr in children > 6 wks of age

34. New classes
ENTRY INHIBITORS ( ENFUVURTIDE)
 inhibit viral binding/ fusion to host target cells
 T20- ENFUVIRTIDE
 S.C twice daily dose-- > 6yrs
 36 a.a polypeptide binds to gp41 glycoprotein- prevents fusion
 Salvage regimen- in multi ART regimen failure

35. CCR5 CORECEPTOR ANTAGONIST ( MARAVIROC)
 Blocks CCR5 coreceptor on CD4 cell surface
 First ARV drug- does not target virus itself
 As combination in multidrug resistant HIV 1
 Should check for CCR5 tropism

36. INTEGRASE INHIBITORS
 Raltegravir and Elvitegravir- integrase strand transfer inhibitors(
INSTIs)
 In MDR HIV 1
 No pediatric formulation is commercially available
NEWER DRUGS
 NNRTI – Rilpivirine
 Integrase inhibitor- Dolutegravir
 Pharmacokinetic enhancer- Cobicistat

37. NRTI NNRTI PI
ZDV 360 mg/m2
To max 600 mg
NVP 300-400
mg/m2
Max 400 mg
NFV 110-150 mg/kg
Max 2500 mg
3TC 8 mg/kg
Max 300 mg
EFV 15 mg/kg
Max 600 mg
LPVr 460/115/m2
Max 800/200
mg
ABV 16 mg/kg
Max 600 mg
RTV 700 mg/m2
Max 1200 mg
ddI 180 mg/m2
Max 400 mg
d4T 2 mg/kg
Max 80 mg
RECOMMENDED PAEDIATRIC DOSAGES

38. FOOD INTERACTIONS
didanosine Fasting increases
absorption
Given at fasting or
2hrs after meal
saquinavir High fat meal increases
absorption
With high fat meal
Ritonavir
Atazanavir
Tipranavir
Lopinavir
darunavir
Meals increases
absorption
With meals
indinavir Fasting increases
absorption
In fasting state
etavirine Meals increase
absorption
Given after meal

39. Trends in HIV therapy
 Middle 1990s- monotherapy- immunological benefit with
treatment
 1996/97 (dual NRTIs)- combination therapy- better
immunological, clinical and viral outcomes
 Currently- HAART: highly active combination therapy- atleast 3
drugs
- enhanced survival, reduction in complications,
improved growth and quality of life

40. Recommendations ( WHO 2013)
 ART should be initiated in all children infected with HIV below 5
years of age regardless of WHO clinical stage or CD4 count
 ART should be initiated in all HIV infected children 5 years of age
and older with CD4<500 cells/mm3 regardless of clinical stage
 ART should be initiated in all children infected with HIV with severe
or advanced symptomatic disease( stage 3 or 4) regardless of age
and CD4 count.

41. WHAT TREATMENT REGIMEN TO START
WITH
 Simplified, less toxic, easy to administer “fixed drug combination”
 First line ART for children <3yrs of age
 a LPV/r based regimen should be used as first line ART for all children
infected with HIV <3yrs of age regardless of NNRTI exposure. If LPV/r is
not feasible treatment should be initiated with NVP based regimen
 Where VL monitoring is available LPV/r can be substituted with NNRTI
after virological suppression is sustained
 When children get TB while on ART with NVP or LPV/r---ABC+3TC+AZT
 For <3years the NRTI backbone should be ABC+3TC or AZT+3TC

42. First-line ART
Preferred
first-line regimens
Alternative
first-line Regimens
Adults
(including pregnant and
breastfeeding women and
adults with TB and HBV
coinfection) TDF + 3TC (or FTC) + EFV
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC (or FTC) + NVP
Adolescents
(10 to 19 years) ≥35 kg
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC (or FTC) + NVP
ABC + 3TC + EFV (or NVP)
Children 3 - 10 years and
adolescents <35 kg
ABC + 3TC + EFV
ABC + 3TC + NVP
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC (or FTC) + EFV
TDF + 3TC (or FTC) + NVP
Children <3 years
ABC or
AZT + 3TC + LPV/r
ABC + 3TC + NVP
AZT + 3TC + NVP
NEW
New guidelines promote further simplification of ART delivery by reducing the number of preferred first-line
regimens.

43. TREATMENT ASSESSMENT AND LABORATORY
MONITORING
 Before ART is initiated thorough clinical and basic lab
assessment should be undertaken
 Adherence , toxicities and treatment failures
 Childs nutritional status, growth and development, comorbidities
and immunization status
 The CD4 count has to be checked baseline and at 12 monthly
intervals before initiation of ART
 While on ART- CD4 monitored once in every 6 months
 Each follow up- educate on nutrition, hygiene, adverse drug
reactions

44. FAILURES
CLINICAL FAILURE
 Occurrence of new/ recurrent clinical event indicating advanced or
severe immunodeficiency(WHO clinical stage 3 or 4 with exception
of TB) after 6 months of effective treatment
VIROLOGICAL FAILURE
 Persistently detectable viral load exceeding >1,000 copies/ml in 2
consecutive measurements within 3 month interval after atleast 6
months of ART

45. IMMUNOLOGICAL FAILURE
 In <5yrs-Persistently low CD4 levels below 200 cells/mm3 or < 10%
 In > 5yrs, including adolescents- CD4 falling below baseline or
persistently < 100 cells/mm3( in absence of recent infection)

46.  After failure of first line NNRTI regimen, a boosted PI plus 2 NRTIs
are recommended- LPV/r is boosted PI
 After failure of first line LPV/r regimen
 Children < 3yrs - should remain on 1st regimen
 Children >3yrs - 2nd line- NNRTI + 2 NRTIs ( EFV is preferred NNRTI)
 After failure of first line regimen ABC or TDF + 3TC, preferred NRTI
backbone option is AZT + 3TC
 After failure of AZT or d4T + 3TC, preferred NRTI backbone option is
ABC or TDF + 3TC
2nd LINE ART FOR CHILDREN

47. 3rd LINE ART FOR CHILDREN
 Newer drugs such as Etravirine( ETV), DRV and Raltegravir(RAL)
 Choice of PI is DRV/r after treatment failure with LPV/r or ATV/r
 Children with failing 2nd line with no new options should continue on
tolerated regimen

48. 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

49.  Adults and adolescents living with HIV should be screened for TB
with a clinical algorithm; those who report any one of the symptoms
of current cough, fever, weight loss or night sweats may have
active TB and should be evaluated for TB and other diseases
 Children living with HIV who have any of the following symptoms of
poor weight gain, fever or current cough or contact history
with a TB case may have TB and should be evaluated for TB and
other conditions. If the evaluation shows no TB, children should be
offered ISONIAZID preventive therapy regardless of their age
Tuberculosis and HIV

50.  TB patients with known positive HIV status and TB patients living in
HIV-prevalent settings should receive at least six months of
Rifampicin treatment regimen
 Xpert MTB/RIF should be used as the initial diagnostic test in
individuals suspected of having HIV-associated TB or multidrug-
resistant TB

51.  Adults and adolescents living with HIV should be screened
with a clinical algorithm; those who do not report any one of
the symptoms of current cough, fever, weight loss or night
sweats are unlikely to have active TB and positive tuberculin
skin test should be offered IPT
 Duration 6 months
 IPT should be given to such individuals irrespective of the
degree of immunosuppression, and also to those on ART,
those who have previously been treated for TB and pregnant
women
Isoniazid preventive therapy (IPT)

52.  In children living with HIV who are less than 12 months of
age, only those who have contact with a TB case and who
are evaluated for TB (using investigations) should receive six
months of IPT if the evaluation shows no TB disease
 All children living with HIV, after successful completion of
treatment for TB disease, should receive isoniazid for an
additional six months

53.  ART should be started in all TB patients, including those with
drug-resistant TB, irrespective of the CD4 count
 Antituberculosis treatment should be initiated first,
followed by ART as soon as possible within the first 8 weeks
of treatment
 The HIV-positive TB patients with profound immuno-
suppression (such as CD4 counts less than 50 cells/mm3)
should receive ART immediately within the first two weeks of
initiating TB treatment
Timing of ART co-infected with TB

54.  Efavirenz should be used as the preferred NNRTI in patients
starting ART while on antituberculosis
 WHO recommends ART for all patients with HIV and drug-resistant
TB, requiring second-line anti-tuberculosis drugs irrespective of
CD4 cell count, as early as possible

55.  HBV
1. Start ART regardless of CD4 count
2. Use of at least two agents with activity against HBV
(TDF + 3TC or FTC)
 HCV
ART among people coinfected with HCV should follow the
same principles as in HIV monoinfection.
HIV with HBV and HCV

56. Prevention in children

57. WHO’s 4-Component Strategy for MTCT Prevention
Prevention of
HIV in women,
especially
young women
Prevention of
unintended
pregnancies in
HIV-infected
women
Prevention of
transmission
from an HIV-
infected woman
to her infant
Support for HIV-
infected women,
their infants, and
families
Component
1
Component
2
Component
3
Component
4

58. PREVENTION
 ZDV prophylaxis to pregnant women as early as 4 wks of gestation,
during labor and delivery and to newborn for 1st 6 weeks- reduced
transmission by 75%
 Maternal HAART – decreases transmission to <2%
 Elective LSCS and maternal zidovudine- reduces transmission by
87%
 Single dose NVP- once to mother in labour and to infant in 48-72
hrs- reduces by 50%
 Who do not meet indications for therapy- ZDV from 14 wks+/- SD
NVP during labor and oral ZDV+ 3TC during labor and 1 wk
postpartum infants ZDV/NVP for 6 weeks

59. BREAST FEEDING
 WHO recommended exclusive breast feeding for atleast 6 months
 Treat mothers with triple ART and infants with daily nevirapine ( upto
6wks) –reduces risk to 2%
 Others with high CD4- discontinue ART 1 wk after delivery and treat
infant with daily nevirapine

60. United Nations
SCN News
May 1991
“Use my picture
if it will help,
“I don’t want
other people to
make the same
mistake”.
Breast Feeding vs Bottle Feeding

61. Simplified Infant Prophylaxis doses
Drug Infant age Daily dosing
NVP
Birth to 6 weeks
• Birthweight 2000−2499 g
• Birthweight ≥2500 g
10 mg once daily
15 mg once daily
> 6 weeks to 6 months 20 mg once daily
> 6 months to 9 months
30 mg once daily
> 9 months until breastfeeding ends
40 mg once daily
AZT
Birth to 6 weeks
• Birthweight 2000−2499 g
• Birthweight ≥2500 g
10 mg twice daily
15 mg twice daily
If toxicity from NVP requires discontinuation or if NVP is not available, infant 3TC can be
substituted.

62. COMPONENTS OF THE CARE PACKAGE
1. Interventions for all infants and
children to aid survival
2. Survival interventions for
infants and children who are
exposed to HIV
3. Survival interventions for infants
and children who are infected
with HIV
All children
HIV exposed
children
HIV pos
children

63. Interventions for all children to aid survival
• Newborn care, including
– Skilled care at birth
– Early initiation of exclusive breastfeeding
– Early postnatal visit
• Prevention interventions, including
– Exclusive breastfeeding up to 6 months of age
– Good maternal nutrition
– Growth monitoring
– Complete, timely immunization
• Treatment interventions, including
– Oral rehydration therapy for diarrhoea
– Prompt treatment for pneumonia and malaria

64. Survival interventions for infants and children who are
exposed to HIV
 Antiretroviral prophylaxis (maternal and infant)
 Provider-initiated HIV testing,
including infant viral testing
 Early and regular clinical assessment
 Co-trimoxazole prophylaxis
 Counseling and support around
nutrition and infant feeding
 Care, treatment and support for family members

65. Survival interventions for infants and children who
have HIV
 Early antiretroviral therapy and follow-up care
 Adherence and treatment support
 Regular clinical and laboratory monitoring
 Psychosocial support
 TB screening, prevention and management

66. Survival interventions for infants and children who
have HIV (cont.)
 Nutrition, infant and young child feeding
 Macronutritional support, vitamin supplementation, regular growth
monitoring
 Management of severe malnutrition
 Prevention, active early detection and management of opportunistic
infections
 Pneumonia, diarrhoea, malaria
 Additional Immunizations

67. WHO recommendations for PPTCT
 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 & days
postpartum
 Option B
 For pregnant women
 triple ARV from 14 wks of
gestation until 1week after
stopping breast feeding
 recommended regimens include
 AZT+3TC+LPV/r
 AZT+ 3TC+ ABC
 AZT+3TC+EFV
 TDF+3TC+ EFV

68. For infants
 If breast feeding;single dose NVP at birth upto cessation of Breast
feed (1 week)
 If not breast feeding, single dose NVP at birth and upto 4-6 weeks
of age
 Daily administration of AZT or NVP from birth until 4-6 weeks of
age

69. 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

70. REFERENCES
 WHO/ UNAIDS Guidelines
 Nelsons Textbook Of Pediatrics- - 20e
 O.P Ghai Textbook Of Pediatrics- 8e
 IAP Textbook Of Pediatric Infectious Diseases
 NACO Guidelines 2015 FOR ARV
 Indian Journal Of Pediatrics- Treating Pediatric HIV