general discussion on HIV and about recent advances and guidelines

1. Presentor- Dr. Anusha Kattula, DNB
pediatrics, St.Philomena’s hospital,
Bangalore
3-7-2015
HIV IN
CHILDREN
(RECENT GUIDELINES)

2. • HIV epidemic in India – 3rd decade
• Fatal condition---- chronic manageable disease
• Advances in treatment and prevention---- control and decrease in
disease

3. EPIDEMIOLOGY
• Globally- 3.3 million children with HIV with 3,30,000 new HIV
infections in 2011
• 2,30,000- AIDS deaths in 2011
• 17.3 million AIDS orphans
• INDIA
• 1.45 lakh children with HIV
• 1lakh- registered in ART centres
• 34,000 children- free ART
• Perinatal transmission- 5.74%

7. TRANSMISSION AND PATHOGENESIS
• 2 main types of HIV- type 1 and type 2
• HIV 1- M(main)
O(outlyer)
N( neither M nor O groups)
• M group- subtypes A-K
• Gay male epidemic in North America and Europe- B
• Subsaharan Africa- C,A,D,F,G
• INDIA- C
• HIV 2- more limited variation and less pathogenic( West Africa)

8. • HIV VIRION
• Lentivirus (member of retrovirus family)

10. • HIV TRANSMISSION
• Through mucosa of lower genital tract/ rectum- Adults
• Placenta/ GIT- infants
• Transfusion of infected blood and blood products- 3-6%
( nucleic acid amplification testing of minipools on antibody nonreactive
blood- reduced risk)
• Sexual contact- adolescent population
( 87% adolescent males with AIDS- heterosexual contact)
( 88% adolescent females with AIDS- heterosexual contact)

11. • 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

12. • >4 hr duration of rupture of membranes double transmission rate
• Birth weight< 2,500 gm
• Other risk factors-
Preterm delivery,low maternal CD4 count
• Elective LSCS + zidovudine therapy- reduces transmission by 87%

13. LIFE cycle
• Free and cell associated virion- enters mucosal tissue---- CD4cells
• Langerhan cells/dendritic cells- internalizes HIV to CD4
• HIV infects Thelper (CD4), macrophages, dendritic cells
• Co-receptors required- CCR5- macrophage lineage
- CXCR4- Tlymphocyte lineage

15. CLINICAL FEATURES
• Before HAART was available- 3distinct patterns of disease
• 15-25%- rapid disease course
• AIDS in first few months
• Median survival- 6-9 months
• Infected intrauterine
• HIV 1 culture/ viral load 11,000 copies/ml
( in first 48 hrs)
RAPID PROGRESSORS

16. • 60-80%- slower progression
• Median survival of 6 yrs
• Negative viral culture or PCR
( in first week)
• infected intrapartum
SLOW
PROGRESSORS

17. • <5%- no clinical or immunological progression
• Despite long duration of infection
• And absence of ART
• Normal CD4 and very low viral loads
• Effective humoral immunity/ defective gene virus
• “Elite survivors”-no detectable virus in blood
LONG TERM
SURVIVORS

18. • CHILDREN
• Growth failure, fever , diarrhea, secondary infections
• Mild symptoms for many years
• Recurrent ear infections with sinusitis,parotitis, chronic otitis media
• Lymphadenopathy persists
• OLDER CHILDREN
• Growth failure, delayed puberty, cognitive dysfunction
• Systemic manifestation- common

19. • hypergammaglobulinemia
• Polyclonal activation of B cells
• High levels of antiHIV-1 antibody
• Due to dysregulation of T-cell suppression of B cell antibody synthesis
• Flu or infectious mononucleosis like symptoms- at 3-6 weeks
• Due to high plasma viremia when HIV replication reaches a threshold

20. • IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME
• Increased inflammatory response from recovered immune system to
subclinical opportunistic infections
• In progressive disease and severe CD4 depletion
• NSAIDS OR corticosteroids
• May take weeks to months to subside

21. CLINICAL CATEGORIES
• CATEGORY N- not symptomatic
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

22. • CATEGORY B-moderately
symptomatic
other than those listed in A or C
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)

23. CATEGORY C- severely symptomatic
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

24. • INFECTIONS
• 20%- encapsulated organisms( strept. and salmonella)
• Bacteremia,sepsis and pneumonia
Opportunistic infections-
• Pneumocystis jirovecii- peak at 3-6 mo
• Fever, tachypnea, hypoxemia
• Chest xray- interstitial infiltrates/ diffuse alveolar disease
• Diagnosis- staining of BAL,rarely open lung biopsy
• Treatment-TMP-SMZ(15-20mg/kg/day), corticosteroids,pentamidine

26. • Atypical mycobacterium infection- MAC
• 10% if <100 CD4 count
• Fever , malaise, weight loss,night sweats,pain abdomen
• Diagnosis-isolation from blood, bone marrow or tissue
• Treatment- clarithromycin or azithromycin and ethambutol
• Oral candidiasis-most common fungal infection
• Oral nystatin suspension/ clotrimazole/fluconazole
• Disseminated histoplasmosis, coccidiomycosis, cryptococcosis are
rare
• Nitazoxanide therapy- cryptosporidia diarrhea

28. • Viral infections- herpes group
• HSV- recurrent gingivostomatitis
• VZV- resistant to acyclovir, requires foscarnet
• Disseminated CMV- <50 CD4 count
- ganicyclovir and foscarnet
• Respiratory vruses- RSV and adeno
• HPV virus

29. • CENTRAL NERVOUS SYSTEM
• 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)

30. • RESPIRATORY TRACT
• Recurrent URTI- otitis media and sinusitis
• LIP- 25% of HIV infected
• Nodular lymphoid hyperplasia in bronchial and bronchiolar
epithelium
• Chest Xray- diffuse reticulonodular pattern
• Tachypnea, cough and hypoxemia
• Oral corticosteroid therapy

32. • Pneumonias- S.pneumonia, P.aeruginosa
• Most common OI- Pneumocystis pneumonia
• CMV, aspergillus, histoplasma and Cryptococcus
• Pulmonary and extrapulmonary TB

33. • CVS
• Dilated cardiomyopathy and left ventricular hypertrophy
• Resting sinus tachycardia- 64%
• Marked sinus arrhythmias-17%
• Gallop rhythm,tachypnea and hepatospleenomegaly- best indicators
of congestive heart failure

34. • GASTROINTESTINAL AND HEPATOBILIARY TRACT
• Erythematous or pseudomembranous candidiasis, periodontal disease,
salivary gland disease, oral hairy leukoplakia
• MAC and protozoal infection
• AIDS enteropathy- malabsorption with partial villous atrophy
• Disaccharide intolerance
• Chronic/recurrent diarrhea,malabsorption, abdominal pain, dysphagia,FTT
• Supplemental enteral feeds
• pancreatitis

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

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

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

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

40. • 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

41. • HIV Culture- done from peripheral blood mononuclear cells
-equally sensitive as DNA PCR- complex and expensive
-+veresults- in 1-2 weeks
negative results- no growth for 30 days
• Sensitivity 50% at birth
90% at 3 months
• p24 antigen test- reduces detection period to 2 weeks
-cheaper highly specific, easy to perform
- less sensitive
-false negativity is high in younger children

42. TEST COMMENT
HIV DNA PCR
Preferred test to diagnose HIV-1 subtype B infection in
infants and children(<18yrs), highly sensitive and
specific by 2wks, on blood mononuclear cells
FALSE NEGATIVE-non B subtype HIV-1
HIV CULTURE
Expensive, not easily available, requires upto 4wks to
do test, not recommended
HIV RNA PCR
Less sensitive than DNA PCR- negative result cannot
exvlude HIV
Preferred test for non B subtype HIV -1

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

46. Less false negative and false
positive
Positive- 2 out of 3 bands(
p24, gp41,gp 120/160)`

48. 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 >4mon
age

49. 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

50. • 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
• Reaches adult set point by 5 years of age
• Risk of death is 2.1 times more if RNA> 1lakh copies/ml

51. HIV associated
immunodeficiency < 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

52. • ANTIRETROVIRAL THERAPY
• to decrease viral burden
• Potent inhibitors of viral replication
• Total 22ARV drugs approved- 17 for pediatric treatment
- 15 pediatric formulation
• 3 major classes – NRTIs
- NNRTIs
- PIs

53. 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

54. • NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
• 2nd class
• 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

55. 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

56. • 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
• Low dose RTV- > 6 years of age

57. 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

58. • 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

59. • 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

61. 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 DOSAGES

62. 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

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

64. • DURATION
• HIV cannot be eradicated by ARV drugs
• Proviral DNA persists in sanctuary sites CNS and testis
• Continue production of drug sensitive virus in children on HAART
• VL increases to pretreatment levels within 1-2 weeks stopping
therapy- life long treatment necessary
• Error prone RT enzyme- mutations

65. TREATMENT
• Earlier safer and simpler antiretroviral therapy can push HIV epidemic
into irreversible decline
• WHEN TO START
• Initiation of ART in all children <5yrs of age
• Increased immunological criteria of CD4 counts to <500 cells/mm3
in children >5yrs

66. New 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
 infants diagnosed in the first year of life(strong recommendation, moderate
quality evidence)
 children 1-5years( conditional recommendation,very low quality evidence)
• ART should be initiated in all HIV infected children 5 years of age and
older with CD4<500 cells/mm3 regardless of clinical stage
 CD4< 350 cells/mm3(strong recommendation, moderate quality evidence)
 CD4 between 350 and 500 cells/mm3(conditional recommendation,very low
quality evidence)

67. • 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. (strong recommendation, moderate quality evidence)
• ART should be initiated in any child younger than 18 mon of age who
has been given a presumptive clinical diagnosis of HIV infection(strong
recommendation, low quality evidence)

68. • Initiating ART at CD4>350 cells/mm3– reduces risk of progression to
AIDS, TB and increases immune recovery compared to treatment at
<350 cells

69. • 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

70. • Preferred regimens- ABC or AZT + 3TC + LPV/r
• Alternative regimen- ABC or AZT + 3TC + NVP
• Special circumstances- d4T + 3TC+ LPV/r
-d4T + 3TC + NVP

71. For 3years and older
• EFV is preferred NNRTI and NVP is alternative
• For children 3years- 10 years( adolescents<35 Kg), the NRTI should be
ABC + 3TC
AZT or TDF + 3TC
• For adolescents with HIV(10-19yrs old) and > 35 kg, the NRTI
backbone is
TDF + 3TC
AZT + 3TC
ABC + 3TC

72. Children 3y to 10 yrs and
adolescents <35 kg
Adolescents (10-19 yrs)
>35 kg
preferred ABC+ 3TC + EFV TDF + 3TC(OR FTC)+ EFV
alternatives
ABC+ 3 TC+ NVP
AZT + 3TC + EFV
AZT + 3TC + NVP
TDF + 3TC ( OR FTC) + EFV
TDF + 3TC (OR FTC) + NVP
AZT + 3TC + EFV
AZT+ 3TC+ NVP
TDF+ 3 TC(OR FTC) + NVP
SPECIAL CIRCUMSTANCES
D4t +3TC +EFV
D4t + 3TC + NVP
ABC + 3TC + EFV
ABC + 3 TC + NVP

73. • 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
• Each follow up- educate on nutrition, hygiene, adverse drug reactions

74. • 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 mon of effective treatment
• 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)

75. • 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
• 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

76. • SECOND LINE ART FOR CHILDREN( INCL. ADOLESCENTS)
• 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
• After failure of 1st line LPV/r based regimen, >3yrs children- 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

77. • 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

78. PENTA GUIDELINES 2009
(pediatric european network for treatment of AIDS)
• 0-11 months- treat all
• 12-24 months
CLINICAL- treat CDC stage B Or C
IMMUNOLOGICAL- TREAT <25% or <1000cell/micl
VIROLOGICAL- >100000copies/ml
• 24-35 months
CLINICAL- stage B orC
IMMUNOLOGICAL- -< 25% or <1000 cells/micl
VIROLOGICAL- >100000copies/ml

79. • 35-59 months
CLINICAL- Stage B or C
IMMUNOLOGICAL- Treat <20% or <500cells/micl
VIROLOGICAL- >100000copies/ml
• 5yrs+
CLINICAL- stage B or C
IMMUNOLOGICAL- <350 cells/micl
VIROLOGICAL- > 100000copies/ml

80. • PENPACT-1 TRIAL-
• To compare outcomes of ART with PI versus NNRTI containing
regimens in children
• In Europe and north/south America
• Assessed switch to second line at viral load >1000copies/ml versus
>30000copies/ml
• Concluded- both resulted in good outcomes
• Delay in switching over- more NRTI mutations

81. SIDE EFFECTS
• NRTIs
• Common- nausea, vomiting, headache, diarrhea
• Uncommon- hepatitis, fatty liver, lactic acidosis, pancreatitis,
myopathy, peripheral neuropathy,cardiomyopathy, bone marrow
suppression
• Maximum risk of panceatitis- didanosine
-peripheral neuropathy- stavudine
- lipodystrophy syndrome- stavudine
- bone marrow suppression- zidovudine

82. • NNRTIs
• Common- skin rashes, diarrhea, headache, nausea
• Uncommon- granulocytopenia, hepatotoxicity, psychosis
most neurotoxic- efavirenz
( abnormal dreams, impaired concentration, depression,
hallucination)
nevirapine can cause steven Johnson syndrome and toxic epidermal
necrolysis
NNRTIs do not cause lipodystrophy

83. • PIs
• Common- hyperglycemia, hyperlipidemia( except atazanavir),
lipodystrophy, increased transaminases, increased bleeding disorders
in hemophiliacs, osteoporosis, diabetes
Indinavir- crystalluria and kidney stones, asymptomatic hyperbilirubinemia
 azatanavir- high indirect bilirubin, prolonged PR interval
 darunavir and amprenavir- SJS
 Tesamorelin is a synthetic analogue of GH releasing factor to reduce excess
abdominal fat

84. Drugs which should not be used together
• Zidovudine + stavudine : pharmacological antagonism
• Atazanavir + indinavir : additive unconjugated hyperbilirubinemia
• Didanosine/ stavudine + zalcitabine : additive peripheral neuropathy
• Lamivudine + zalcitabine : in vitro antagonism

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

86. • IMMUNISATION
• Standard pediatric immunization
• Live oral polio vaccine – not given
• BCG should be avoided
• Varicella and MMR- can be given in not severely
immunocompromised children

88. • PROPHYLACTIC REGIMENS
• All infants between 4-6 weeks and 1yr of age proven to be HIV
infected- pneumocystis jirovecii prophylaxis(regardless of CD4)
• When child > 1year- according to CD4 count
• 150mg/m2/day of trimethoprim component of TMP/SMZ
• 1-2 daily doses, 3 days per week

89. AGE/ HIV INFECTION STATUS PCP PROPHYLAXIS CD4 MONITORING
Birth to 4-6 weeks, HIV exposed no prophylaxis none
Hiv infection reasonably
excluded
no prophylaxis none
4-6 weeks to 4 months,HIV
exposed
prophylaxis 3 mo
6 wk- 1yr, HIV infected/
indeterminate
prophylaxis 6,9 and 12 mo
1-5 yr, HIV infected prophylaxis if CD4
<500cells/micl or <15%
every 3-4 mo
>6 yr, HIV infected Prophylaxis if CD4 <200
cells/micl or <15%
every 3-4 mo

90. • Prophylaxis against MAC- azithromycin (20mg/kg) once a week PO
or clarithromycin( 7.5 mg/kg BD PO)
• Primary prophylaxis can be discontinued if immune reconstitution has
been sustained with HAART
• All HIV infected should have tuberculin skin testing for TB atleast once
per year
• IFN-gamma release assays are more specific

91. 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

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

93. PREVENTION
• Landmark pediatric clinical trails protocol- 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%
•

94. • 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
BREAST FEEDING
• WHO recommended exclusive breast feeding for atleast 6 mon
• 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

95. 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

96. • 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

97. • In sexually active adolescents- condoms to reduce STDs
• Unprotected sex, multiple partners should be avoided
• Educational efforts
• Male circumcision- 50-60% reduction in risk of HIV

98. POST EXPOSURE PROPHYLAXIS
CHILDREN >6 MONTHS
AND < 13 YEARS
>10KG
Zidovudine 9mg/kg b.d upto 300mg + lamivudine
4mg/kg b.d upto 150 mg PO + lopinavir/ ritonavir (
lopinavir 10 mg/kg/ ritonavir 2.5mg/kg upto 400/100
mg
ADOLESCENTS > 13 YRS Above regimen or
ZDV 300 mg Po b.d + 3TC 150 mg PO b.d + TDF 300mg
PO O.D
Or
ZDV 300 mg po B.D +FTC200 mg PO OD + TDF 300mg PO
OD

99. 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)

100. • 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.

102. 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

103. REFERENCES
• NELSONS TEXTBOOK
• O.P GHAI TEXTBOOK OF PEDIATRICS
• IAP TEXTBOOK OF PEDIATRIC INFECTIOUS DISEASES
• MANAGEMENT OF PEDIATRIC HIV- DR IRAH SHAH
• NACO GUDELINES 2015 FOR ARV
• INDIAN JOURNAL OF PEDIATRICS- TREATING PEDIATRIC HIV