The document discusses management of HIV in children in India. It describes three cases: 1) a 2.5 year old girl with failure to gain weight and recurrent infections who should start ART based on her clinical staging and CD4 count, 2) a 6 year old boy with pulmonary tuberculosis who should start anti-TB treatment first before ART to reduce the risk of immune reconstitution inflammatory syndrome (IRIS), and 3) a 6 year old boy who developed anemia likely due to zidovudine toxicity and requires substitution of his antiretroviral regimen. The document provides guidelines on when to start ART in children, appropriate first-line regimens, managing drug toxicities and co-infections like tuberculosis,

1. Subhash Chettri

2. INTRODUCTION
 220,000 children infected by HIV in India
 56,700 infected HIV infants added every year
 One in every six AIDS deaths is a child
 Children represent only one in every 25 persons
getting treatment in developing countries
 Only 2,300 children are currently receiving ART in
India
NACO 2006

3. CASE 1
 2 yr and 3 m old Sarojini is HIV positive
 In the last 6m she has failed to gain wt. and ht. as
expected and suffered from 2 episodes of
pneumonia requiring hospitalisation
 She also has persistent oral thrush
 Normal developmental milestones

4.  Wt. 8 kg (3rd centile 9.6; 66% of expected)
 Ht. 75cm (3rd centile 81.9; 85% of expected)
 Cervical lymphadenopathy
 Hepatosplenomegaly
 CD4 count 500/cu. mm

5.  Should she be started on ART ?
 What are the baseline investigations needed?

6. WHO Clinical Staging
• Stage 1- Asymptomatic or Persistent generalized
lymphadenopathy

7. • Stage 2 – Mild
Unexplained persistent HSM
Unexplained parotid enlargement
Pruritic papular eruptions
Herpes zoster
Extensive warts
Extensive molluscum contagiosum
Recurrent oral ulcers
Recurrent or chronic URTI

9. WHO Clinical Staging …
• Stage 3 – Advanced
Unexplained moderate malnutrition
Unexplained persistent diarrhea
Persistent oral candidiasis
Pulmonary / LN TB
Severe recurrent bacterial pneumonia
Symptomatic LIP
Unexplained blood cytopenias
Bronchiectasis
Oral Hairy Leukoplakia

12. WHO Clinical Staging…..
• Stage 4 – Severe
Unexplained severe wasting / stunting
PCP
Extra pulmonary TB
Esophageal candidiasis
HIV encephalopathy
Unexplained severe bacterial infections
other than pneumonia
Chronic herpes simplex infection

13. Extrapulmonary cryptococcosis
Chronic cryptosporidia or isospora
CMV infection
Disseminated endemic mycosis
PMLE
Cerebral or B cell NHL
Kaposi sarcoma
HIV associated nephropathy or cardiomyopathy

16. WHO Immunological Staging

17. WHEN TO START ART?

18. Pre-ART Care

19. Anti Retroviral Therapy
 Starting ART is not an
emergency
 OIs may be an emergency
 Stabilize OIs prior to ART
 Assure responsible care giver
 It must be emphasised that
once ART is started, it must
be taken everyday lifelong
 Use pediatric formulations

20. Clinical and immunological
criteria for starting ART in
infants (< 24m)
 All infants and children <24 m with confirmed HIV
infection irrespective of clinical or immunological
stage
 Where virological testing is not available, HIV
exposed infants and children under 18m of age with
clinically diagnosed presumptive severe HIV
NACO July 2012

21.  Presumptive severe HIV
 2 or more of following
oral thrush
severe pneumonia
severe sepsis

22. Clinical and immunological
criteria for starting ART in
infants (> 24m but < 5 yr)
 All clinical stage 3 and 4
 As per CD4 counts

23. CD4 criteria of severe HIV
immunodeficiency
24-35m 36 – 59m
CD4% <20% <15%
CD4 count (cells/ cu.
mm)
<750 <350
NACO July 2012

24.  Children >5yr, adult ART guidelines is followed.
 Adult guidelines
stage 3 and 4– treat all
stage 1 and 2– treat if CD4< 350

25. Other factors influencing start of
ART
 Social environment
- care givers understand ARV therapy, possible
side effects, limitations, adherence etc.
- caregiver is ready for treatment adherence
- caregiver is actively involved in the care of the
child
- family and social support available

26.  Availability of pediatric formulations
 Consistent drug supply

27. WHAT DRUGS TO GIVE?

28. ARV DRUGS IN NATIONAL
ART PROGRAMME
NRTI NNRTI NtRTI Pis
Zidovudine
(AZT)
Nevirapine
(NVP)
Tenofovir (TFV) Atazanavir (ATV)
Stavudine (d4T) Efavirenz (EFV) Ritonavir (RTV)
Lamivudine
(3TC)
Lopinavir (LPV)
Didanosine (ddl)
Abacavir (ABC)

29. Pediatric first line ART regimens
REGIMEN DRUGS REMARKS
P I AZT + 3TC +NVP Preferred regimen for children with Hb
>9 g/dl
P I (a) d4T +3TC+NVP For children with Hb <9 g/dl
P II AZT + 3TC+EFZ For children on ATT and age >3 yrs
and wt. >10 kg
P II (a) d4T +3TC+ EFZ For children on ATT and age >3 yrs
and wt. >10 kg
And Hb < 9
NACO July 2012

30. NRTI backbone NNRTI
Zidovudine + Nevirapine
or + Lamivudine or
Stavudine + Efavirenz

31.  So Sarojini has to be started on ART based on her
clinical staging (stage 3) and immunologic staging
(severe)

32. Baseline investigations
 Hb, WBC count
 X ray chest
 BU, SE / LFT
 CD4 count – must even if the patient is
automatically eligible for ART due to clinical staging
 HBsAg / HCV
 Ophthalmologic examination

35. Case 2
 Iqbal, 6yr old HIV +ve boy presented with symptoms
of cough and low grade fever for 1m. His father was
recently detected to have PTB
 After thorough clinical examination and
investigations, Iqbal was diagnosed to be suffering
from PTB
 His CD4 count was 195/ cu.mm

36.  What is the stage of his disease?
 What should be started first ATT or ART or both
together?
 If and when ART is started, what drugs should be
used?

37. TB and HIV
 TB and HIV is the commonest coinfection
encountered in India
 Anti TB treatment should be started immediately.
ART should be started 2-8 wks later once ATT is
tolerated
 This protocol decreases risk of IRIS

38.  Both anti TB drugs and NNRTI drugs (esp NVP)
cause hepatotoxicity, therefore close monitoring is
necessary
 Rifampicin lowers NVP level by 20 to 58% and EFZ
level by 25%. It also lowers serum levels of all
protease inhibitors and should not be co
administered
 Rifampicin is the best bacteriocidal anti TB drug and
must be the part of anti TB regimen

39.  Apart from rifampicin, other anti TB drugs do not
have interaction with ART
 EFZ is the preferred drug over NVP in patients
receiving rifampicin (regimens P II and PII (a) should
be used)
 However in children < 3yrs and wt. <10 kg, EFZ is
contraindicated (3 NRTI regimen or lead in NVP with
close LFT monitoring can be used)

40.  After 2 wks of completion of ATT, EFZ should be
replaced by NVP

41. Follow up visits- clinical evaluation
 Growth monitoring – wt, ht, head circumference
 Neurodevelopment assessment
 Clinical evaluation for
detection of adverse effects
diagnosing opportunistic infections
determining efficacy of therapy
 Clinical adherence and counselling– each and every
visit

42. Monitoring and follow up of ART
NACO 2006
Day 0
/baseline
15th day 1st
month
2nd
month
6th
month
Hb Yes Yes (if on
AZT)
Yes (if
on AZT)
Yes Yes
ALT Yes Yes (if on
NVP)
Yes (if
on NVP)
Yes Yes
CD4
count
Yes Yes

43. Case 3
 6yr old, HIV +ve, boy Muthu was started on AZT+
3TC+NVP in March 2012 with baseline CD4 count
of 216/ cu.mm,
 In July 2012, he presents with history of generalised
weakness of 1m duration
 CBC: Hb 6.5 g%, WBC 4500, plt 221,000
 What is the cause of his clinical condition? What is
the management?

44. MANAGING ARV TOXICITY
 Determine the seriousness of toxicity
 Stress maintaining adherence despite toxicity
 Evaluate concurrent medications and establish
weather the toxicity is attributable to ARV or due
to some other drug taken at the same time

45.  Consider other diseases (eg. Viral hepatitis in case
of jaundice)
 If there is need to discontinue ART due to life
threatening toxicity, all ART drugs should be stopped
till patient is stabilised

46. AZT: bone marrow suppression
 Onset – few weeks to months
 Symptoms- fatigue, bacterial infections
 Risk factors
advanced HIV
high dose of AZT
preexisting anemia or neutropenia
concomitant bone marrow suppressants
(cotrimoxazole, ribavirin, ganciclovir)

47.  Treatment
substitute with d4T
identify and treat other causes of anemia
iron, erythropoietin and transfusion as indicated

48. Peripheral neuritis
 Most common drugs – d4T, ddl
 Onset- a few months after starting ART
 Numbness and paresthesia of toes and feet, may
progress to painful neuropathy of feet and calf

49. Management
 Clinical examination on every visit
 Consider discontinuation of offending drug before
pain becomes disabling– may halt progression but
symptoms may be irreversible
 Substitute ARV

50. LIPODYSTROPHY
 Umbrella term for multiple syndromes of body fat
changes
 d4T is the most common culprit
 Lipoatrophy– fat wasting in the face, upper and lower
extremities
 Lipohypertrophy– fat accumulation in the abdomen,
breast, anterior or posterior neck (buffalo hump)

52. Management
 Prevention is the best option
 Substitute d4T with AZT as soon as Hb >9 g/dl

53. Lactic acidosis
 d4T >AZT
 Severe nausea, vomiting, abdominal pain ,
breathlessness
 Elevated serum amylase, lactate and liver enzymes
with severe acidosis
 Liver biopsy shows microvesicular and
macrovesicular steatosis

54. Management
 Withdraw all ARV drugs
 Manage symptomatically – rehydration, bicarbonate
infusion
 Mechanical ventilation
 Symptoms may continue or worsen after withdrawing
drugs
 3 to 12 months may be needed for serum lactate to
return to normal
 Initiate alternate first line ART

55. IRIS (immune reconstitution
inflammatory syndrome)
 Collection of signs and symptoms associated with
immune recovery on ART
 Ability to mount immune response to antigens or
organisms
 Occurs in 10% of patients on starting ART
 25% patients with CD4 <50 cells/ cu. Mm

56.  Occurs within 2-12 weeks of initiating ART
 Clinical deterioration, unmasking of OI
 Most common IRIS events – M TB, CMV, Hepatitis
B, MAC and cryptococcal disease
 Continue ART, most resolve after a few weeks
 Short course of steroids may be needed in life
threatening reactions

57. Summary of adverse effects
Drug Most frequent significant toxicity Suggested
substitution
ABC Hypersensitivity AZT
AZT Marrrow suppression
Lactic acidosis
GI intolerance
d4t or ABC
ABC/AZT
D4t or ABC
d4T Lactic acidosis
Peripheral neuropathy
Pancreatitis
lipodystrophy
AZT or ABC
EFV Persistent and severe CNS toxicity
teratogenicity
NVP
NVP Hepatitis
Hypersensitivity
Stevens johnson syndrome
EFV
A third NRTI
PI

58. Take home message
 All children with HIV do not require ART
 Starting ART is not an emergency – stabilization of
OIs take priority
 All children < 24m or in stage 3 or 4 disease should
be started on ART
 Children >24m in stage 1 and 2, initiation of ART
should be guided by CD4 count

59.  AZT +3TC +NVP is the preferred regimen
 In children with Hb < 9 g/dl, AZT should be replaced
by d4T
 In children >3 yrs and >10 kg on ATT, NVP should be
replaced by EFZ
 Counselling should be done and adherence should
be emphasised on every visit

60. THANK YOU