In Pakistan in 2018, 160,000 people were living with HIV. The HIV incidence rate was 0.11 per 1,000 uninfected people and HIV prevalence among adults aged 15-49 was 0.1%. Early infant diagnosis of HIV was only 2%. Diagnosis and management of pediatric HIV involves diagnostic testing, WHO clinical staging, CD4 staging, and use of antiretroviral therapy. Optimal time for starting ART is in all patients regardless of CD4 count or clinical stage. Common opportunistic infections in pediatric HIV include oral candidiasis, Pneumocystis pneumonia, and Mycobacterium avium complex.

1. Pediatric HIV managment
Dr Nehal Shah
Resident Peads ii
Services hospital lahore

2. objectives
• Understand the basics of HIV infection
• Diagnostic approach in suspected HIV patients
• Approach for use of ARVs In children
• Optimal time for initiation of ARVS
• Infant prophylaxis

4. In Pakistan in 2018:
• 160 000 people were living with HIV.
• HIV incidence per 1000 uninfected—among all people of all ages was
0.11.
• HIV prevalence—the percentage of people living with HIV—among
adults (15–49 years) was 0.1%.
• 22 000 people were newly infected with HIV.
• 6400 people died from an AIDS-related illness.
• Early infant diagnosis―tested for HIV before eight weeks of age 2% in
2018.

5. HIV Human Immunodeficiency Virus
H Infect Human beings
I Weakens Immune system and increases the risk of
infections
V Virus that attacks body
The human immunodeficiency viruses (HIV) are two species of Lentivirus
(a subgroup of retrovirus) that causes HIV infection and over time
acquired immunodeficiency syndrome (AIDS).

6. Acquired To come into possession of something new
Immune
Deficiency
Decrease or weakness in the body’s ability to fight off
infections and illnesses
Syndrome A group of signs and symptoms that occur together and
characterize a particular abnormality
AIDS is the final stage of the disease (CD4 < 200 or opportunistic infection)
AIDS Acquired Immune Deficiency Syndrome

7. HIV Structure Glycosylation
gp120
gp41
Lipid Membrane
Matrix Protein
Protease
Capsid
Viral RNA Genome
Instigrase
Reverse Transcriptase

8. HIV Entry & Replication

9. Route of transmission
• Sexual contact
• Parentral exposure to blood
• Vertical transmission from mother to child
1. intrauterine (20-30%)
2. intrapartum (70-80%)
3. postpartum (Breastfeeding ( 9-16%)

10. Infectious for HIV
blood, tissue, and specific body fluids( semen,vaginal secretions)
contaminated medical equipment, and contaminated environmental
surfaces.
NON infectious FOR HIV
Faeces, nasal secretions, saliva, sputum, sweat, tears, urine, and
vomitus are not considered infectious unless they are visibly bloody

11. Not transmitted
• Handshake
• Cough
• Sneezing
• Spitting

12. Incubation period
Period of primary infection to initial viremia (3-6weeks)
It take 2-3 months for positive serology test
Initial infection to AIDS (9m – 20yrs)
It take 10-12 years in adult to become clinicaly evident(AIDS)

13. Screen for HIV if
• Recurrent chest infections
• Non healing wounds
• Fever for more than 1 month
• Weightloss
• Diarrhea for more than 1 month
• Persistent oral thrush
• Fatigue

14. WHO Clinical Staging System
( clinical presentation)

15. Clinical Stage 1
• Asymptomatic
• Persistent Generalized Lymphadenopathy
Clinical Stage 2
• Moderate unexplained weight loss (under 10% of body weight)
• Recurrent bacterial upper respiratory tract infections (current event plus one or more in last 6 months)
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulcerations (two or more episodes in last 6 months)
• Papular pruritic eruption
• Seborrhoeic dermatitis
• Fungal nail infections

16. Clinical Stage 3
• Severe unexplained weight loss (more than 10% of body weight)
• Unexplained chronic diarrhoea for longer than 1 month
• Unexplained persistent fever (intermittent or constant and lasting for longer than 1 month)
• Oral candidiasis
• Oral hairy leukoplakia
• Pulmonary TB
• Severe bacterial infection
• (e.g. pneumonia, meningitis, empyema, pyomyositis, bone or joint infection, bacteraemia)

17. Clinical Stage 4
• HIV wasting syndrome
• Pneumocystis pneumonia .
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex virus (HSV) infection (orolabial, genital or anorectal) of more than 1 month, or visceral of any
duration
• Oesophageal candidiasis
• Extra-pulmonary TB
• Kaposi sarcoma Typical appearance in skin or oropharynx of persistent, initially flat patches with a pink or blood-bruise
colour, skin lesions that usually develop into violaceous plaques or nodules
• CMV disease (other than liver, spleen or lymph node)
• CNS toxoplasmosis
• HIV encephalopathy
• Extrapulmonary cryptococcosis (including meningitis)
• Disseminated non-tuberculous mycobacteria infection
• Progressive multifocal leukoencephalopathy (PML)
• Cryptosporidiosis (with diarrhoea lasting more than 1 month)

18. Clinical Stage 4
• Cryptosporidiosis (with diarrhoea lasting more than 1 month)
• Disseminated mycosis (coccidiomycosis, histoplasmosis)
• Recurrent non-typhoid salmonella bacteraemia
• Lymphoma (cerebral or B cell non-Hodgkin) or other solid HIV- associated tumours
• Invasive cervical carcinoma
• Visceral leishmaniasis
• HIV-associated nephropathy
• HIV-associated cardiomyopathy

19. staging based on CD4+ T Lymphocyte test
Less than 1 year 1-5 yrs More than 6 yrs
Stage Cells/ul % Cells/ul % Cells/ul %
1 >1500 >34 >1000 >30 >500 >26
2 750-1500 26-34 500-999 22-29 200-499 14-25
3 <750 <26 <500 <22 <200 <14

20. HIV Testing

21. investigations
Screening by Kit method
Virological tests
HIV RNA PCR (diagnostic)
HIV DNA PCR(not available in Pakistan)
Serology
• HIV serology by Elisa ( after 24 months of age)

22. HIV Screening Algorithm

23. 3 Kit Method
Test 1
Alerene Combo
Ag/Ab
Test 2
Uni-Gold
Ab
Test 3
Bio line
Ab

24. Other investigations before starting treatment
• CBC
• LFTS
• RFTS
• XRAY chest
• HBV and HCV serology
• CD4 count

25. ARVs Anti Retroviral Therapy

26. Ziduvidine (AZT)
Didanosine (DDI)
Lamivudine (3TC)
Abacavir (ABC)
Nucleotide Reverse
Transcriptase Inihibitors (NtRTIs)
Nucleoside Reverse
Transcriptase Inhibitors (NRTIs)
Tenofovir DF (TDF)
Non-Nuscleoside Reverse
Transcriptase Inhibitors (NNRTIs)
Nevirapine (NVP)
Efavirenz (EFV)
Protease Inhibitors
(PIs)
Lopinavir/rit (LPV/r)
Integrase Inhibitors
Raltegravir (RAL)
Dolutegavir (DTG)
ARVs

27. Mode of Action
NRTIs
NtRTIs
NNRTIs
Integrase
Inhibitors
Protease
Inhibitors
(Pis)
ARVs

28. When to start ARTs
population Recommendations
Adults and
adolescents
(≥10 years and
≥35kg)
Initiate ART in all patients regardless of CD4, clinical status and co-morbidities
Priority:
WHO Clinical Stage 3-4 and/or CD4 of less than 350 cells/mm3
Children less than 10
years or weighing
<35kg
Initiate ART in all patients regardless of CD4, clinical status and co-morbidities
Priority:
Diagnosed in first year of life
- Age less than 5 years with WHO clinical Stage 3-4 and/or CD4 of ≤ 750 cells/mm3
- Age 5 to less than 10 years with WHO clinical stage 3-4 and/or CD4 of ≤350cells/mm3
Women who are
pregnant or
breastfeeding
Initiate ART in all regardless of WHO clinical stage and CD4 cell count

29. ART regimens in children
Age Preferred regimen Alternative regimen
Younger than 3 years or less than
3.5 kg
ABC+3TC+LPV/r
AZT+3TC+NVP
AZT+3TC+LPV/r
(In case of ABC hypersensitivity)
ABC+3TC+NVP
(In case LPV/r formulation not tolerated. Caution:
both ABC and NVP can cause skin rash)
AZT + 3TC+ ABC (only while on anti-tuberculosis
therapy)
Between 3 years and 10 years ABC+3TC+EFV AZT + 3TC + EFV
(In case of ABC hypersensitivity)
TDF + 3TC + EFV
(In case of AZT toxicity)
ABC+3TC+NVP
(In case adult EFV formulation is difficult to
administer mg/kg . Caution: both ABC and NVP can
cause skin rash.
ABC+3TC+LPV/r
(Can continue regimen used below age 3 years if
clinically stable on it and tolerating ART)

30. Age Preferred regiemen Alternate regimen
Older than 10 years or more than
35 kg
TDF+3TC+EFV TDF+3TC+NVP
AZT+3TC+NVP
AZT+3TC+EFV

31. Common Side effects
Tenofovir DF (TDF)
Nephrotoxicity : Proximal Tubular Cells Dysfunction
Risk Factors :
• Underlying Renal Disease
• Underweight (BMI< 18.5)
• Untreated Diabetes Mellitus or
Hypertension
• Concomitant nephrotoxic drugs or
boosted PIs
Monitoring :
• Serial creatinine
• Glucose in Urine (dipstick method)
• Regular Growth monitoring of children
ARVs

32. Zidovudine (AZT)
Hematological toxicity : Leads to macrocytic anemia
Risk Factors :
• Base line anemia
• Neutropenia
• CD4 count <200 cells/mm3
Monitoring :
• Check Hb% before starting
• Avoid if severe anemia at baseline hb
<7 g/dl)
Common Side effects
ARVs

33. Nevaripine (NVP)
Mitochondrial toxicity : Severe hepatotoxicity
Risk Factors :
• Underlying hepatic disease
• HBV and HCV co-infection
• Concomitant use of hepatotoxic drugs.
Monitoring :
• Hepatic enzymes
Common Side effects
ARVs

34. Efavirenz (EFV)
CNS effects
Risk Factors :
• Pre-existing depression or other mental
disorder.
• Vivid dreams, anxiety, depression
• Usually resolves after a few weeks
• Can be minimized by not taking the
medication after a fatty meal.
.
Common Side effects
ARVs

35. Abacavir (ABC)
Hypersensitivity : Occurs in about 5% of the patients.
Occurs in first 14-20 days rare after 6 weeks
Presentation :
• Fever
• GI symptoms
• Malaise
• Arthalgias and myalgias
• Respiratory problems
• Rash (may be mild or absent)
Acute Syndrome :
• Resolves in 1-3 days if drug stopped
• Exacerbates if drug continued
Do not re-challange if hypersensitivity syndrome may occurs. Its fatal
Common Side effects
ARVs

36. Lopinavir/r (LPV/r)
• GI side effects
• Hypertriglyceridemia
• Fat redistribution syndrome
Common Side effects
ARVs

37. At initiation

39. Response and failure to ARTS
Clinical failure:
New or recurrent clinical event indicating advanced or severe immunodeficiency
(WHO clinical stage 3 and 4 conditions with exception of TB) after 6 months of
effective treatment
Immunological failure
Adults and adolescents
CD4 count falls to the baseline (or below) OR a persistent CD4 levels below 100
cells/mm3
Children younger than 5 years
Persistent CD4 levels below 200 cells/mm3 OR CD4 <10%
Children older than 5 years
Persistent CD4 levels below 100 cells/mm3

40. Virological failure
• Plasma VL above 1000 copies/ml (based on two consecutive viral load
measurements within a 3 - month interval, with adherence support)
after at least six months of using ARV drugs.

41. • Viral load is recommended as the preferred monitoring approach to
diagnose and confirm ART failure.
• CD4 need not be repeated if >350/mm3 and Viral loads are
suppressed.
• If viral load is not routinely available CD4 count and clinical
monitoring should be used to diagnose treatment failure.
• Second-line ART for adults and children should consist of two
nucleoside reverse-transcriptase inhibitors (NRTIs) + a ritonavir-
boosted protease inhibitor (PI) or integrase inhibitor

42. Early infant diagnosis
• HIV virological testing is diagnostic
• HIV RNA assays (specificity 100% at birth, 1, 3 and 6 months of age for
results ≥5000 copies/ml)
• Testing recommendation in Pakistan : at 6 months of age
• In USA : within 24-48 hours of birth →if negative repeat at 2-3 weeks
→4-8 weeks→4-6 months

43. Low risk group in neonates
• Mother has received ART in pregnancy > 4 weeks with viral
suppression
• Mother viral load <50copies/ml near delivery

44. High risk infants
• New HIV infection in a pregnant or breastfeed women
• HIV exposure first identified during delivery or in the postpartum
period in a breastfed infant
• pregnant woman whose viral load exceeds 1,000 copies/ml within 4
weeks prior to delivery
• If viral load testing is not available, pregnant women on ART for less
than 4 weeks

45. infant prophylaxis

46. NIH USA guidelines for infant prophylaxis
• Low risk group : AZT for 4 weeks
• High risk group: 6 weeks AZT plus 3 doses of NVP
within 48 hours of birth
48 hours after 1st dose
96 hours after 3 dose

47. DOSES IN INFANT PROPHYLAXIS
drug Birth to 6 weeks Birth to 6 weeks 6 weeks to 12 weeks
2- 2.49kg > 2.5kg
Ziduvodine (AZT)
(10mg/ml)
1ml twice daily 1.5ml twice daily 6ml twice daily
Nevirapine (NVP)
10mg/ml
1ml once daily 1.5ml once daily 2ml once daily

48. Post exposure prophylaxis
Post exposure prophylaxis (PEP) should be offered to all occupational
and non-occupational exposures within 72 hours of the exposure.
PEP should be started as early as possible and ideally within 02 hours of
the exposure and a can be given up to a maximum of 72 hours
The standard regimen of TDF+3TC (or FTC) +LPV/r is recommended for
28 day
Recheck HIV serology 6 weeks after the exposure

49. Opportunistic infections

50. Oral candidiasis
• Treatment
• Nystatin suspension(2-5ml qid )
• Oral fluconazole (3-6mg/kg qd) for 7-14days

51. pneumocystis pneumonia
• Features: acute onset of fever
• Tachypnea/dyspnea
• Hypoxemia
Daignosis
X ray findings: interstitial infiltrates, nodular lesion
Sputum/bronchoalveolar lavage fluid staining
Treatment :
TMP-SMX(15-20mg of TMP) iv till improvement
Then orally for 21 days
Steroids in moderate to severe disease
Alternate options
TMP +Dapsone
Clindamycin+primaquine

52. Indications and criteria for discontinuation of
CPT(TMP-SMZ)

53. Timing of starting ART in patients with TB/HIV co-
infection

54. Mycobacterium avium complex
Features:
• Fever,malaise,weight loss,night sweats,diarrhea,abdominal pain
Diagnosis:
• Isolation of MAC from blood,bone marrow or tissue
Treatment
Clarithromycin plus ethambutol

55. MAC prophylaxis
• MAC prophylaxis is indicated in children with
• severe immune-suppression (age <1 year with CD4 <750 cells/mm3, age 1
to <2 years with CD4 <500cells/ mm3, age 2 to <6 years with CD4 <75cells/
mm3
• age ≥6years with CD4 <50cells/mm3)
• The preferred regimen is azithromycin 20mg/kg once weekly or
clarithromycin 7.5mg/kg given twice daily.
• MAC prophylaxis cannot be discontinued in children <2 years.
• It can be discontinued after ≥6 months of ART in age 2 to <6 years with CD4
>200 cells/mm3 for >3 consecutive months, and, in age ≥ 6years with CD4
>100cells/mm3 for > 3 consecutive months.

56. Isoniazid prophylaxis
• IPT can be provided regardless of the TST status.
• Children living with HIV:
• • Who do not have poor weight gain, fever, current cough, and are unlikely to have active
tuberculosis, should be offered IPT.
• • Who are over 12 months of age, and are unlikely to have active TB, should receive 6 months of
INH preventive therapy (10 mg/kg) as part of a comprehensive package of HIV.
• • Who are over 12 months of age, and have successfully completed a course of Tuberculosis
treatment should receive INH for an additional 6 months.
• • Who have a history of contact with a TB case should receive 6 months IPT.
• • Who have poor weight gain, fever and cough, may have active tuberculosis and should be
evaluated for TB and other diseases.
• IPT for 6 months should be given to patients with HIV irrespective of the degree of
immunosuppression, and also to those on ART, those who have previously been treated for TB
and pregnant women.

57. Vaccination in PLHIV

58. BCG
Not recommended until negative test result
OPV
Recommended in endemic areas
Penta : Recommended
PCV
recommended
Measles/Rota/varicella Vaccine
Not recommended if
Severely immunosuppressed (CD4 count≤200/mm3 or CD4% ≤10%).

59. • Breast feeding ?? NO OR YES
• Blood Transfusion ?? NO plz until and unless indicated

60. Take home message
HIV is a treatable disease
U=U (undetectable = untransmittable)
don’t label HIV patient in Ward
Don’t transfuse blood until indicated