1. HIV infection in children
O.O.Bogomolets National Medical University department of pediatric infection diseases
HIV infection in children
Yevtushenko V.

2. Definitions HIV – human immunodeficiency virus.
AIDS - acquired immune deficiency syndrome.
Opportunistic infection - an infection by a microorganism that normally does not cause disease but becomes pathogenic when the body's immune system is impaired and unable to fight off infection.

3. Etiology
There are two subtypes of HIV: HIV-1 (distributed worldwide) and HIV-2 (primarily confined to West Africa).
HIV is a member of the genus Lentivirus, part of the family of Retroviridae

4. International Statistic
Approximately 34 million people living with HIV in 2011 (WHO).
2.5 million people became newly infected in 2011.
1.7 million died of AIDS-related causes, including children.

5. Adults and children estimated to be living with HIV, 2007

6. Routes of transmission
Sexual contact (most frequent in adults).
Via blood and blood products.
Mother-to-child (about 90% of cases of HIV in children) - during pregnancy, during delivery, or through breast milk.

7. Mother-to-child transmission
Commonest route of HIV spreading in children.
The risk of transmission before or during birth is around 20% (without appropriate treatment) and in those who also breastfeed 35%.

8. Pathophysiology
HIV produces cellular immune deficiency characterized by the depletion of helper T lymphocytes (CD4+ cells). The loss of CD4+ cells results in the development of opportunistic infections and neoplastic processes.

9. Timeline of untreated HIV-infection.
From Wikipedia, based on an original from Pantaleo et al (1993).

10. Classification

11. Stages of HIV-infection
Incubation period (2 wks – 6 mth);
Primary infection (2-4 weeks);
Latency (2 wks – 20 yrs);
AIDS.

12. Primary infection Symptoms: Fever Fatigue Lymphadenopathy Pharyngitis
Maculopapular rash
Myalgia/arthralgia
Anorexia
Mucocutaneous ulceration
Headache, retroorbital pain
Neurologic symptoms (e.g., aseptic meningitis, radiculitis, myelitis, cranial nerve palsies)

13. WHO clinical staging of established HIV infection
HIV-associated symptoms
WHO clinical stage
Asymptomatic 1
Mild symptoms 2
Advanced symptoms 3
Severe symptoms 4

14. WHO clinical staging for children
Clinical stage 1
Asymptomatic
Persistent generalized lymphadenopathy
Clinical stage 2
Unexplained persistent hepatosplenomegaly
Papular pruritic eruptions
Fungal nail infection
Angular cheilitis
Lineal gingival erythema
Extensive wart virus infection
Extensive molluscum contagiosum
Recurrent oral ulcerations
Unexplained persistent parotid enlargement
Herpes zoster
Recurrent or chronic upper respiratory tract infections

15. WHO clinical staging for children (continuation)
Clinical stage 3
Unexplainedi moderate malnutrition or wasting not adequately responding to standard therapy
Unexplained persistent diarrhoea (14 days or more)
Unexplained persistent fever (above 37.5°C intermittent or constant,
for longer than one month)
Persistent oral candidiasis (after first 6–8 weeks of life)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis or periodontitis
Lymph node tuberculosis
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
Symptomatic lymphoid interstitial pneumonitis
Chronic HIV-associated lung disease including brochiectasis
Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 109 per litre)
and or chronic thrombocytopaenia (<50 × 109 per litre)

16. WHO clinical staging for children (continuation)
Clinical stage 4
Unexplained severe wasting
Pneumocystis pneumonia
Recurrent severe bacterial infections
Chronic herpes simplex infection and Cytomegalovirus infection
Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
Extrapulmonary tuberculosis and Disseminated non-tuberculous mycobacterial infection
Kaposi sarcoma
Central nervous system toxoplasmosis
Extrapulmonary cryptococcosis (including meningitis)
Disseminated endemic mycosis (coccidiomycosis or histoplasmosis)
Chronic cryptosporidiosis, isosporiasis
Cerebral or B-cell non-Hodgkin lymphoma
HIV encephalopathy and progressive multifocal leukoencephalopathy
Symptomatic HIV-associated nephropathy or HIV-associated cardiomyopathy

17. Stage of immunosupression associated with HIV
WHO immunological staging (2006)
Stage of immunosupression associated with HIV
Age-related CD4 values
<11
months
(% CD4+)
12-35 months
36-59 months
>5 years
(absolute
number
per mm3 or
%CD4+)
Absent or insignificant
>35
>30
>25
>500
Mild
30-35
25-30
20-25
Moderate
15-20
Severe
<25
<20
<15
<200 or
<15%

18. Who should be tested for HIV?

19. HIV testing should be also routinely offered and recommended to the following patients:
all patients presenting for healthcare where HIV, including primary HIV infection, enters the differential diagnosis (see table of indicator diseases and section on primary HIV infection)
all patients diagnosed with a sexually transmitted infection
all sexual partners of men and women known to be HIV positive
all men who have disclosed sexual contact with other men
all female sexual contacts of men who have sex with men
all patients reporting a history of injecting drug use
all men and women known to be from a country of high HIV prevalence (>1%*)
all men and women who report sexual contact abroad or in the UK with individuals from countries of high HIV prevalence.

20. Clinical indicator diseases for pediatric HIV infection
ENT Chronic parotitis; Recurrent and/or troublesome ear infections
Oral Recurrent oral candidiasis; Poor dental hygiene
Respiratory Pneumocystis Recurrent bacterial pneumonia; CMV pneumonitis; Lymphoid interstitial pneumonitis; Tuberculosis; Bronchiectasis
Neurology HIV encephalopathy; Developmental delay; meningitis or encephalitis; Childhood stroke
Dermatology Kaposi’s sarcoma Severe or recalcitrant dermatitis; Multidermatomal or recurrent herpes zoster; Recurrent fungal infections; Extensive warts or molluscum contagiosum
Gastroenterology Wasting syndrome; Unexplained persistent hepatosplenomegaly; Persistent cryptosporidiosis; Hepatitis B infection; Hepatitis C infection
Oncology Lymphoma; Kaposi’s sarcoma
Haematology Any unexplained blood dyscrasia including: thrombocytopenia, neutropenia, lymphopenia
Ophthalmology Cytomegalovirus retinitis; Any unexplained retinopathy
Other Recurrent bacterial infections (e.g. meningitis, sepsis, osteomyelitis, pneumonia etc.); Pyrexia of unknown origin

21. Etiologic spectrum of opportunistic infections
Bacterial infections
Mycobacterium tuberculosis
Mycobacterium avium complex
Salmonella, Campylobacter, E. coli, Pseudomonas, Kledsiella.
Staphylococcus, Streptococcus, Hemophillus pneumoniae
Mycotic infections
Candida, Aspergillus
Cryptococcus neoformans, Pneumocystis carinii
Histoplasma capsulatum, Coccidioides immitis
Protozoan infection
Toxoplasma gondii
Cryptosporidium
Isospora belli, Microsporidia
Viral infection
Herpes viruses: HSV, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8,
Papovaviruses 21

22. Kaposi's sarcoma

23. Herpes zoster 23

24. Candidiasis 24

25. Pneumocystis pneumonia

26. Which test to use?

27. HIV-infection examination
Serological test for HIV-antibodies, Enzyme Immunoassay (EIA)
Immunoblot analyses (Western blot)
PCR (proviral DNA), Viral load
Viral antigens (p24 with EIA) viral RNA detection
For immunodeficiency stage - level of CD4 cells
In case of positive EIA –make it twice, confirmation by Western blot.
Also other methods are available: looking for viral antigens (p24 with EIA), viral RNA or whole virus detection-using PCR tests. Could be usefull in early stages of the disease when antibodies and not present yet and also in terminal stages when antibody level is to low. 27

28. Who should be treated?

29. Age related indication
Indication for Anti Retroviral Treatment (ART)
Clinical stage
Level of CD4+ -Т-lymphocytes
Age related indication
<12 months
>12 months IV
Any
Start ART
III
Immunosupression
Start ART depend on grade of immusupression and opportunistic diseases II
Start ART depend on grade of immusupression І

30. Goal of ART
Virologic criteria: inhibition of viral replication (decreasing viral load)
Immunologic criteria: restoring and preserving of immune response
Clinical criteria: decline incidence of opportunistic infections
Epidemiologic criteria: decreasing infection transmission
Social criteria: life quality improvement, decreasing mortality rate, increasing life span

31. Which medication to use?

32. ARV drugs
NRTI - Nucleoside Reverse Transcriptase Inhibitors (e.g. abacavir, tenofovir)
NNRTI - Non-nucleoside Reverse Transcriptase Inhibitors (e.g. efavirenz, nevirapine)
PI - Protease Inhibitors (e.g. lopinavir, sequinavir)
EFI - Entry and Fusion Inhibitors (e.g. enfuvirtide)
II - Integrase Inhibitors (e.g. raltegravir)

33. Treatment regimes in children
1 NNRTI + 2 NRTI or
1 PI + 2 NRTI
Duration - lifelong

34. How to prevent HIV on individual level?

35. Prevention of sexual transmission
Reduction in number of sexual partners
Using barrier contraception
Treatment of concurrent sexually transmitted diseases (STDs)
Testing of self and partner for HIV and other STDs

36. Prevention of vertical transmission
Maternal testing
Effective control of maternal infection
Prenatal antiviral therapy and treatment of mother and infant during labor, delivery, and the neonatal period
Cesarean delivery
Avoidance of breastfeeding

37. Postexposure prophylaxis (occupational)
Percutaneous superficial injury or small volume splash:
Known HIV status – antiretroviral prophylaxis
Unknown HIV status or unknown source – prophylaxis not recommended
Percutaneous deep injury or large volume splash:
Known HIV status or HIV risk factor – antiretroviral prophylaxis