Transcript HIV infection in children

O.O.Bogomolets National Medical University
department of pediatric infection diseases
HIV infection in children
Yevtushenko V.
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.
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
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 230 000 children.
Adults and children estimated to be living
with HIV, 2007
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.
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%.
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.
Timeline of untreated HIV-infection.
From Wikipedia, based on an original from Pantaleo et al (1993).
Classification
Stages of HIV-infection
•
•
•
•
Incubation period (2 wks – 6 mth);
Primary infection (2-4 weeks);
Latency (2 wks – 20 yrs);
AIDS.
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)
WHO clinical staging of established
HIV infection
HIV-associated symptoms
WHO clinical stage
Asymptomatic
1
Mild symptoms
2
Advanced symptoms
3
Severe symptoms
4
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
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)
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
WHO immunological staging (2006)
Age-related CD4 values
Stage of
immunosupression
associated with HIV
<11
months
(% CD4+)
12-35
months
(% CD4+)
36-59
months
(% CD4+)
>5 years
(absolute
number
per mm3 or
%CD4+)
Mild
>35
30-35
>30
25-30
>25
20-25
>500
350-499
Moderate
25-30
20-25
15-20
<25
<20
<15
200-349
<200 or
<15%
Absent or insignificant
Severe
Who should be tested for HIV?
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.
Clinical indicator diseases for pediatric HIV
infection
ENT
Oral
Respiratory
Chronic parotitis; Recurrent and/or troublesome ear infections
Recurrent oral candidiasis; Poor dental hygiene
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
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
Kaposi's sarcoma
Herpes zoster
Candidiasis
Pneumocystis pneumonia
Which test to use?
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
Who should be treated?
Indication for Anti Retroviral Treatment (ART)
Clinical stage
IV
Level of CD4+ -Тlymphocytes
Age related indication
<12 months
>12 months
Any
Start ART
Start ART
Any
Start ART
III
Immunosupression
Start ART
Start ART depend
on grade of
immusupression
and opportunistic
diseases
II
Immunosupression
Start ART depend on grade of
immusupression
І
Immunosupression
Start ART depend on grade of
immusupression
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
Which medication to use?
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)
Treatment regimes in children
• 1 NNRTI + 2 NRTI
or
• 1 PI + 2 NRTI
Duration - lifelong
How to prevent HIV on individual
level?
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
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
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
Unknown HIV status or unknown source – prophylaxis not
recommended