1 HIV/AIDS in children. 2 Plan of the lecture The etiology of HIV infection, history of the HIV...

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HIV/AIDS in children

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Plan of the lecture

The etiology of HIV infection, history of the HIV discovery

HIV infection epidemiology, pathogenesis HIV infection diagnostic criteria HIV infection Antiretroviral Therapy HIV infection prevention

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HIV: Human Immunedefficiency Virus

a retrovirus, its genetic material, RNA, while replicating change the structure of host cell DNA

AIDS: Aquired Immune Defficiency Syndrome

HIV-infection AIDS

8-10 years in average* *without treatment

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HIV infection - a chronic infectious disease that develops because of infection with human immunodeficiency virus (HIV) and is characterized by progressive immune system

damage

AIDS - a terminal (final) 4th stage of the HIV infection course as the result of the human immune system destruction by the virus (HIV), and loss of human capacity to resist infections and diseases

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History of HIV discovery History of HIV discovery Spring 1981 - + 5 patients with malignant pneumocystis pneumonia

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History of HIV discoveryHistory of HIV discovery winter 1980-81 -- first patients with Kaposi sarcoma, malignant form in the United States

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RR. . GALLOGALLO LL. . MontMontoonnaeae

They They had had opened HIVopened HIV

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Human immunodeficiency virus 109 new viruses

Appears every day reverse

transcriptase makes “errors" at each transcription

there significant number mutations due large number of errors, but on undetectable level

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Etiology

HIV - Т- lymphotropic retrovirus of ІІІ type RNA-containing, cells-targets – DNA-соntaining (helpers

T-lymphocytes) Enzymes: reverse transcriptase (revertase), protease Specific markers – p24, gp41, gp120, gp160 Genome of the virus include 3 structure genes (as all

retroviruses) and 6 regulatory genes (increase replication, activate of virus protein structure synthesis)

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HIV BIOLOGICAL CHARACTERISTICS - HIGH genetic variability (up to 104 -105

mutations / gene / every replication cycle, predominantly in the gene gp120)

Resistance of HIV in an infected organism - Rapid development of drug resistance - Modified tropism of HIV at different stages

of disease - Difficulty in creating an effective vaccine

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Stability of the virus in the Environment When drying the cell cultures will kill the virus at t˚ +23

+27 ˚C for 3-7 days. In liquid at a temperature of +23-27 C - within 15 days, In the blood for transfusion is going through the years,

and in the frozen serum - activity persists up to 10 years.

HIV dies quickly when using disinfectants, UV radiation, when heated above 56 C loses activity after 30 minutes.

HIV loses activity under the influence of protective enzymes of saliva and sweat.

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Epidemiology Source – sick and carrier (contagious during all life) Mеchanism of transmission – contact (wound), vertical Ways of transmission: natural: sexual (homosexuals – 1-3 %, females – 0.6 %,

males – 0.09 %) vertical (transplacentar – 15-20 %, childbirth – 50-70 %,

during breast feeding – 20-30 %) artificial: parenteral manipulations and drug using – 30

%, blood recipients – 100 %, transplantation of organs and tissues, artificial abortion – 100 %

professional: infection of medical personal – 0.1-0.4 %. Intrahospital outbreaks.

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WHAT   BE   FOR   TRANSFER   HIV?

HIV +

HIV

Ways of transmission: - sexual,

-Through the blood, - From mother to child

HIV-

Factors transfer (Biological fluids with

high HIV-content)

sperm Vaginal -

secret blood milk

When  absence although one of these factors the chain will torn and infection is not developed 

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Estimated risk of transmission HIV from mother to child (in the absence of any interventions)

During pregnancy, 5-10% During childbirth 10-20% When breastfed 5-20%

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HIV is not transmitted:

When insect bites (mosquitoes, fleas, lice, beetles, flies, etc.)

With saliva, sweat, urine, feces, sputum, discharge from the nose, tears, vomitus (if there is no visible admixture of blood)

Household contact

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Transmission has not been proved during puncture Cerebrospinal Synovial Pleural Peritoneal Pericardial Amniotic

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Biological fluids, which contacted you may be infected HIV:

Blood and any liquid with a visible admixture of blood

Sperm Vaginal Discharge Culture containing HIV

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Treated with care require:

any biological fluid, if it is difficult to determine what kind of fluid

Any excised (or deleted by other means, in vivo or post-mortem) human tissues and organs

tissues and organs of experimental animals infected with blood-borne infections;

any cuts of unknown origin.

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Trans-dermal contact Needlesticks cut with a sharp object

Contact with biological materials on mucous membranes or broken skin

Contact intact skin with blood, biological tissues or fluids for a long time or over a large area

Contacts associated with the risk of infection:

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Assessment of infection risk contact with HIV-infected blood through the

damaged skin, 0,3% (0,2 - 0,5%) getting blood on the mucous membranes -

0,09% (0,006-0,5%) contact with intact skin - the risk is not

detected contact with body fluids - the risk is not

detected

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The risk of transmission of the virus in trauma with a sharp instrument contaminated with body fluids of an infected patient

Patient Risk

HIV + 0,3%

HBsAg+

HBeAg+

3%

30%Hepatitis C 2%* Невакцинированные медработники

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Ways of infection when professionally contact

Ways of infection when professionally contact

Інфікування при пораненні 90

Інфікування через слизові 10

90%10%

From: CDC. MMWR 1998;47:No. RR-7.

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Pathogenesis of HIV infection in humans Infection occurs through close contact with blood or

other body fluids containing the virus in sufficient quantities for infection (semen, vaginal secretions, breast milk)

In the penetration of the virus in the body involved mucosal dendritic cells

The virus rapidly infects activated CD4 lymphocytes near the gate of infection and reaches with them the regional lymph nodes

Following this, HIV is spread through the body with blood and lymph

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Pathogenesis of HIV infection The virus is detected in the blood and lymph nodes, in

long-living lymphocytes it is contained in a latent form, which makes it impossible to completely eliminate.

Persistent failure of the lymphatic system occurs within 48 hours In contact with infected blood or other body fluids should be as

soon as possible to take preventive measures (optimal in the first hours after contact)

For some groups of patients it is characterized by depression of the immune system and a more rapid progression of infection. These include:

Infants Individuals with defects in the immune system

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The life cycle of HIV and a target for drugs

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HIV and the immune system HIV uses mostly CD 4 cells to reproduce CD 4 cells - contain CD 4 receptors on their

surface CD 4 receptors are located on the surface of

many cells, but mainly on the T 4 lymphocytes (T helper)

The shell of the virus contains a molecule that helps him connect to the CD4 receptor and to penetrate into the cell

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A “Window" Period

АТ

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HIV and the immune system"Window" Period

This is the time needed to accumulate in the body a sufficient number of antibodies to HIV, which is determined by laboratory

tests

(3 months - in 99%)

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DEVELOPMENT OF HIV INFECTION

Stages:

Acute viral infection

The latent period of asymptomatic carriers

HIV infection (4th stage - AIDS)

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Development of the diseaseDevelopment of the disease 2004 WHO Classification2004 WHO Classification

Clinical stage I

Asymptomatic Generalized lymphadenopathy

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Development of the diseaseDevelopment of the disease 2004 WHO Classification2004 WHO Classification

Clinical stage II

Weight loss is less than 10% of the original

Mild skin and mucous damages Shingles (herpes Zoster) Recurrent upper respiratory tract infection

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Herpetic stomatitis (Canker Sore)

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Herpes simplex

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Rerccurent Herpes labialis (Cold Sore)

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Herpes Zoster

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Development of the diseaseDevelopment of the disease 2004 WHO Classification2004 WHO Classification

Clinical stage III

Weight loss is more than 10% of the original Diarrhea of unknown etiology Prolonged fever of unknown etiology Oral Candidiasis Oral hairy leukoplakia Pulmonary tuberculosis Serious bacterial infection

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Oral Candidiasis (thrush)

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Oral Candidiasis (thrush)

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Leukoplakia

Oral hairy leukoplakia

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Development of the diseaseDevelopment of the disease 2004 WHO Classification2004 WHO Classification

Clinical stage IV (AIDS) HIV cachexia PCP Toxoplasmosis Kaposi’s sarcoma Lymphoma Other AIDS indicator disease

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Kaposi sarcoma

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Mouth cancer

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Condyloma acuminata (Human Papylomavirus infection)

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Lichen planus

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Indicators that determine the stage Indicators that determine the stage

of HIV infection:of HIV infection: Clinical

Immunological Virological

Virus load

Number   and % CD4/8

Total   number  of lymphocytes

Opportunistic infections and AIDS - Indicator diseases

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Examples of the diagnosis by WHO classification: HIV infection, the second clinical stage,

without significant immunosuppression HIV infection, the fourth clinical stage,

severe immunosuppression.

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Opportunistic infections

HIV slowly destroys CD 4 cells during many years of infection

When the number of CD 4 cells decreases germs of infectious diseases can easily penetrate into the body, causing the development of opportunistic infections (germs that do not cause pathological process in people with normal immunity)

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Laboratory studies Serological methods for diagnosis of HIV

infection. ELISA (routine serological test). Immune blot method (Western blot). Determination of antigen-R24. Determination of R24-

antigen in serum implies the presence of HIV in the body. It appears in the blood, as in the early stages, and in progression of HIV infection.

Molecular genetic and virological research methods

HIV DNA PCR HIV RNA PCR Getting HIV culture

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Diagnosis of HIV-infected child under 18 months: age - under 18 months + antibodies to HIV determined in serum (ELISA

and immune blot) or a child was born by HIV-infected women +

child has two positive results, done by one of the following methods: PCR DNA a culture of HIV definition of R24 antigen.

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Diagnosis of HIV-infected child older than 18 months: age - 18 months and older + antibodies to HIV determined in serum (ELISA

and immune blot) + a child was born by HIV-infected women or the child received blood or the child received

the virus by other means (including sexually).

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Diagnosis of HIV perinatal contact (status is uncertain): age - under 18 months + antibodies to HIV determined in serum

(ELISA and immune blot) or a child was born by HIV-infected women.

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HAART: Highly active Antiretroviral Therapy (or triple combination therapy)

The only effective way to suppress the virus

Use one or two drugs leads to the fact that the virus becomes resistant (resistance)

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Механизм действия АРВпрепаратов

ОТ

ПРОВИРУС

ПРОТЕИНЫРНК

РНК

ОТ

РНК

РНК

ДНК

ДНК

ДНК

Протеаза

Обратнаятранскриптаза

Фузион

Интеграза

ИнгибиторыпротеазыSQVRTVIDVNFVLPV

1 НуклеозидныеингибиторыобратнойтранскриптазыZDV, ddI,d4T, 3TC, ABC,TDF, 2 Не-нуклеозидныеингибиторыобратнойтранскриптазыNVP, EFV

ИнгибиторыслиянияEFV (T20)

РНК

от

РНК

ДНКот

ДНК

ДНК ПРОВИРУС

РНК

РНК

ПРОТЕИНЫ

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NNRTI

’’8787 ’’9191 ’’9292 ’’9494 ’’9595 ’’9696 ’’9797 ’’9898 ’’9999 ‘‘0000’’8888 ’’8989 ’’9090

RTIRTI

PIPI

RetrovirRetrovir

NorvirNorvir

InviraseInvirase

CrixivanCrixivan

FortovaseFortovase

KaletraKaletraViraceptViracept

ZiagenZiagen

CombivirCombivir

VidexVidex

HividHivid

ZeritZerit

EpivirEpivir

TrizivirTrizivir

Rescriptor

SustivaViramune

’’0101

VireadViread

EmtrivaEmtriva

FuzeonFuzeon

ReyatazReyataz

‘‘0202 ‘‘0303’’9393

AgeneraseAgenerase

LexivaLexiva

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History   ARV   drugs From 1987 to 1995. To use the 4 ARV drug Class NRTIs. In second half of the 90 - x years started used NNRTI drugs. Since 1995 started application protease inhibitors (PI).

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Effects of ARV therapy

The purpose of ARV therapy: Improve the quality of life Prolong life

ARVs do not cure people of HIV infection Lifetime administration of drugs Commitment (attitude and punctuality

admission)

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Effects of ARV therapy

HIV ceases to be a death sentence for people

and becomes a "chronic" disease

which - subject to constant use of the drugs - you can live, learn, work, create a family, having children.

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Problems associated with ARV drugs

Limited access to ARV drugs Long-term (life), which requires strict regime of

time reception (commitment) - necessity of uninterrupted supply of ARV drugs

The presence of side effects that reduce quality of life of the patient

Difficulties with the quality monitoring of the patient and his viral load

Fear of disclosure of HIV status

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Benefits Benefits antiretroviral therapy antiretroviral therapy Ability to reduce viral load

Ability to reduce the risk of vertical transmission of HIV from mother to child

Ability to extend the life of a person with AIDS

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The first ART series schemes

recommended in Ukraine Schemes based on NRTI: 1 NNRTI + 2 NRTIPreference is recommended to:

EFV + AZT / ZTS

EFV + TDF * + FTC * (or ZTS)

Possible use, but not a full-fledged alternative: NVP + AZT / ZTS

Schemes based on PI: 1 PI + 2 NRTI

Preference is recommended to:

LPV / rtv + AZT / ZTS

LPV / rtv + TDF + FTC (or ZTS)

Possible use in case intolerance to LPV / rtv, but not a full-fledged alternative: NFV + AZT / ZTS

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Dosing regimens of antiretroviral drugs for adults

and adolescents Nucleoside / nucleotide reverse transcriptase inhibitors (NRTI)

Zidovudine (AZT) 300 mg 2 times a day

Stavudine (d4T) 40 mg 2 times a day (30 mg 2 times a day, with weight <60 kg)

Lamivudine (ZTS)

150 mg 2 times a day

Didanozine (ddI) 200 mg 2 times daily or 400 mg 1 per day (in the application of capsules)

(250 mg 1 per day, with weight <60 kg or reception in conjunction with TDF)

Abacavir (FAA) 300 mg 2 times a day

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Nucleoside / nucleotide reverse transcriptase inhibitors (NRTI)

Emtriсytabine (FTC) 200 mg 1 per day

Tenofovir (TDF) 300 mg 1 per day

Combination drug AZT / ZTS

300 mg/150 mg 2 times a day

Combination drug AZT / ZTS / ABC

300 mg/150 mg/300 mg 2 times a day

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Nonnucleoside reverse transcriptase inhibitors (NNRTI) Efavirence (EFV) 600 mg 1 per day (in

combination with rifampicin 800 mg 1 per day)

Nevirapine (NVP) 200 mg 1 time per day during the first 14 days

than - 200 mg 2 times a day

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Protease inhibitors (PI)

Lopinavir / ritonavir (LPV / rtv)

400 mg/100 mg 2 times a day (if granted in conjunction with ifavirentsom or Nevirapine, a dose increase to 533 mg/133 mg 2 times a day)

Nelfinavir (NFV) 1250 mg 2 times a day

Saquinavir / ritonavir (SQV / rtv)

1000 mg/100 mg 2 times a day

Atasanavire / ritonavir (ATV / rtv)

300 mg / 100 mg 1 per day

Fosamprenavir / ritonavir (FPV / rtv)

700 mg/100 mg 2 times daily or 1400 mg/200 mg 1 per day

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Other treatment Immune correction – interleukin-2 (roncoleukin), tactivin,

timalin, inerferons, immunofan, splenin, galavit, specific (monoclonal) antibodies, transplantation of thymus аnd bone marrow

Treatment of opportunistic infections protozoal – Trymetoprim/sulfametoxazolum,

pirimethamin/sulfamеthоxаzоlum, metronidazolum, pentamedinum; mycosis – amphotericin В, kеtоkоnаzоlum, flukonazolum; herpetic infection – acyclovir, valtrex, zovirax, interferon, laferon; CMV-infection – gancyclovir, foskarnet; bacterial – antibiotics – macrolids, fluorqinolons, karbapenems,

cephalosporins, aminoglycosides) Anti tumor remedies Pathogenetic and symptomatic therapy

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Vaccination schedule for children born by HIV

positive women, HIV infected and AIDS patients BCG Contraindicated

DPT / DT Ply on the calendar

Hepatitis B Ply on the calendar

Hib Ply on the calendar

MMR Ply on the calendar

Inactivated (IPV) Ply on the calendar

Oral, live (OPV) Contraindicated

Rabies Only postcontact prevention

Influenza Every autumn, repeated annually

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Prevention of HIV Transmission

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Approaches to HIV prevention

Removing risk Reducing risk

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Mandatory testing of blood and special processing of blood products.

Prevention of infection in health care and beauty parlors (tools for injection and manipulation by contact with blood).

Prevention of occupational infection with HIV (medical personnel, etc.)

Methods of parenteral infection prevention

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Fighting HIV infection in health care Use of disposable instruments Handwashing Use of personal protective equipment: gloves,

goggles, apron, and shoe covers Organization of activities in case of emergency When drawing blood and conducting laboratory

and diagnostic studies of blood and other body fluids of any patient should be treated as potentially dangerous in terms of HIV infection

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Guidelines reduce the risk of HIV

transmission from mother to child Antiretroviral prophylaxis for mother and

child Planned (elective) Caesarean section Artificial feeding Also recommended:

Prevention or treatment by STDs Noninvasive procedures

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Post-Exposure Prophylaxis of HIV infection

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First aid for exposure to HIV through injury

Immediately! Wash the damaged area with soap and water Rinse it under running water wash the surface by disinfectant or gel for hand washing

NOT! alcochol Iodine Squeezing or rubbing Suck blood

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First aid for exposure to HIV through spraying

Immediately! Wash the damaged area with soap and water wash the surface by disinfectant or gel for hand washing 2-4% chlorhexedin gluconate solution Rinse eyes with water

NOT! alcochol Iodine bandage

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PEP (Post Exposure Prevention) . Protocol. ARVs

(If the result of HIV testing in an employee-negative, and the patient's positive): A. Beginning in the early hours after exposure (Required no

later than the first 72 hours). B. Assign triple ART course for 4 weeks: Two drugs - a combination of zidovudine and lamivudine: Zidovudine - 300 mg every 12 hours, and lamivudine - 150 mg orally every 12 hours

The third drug: lopinavir / ritonavir - 400/100 mg orally every 12 hours (the

drug of first choice) Alternative PI but less preferred:

saquinavir / ritonavir - 1000/100 mg orally 2 times a day.

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Epidemic situation

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Statistics 6-7 thousand young people infected with HIV every day The rate of infection in the world 4.5 people / minute 50% of new infections - young people aged 15-24 years 50% of the total number of PLHIV - Women 13.1 million children worldwide have been orphaned by

HIV, to 2010, the number of orphans will reach 25 million man

At the beginning of the HIV epidemic was assumed that the victims of the epidemic by 2006 will be 1.7 million people

95% of People Living with HIV live in developing countries

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Characteristics of the epidemic Struck the younger generation. In the world

- more than one-third of people aged 15 to 24 years living with HIV / AIDS

Most people do not know about that are infected with this virus

Many millions know nothing or almost nothing about HIV to protect themselves from infection

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Level   transfer   HIV   from   mother   to   child (%) for   Ukraine

40%27%

10,00 %

10,00 %

8.20%

7.70%

7,00 %

0% 5% 10% 15% 20% 25% 30% 35% 40%

2000

2001

2002

2003

2004

2005

2006

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Thank you for your attention!