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negat hiv e AIDS HIV and AIDS H uman immunodeficiency virus infection and acquired immune deficiency syndrome is a spectrum of conditions caused by infection with the HIV virus ID: 913768

virus hiv aids infection hiv virus infection aids cells blood risk patients cell inhibitors tests reverse dna cd4 surgery

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Slide1

#Stay negathive -AIDS

Slide2

HIV and AIDSHuman immunodeficiency virus infection and acquired immune deficiency syndrome is a spectrum of conditions caused by infection with the HIV virus .

A syndrome in which there is severe loss of the body’s cellular immunity, greatly lowering the resistance to infections and malignancy.

Slide3

History of HIV and AIDS

Slide4

IncidenceSTD:- 2.5% Migrants:-3.61%Trucker:-2.51%IDU:-9.2%MSM:-7.4%FSW:-4.9%

Trends of HIV infection indicates that it is spreading in two ways :-

Urban to rural population

HRG to general population

HIV BURDEN IN INDIA:

Adult prevalence – 0.31%Age group -15-49 yrs( 88.55%)In north eastern states principle cause of HIV epidemic is Injecting drug usersTuberculosis is most common infectious cause of death in HIV infected people

Slide5

Human Immunodeficiency Virus In 1986, The international committee on Virus Nomenclature decided on the generic name of the causative virus as the Human Immunodeficiency virus. Found in body fluids-

Blood,semen,vaginal,cervical

secretions

Breast milk.

HIV, the etiological agent of AIDS, belongs to Lentivirus Subgroup of

the

retroviridae family. This family of viruses is known for latency, persistent viremia, infection of the nervous system and weak host immune responses.

Slide6

Human Immunodeficiency Virus HIV has high affinity for CD 4 T Lymphocytes and Monocytes. HIV binds to CD4 cells and becomes internalized. The virus replicates itself by generating a DNA copy by reverse transcriptase. Viral DNA becomes incorporated into the host DNA enabling further replication.

Slide7

Structural characterstics of HIV

Slide8

Slide9

Antigenic variations in HIV Based on molecular and antigenic differences , two types of HIV have been recognized. The original isolates of HIV and the related strains present all over the world belong to HIV type 1 The HIV strains, which react with HIV type 1 antiserum very weakly or not all have been termed as HIV type 2.It has 40% genetic similarity and is more closely related to Simian immunodeficiency virus than to HIV-1 It can cause AIDS but it is less pathogenic and is less common.

HIV is highly mutable virus and exhibits frequent antigenic variations as well as differences in other features such as nucleotide sequences, cell tropism, growth characteristics and

cytopathology

.

The differences may be between isolates of HIV from different races or persons but also between sequential isolates from the same person, and even between those obtained from different sites of the same person at the same time. This great variability is believed to be due to error prone nature of reverse transcription.

Slide10

Sub types of HIV -1

Slide11

How do you get HIV?

Slide12

Slide13

Slide14

Pathogenesis Targets of HIV- Infection is transmitted when virus enters the blood or tissues of a person and comes in to contact with a suitable host cell, principally the CD4 Lymphocytes. The virus may infect any cell bearing the CD4 antigen on the surface. Primarily these are the CD4 + helper T lymphocytes.

Some other immune cells possessing CD4 antigens are also susceptible to infection ,like B lymphocytes,

monocytes

and macrophages including specialized macrophages such as Alveolar macrophages in the lungs and

langerhan

cells in the dermis. Glial cells and microglia cells are also susceptible.

Slide15

Immune deficiency in HIV infectionDecreased number of T helper cells

Decreased activity of

monocytes

& macrophages

Decreased activity of B lymphocytes

Decreased cell mediated immune response

Decreased activity of NK cells.

Slide16

INCUBATION PERIOD The incubation period is from HIV infection till development of AIDS. It is from few months to 10 years or even more. However it is estimated that 75% of people infected with HIV will develop

AIDS at the end of 10 years.

Slide17

Clinical ManifestationsAcute HIV infection.2.Asymptomatic or Latent Infection.3.Persistent generalized Lymphadenopathy (PGL)

4.AIDS related complex.

5.Full blown AIDS( Last stage).

Slide18

Acute infection: The initial period following the contraction of HIV is called as acute HIV/ Primary HIV or acute retroviral syndrome. A flu like illness with fever, sore throat,

headache, tiredness, skin rashes and

enlarged lymph nodes in the neck within

several days to weeks after exposure to virus.

The test for HIV antibodies appears negative. while HIV antigenemia (p24 antigen) and viral nucleic acids can be demonstrated at the beginning

of the phase.

This phase is also called as window period or phase of sero conversion. Some patients do not develop symptoms after they first get infected with HIV.

Slide19

2.Asymptomatic or Latent infection The initial symptoms are followed by a stage called Asymptomatic or latent infectionTypically there are few or no symptoms at first, near the end of this stage many people experience fever, weight loss, GIT problems and muscle pains, Generalized Lymphadenopathy, characterized by non painful enlargement of more than one group of lymph nodes for 3-6 months.

This state may last from few months to more than 10 years.

During this phase the virus continues to multiply actively infects, and kills the cells of the

immune system.

CD4 count is greater than 500 per

microlitre. The patients show positive antibody tests during this phase.

About 5-10% of the infected appear to escape clinical AIDS for 15 years or more and are

known as ‘ long term survivors’ or ‘long term non progressors’.

Slide20

3.Persistent generalized lymphadenopathy (PGL) This has been defined by presence of enlarged lymph nodes, atleast 1cm in

diameter ,in two or more non contiguous

extra inguinal sites, that persist for

atleast

three months, in the absence of any current illness or medication that may cause lymphadenopathy. CD4 count is less than 500 per

microlitre

These are diagnostic of HIV when blood tests are positive for antibodies.

Slide21

4. AIDS related complex. The patients present with weight loss-of more than 10% of body weight, persistent fever, diarrhoea, generalized fatigue and signs of other opportunistic infections may be apparent. CD4 count is less than 350 per microlitre.

The opportunistic infections are oral

candidiasis

, herpes

zooster

, salmonellosis or tuberculosis and hairy cell leucoplakia.

Slide22

5. Full blown AIDS This is the end stage disease representing the irreversible break down of immune defense mechanisms. CD4 count is less than 200 per microlitre. In addition to the opportunistic infections the patient may develop primary CNS Lymphomas And progressive multifocal

leuko

encephalopathy, dementia and other neurological

abnormilities

.

Kaposi sarcoma, pneumocystis pneumonia and candidiasis of oesophagus, trachea are almost always observed in a majority of patients.

Slide23

AIDS in childrenInfants who are seropositive at 18months are infectedInfants progress to AIDS more rapildy usually in 3 years.Transmission is usually

perinatal

100% are HIV positive at birth

THREE STAGES-

Stage 1-Asymptomatic,Generalized

lymphadenopathyStage 2-Chronic diarrhoea,weight

loss,

fever,bacterial infections.Stage 3-Oppotunistic infections,Failure to thrive, malignancy,septicaemia,meningitis

Slide24

DiagnosisNon specific tests and radiological tests- a) Total leukocyte and lymphocyte count - to demonstrate leucopenia and lymphopenia. The lymphocytic count is usually below 2000/mm

3

b) T cell subset Assays- Absolute CD4+ cell count is less than 200/L, T4 T8 ratio is reversed,

CD 4cells are decreased.

c) Full blood count ,Platelet count shows Thrombocytopenia. d) IgA and IgG levels are raised.

e) Diminished cell mediated immunity as indicated by skin tests.

f) Lymph node biopsy shows profound abnormalities. g) Serum, liver and renal function h) Fasting serum lipid profile. i) Fasting blood glucose. j)Toxoplasmosis serology , syphillis serology, screening for other sexually transmitted infections.

k)Cervical cytology, chest x-ray, CT scan, MRI, EEG

Slide25

2) Specific tests for HIV infection- *HIV antigen*Antibodies*Viral nucleic acids or other components*Isolation of virus.

Slide26

HIV antigen and antibody test

Slide27

Screening testsELISA- First generation- whole viral lysates Second generation- glycopeptides Third generation- synthetic peptide Fourth generation- antigen + antibody

Significance of ELISA-

Antibody can be detected in a majority of individuals within 6-12 weeks after infection using the generation of assays.

It can be detected within 3-4 weeks when using the newer third generation ELISA.

Due to their ability to detect p24 antigen, the fourth generation ELISA can be of value in detecting early infection.

Slide28

Supplemental testsWestern blot testIndirect immunoflorescence testRadio Immunoprecipitation assayRapid tests

a)Dot Blot assay

b) Particle agglutination tests

c)HIV spot and comb test

d)

Fluorimetric micro particle technologies.

Slide29

PCR- In this the target HIV RNA or proviral DNA is amplified enzymatically invitro by chemical reaction.

It is an extremely sensitive assay because a single copy of

proviral

DNA can be amplified.

Qualitative PCR is useful for diagnostic purposes.

Three different techniques namely- RT-PCR, nucleic acid sequence based amplification (NASBA) And branched DNA ( b-DNA) assay have been employed.

Slide30

Virus isolation Virus isolation is accompalished by the co cultivation of the patient’s lymphocytes with fresh peripheral blood cells of healthy donors or with suitable culture lines such as T lymphomas. The presence of the virus can be confirmed by reverse transcriptase assays, serological tests, or by changes in growth pattern of the indicator cells. Virus isolation is tedious and time consuming and successful in only 70-90% of cases.

Therefore virus isolation is mainly used for the characterization of the virus.

Slide31

Other tests-Oral fluids ( saliva).-Urine tests.

Slide32

ManagementImmunotherapy.Anti-HIV drugs.Psychosocial counselingNutritious diet.

Prevention

Avoidance of alcohol and smoking

Abstinence

Using condomsReducing number of sexual contacts.

Slide33

Immunotherapy- Immunotherapy is transfusion based treatment designed to replace lost immunoglobulins needed to fight HIV infection , to provide cellular factors such as interlukins (IL-2) or to introduce selected or altered immune cells to attack cells harboring the virus.

The results of trials using this latter approach however have been inconclusive, and no group has yet shown a survival benefit.

Slide34

Anti HIV drug treatmentReverse transcriptase inhibitors- They act at the pre – integration stage – before the viral RNA has been converted to DNA and enters the host cell nucleus to integrate into the cell chromosome. These drugs block the reverse transcription of viral RNA into viral DNA. There are two types of reverse transcriptase inhibitors, both of which accomplish the same objective: nucleoside and nucleotide analogues , and non-nucleoside reverse transcriptase inhibitors.

Slide35

a) Nucleoside analogues-The most effective antiretroviral drugs introduced in 1987. They act by mimicking nucleic acids normally incorporated into viral DNA.They interfere with reverse transcriptase and thus prevent infection.Nucleotide analogues have the same action but are based around different sugar.

Ex:

Zidovudine

( AZT) (250-300mg

b.i.d

), didanosine( 400mg once daily >60kgs), Stavudine( 40 mg twice daily) etc.

Slide36

b)Non- Nucleoside reverse transcriptase inhibitors-Directly inhibit reverse transcription and unlike nucleoside analogues.Ex: Nevirapine,( 200 mg once daily and Delavirdine

.(400mg thrice daily).

Slide37

Protease inhibitors- Protease inhibitors block HIV replication after integration. These drugs inhibit the function of the protease needed to process the ‘ gag –pol’ polypeptide into proteins. Since protease inhibitors act after integration, they can obstruct infectious HIV production in both acutely and chronically infected T cells and macrophages.

Saquinavir

(1000 mg daily),

Ritonavir

( 600mg twice daily), Indinavir (800mg twice daily) and Nelfinavir(1250mg twice daily) are the licensed protease inhibitors used in the clinical practice.

Slide38

Combination treatment Reverse transcriptase inhibitors and protease inhibitors are used in combination and has shown more effect than monotherapy in impeding the spread of HIV in the body and reducing viral loads. This combination of two reverse transcriptase inhibitors one of which is a thymidine analogue and a protease inhibitor blocks infection both before and after integration and in both activated and resting T cells.

This combinational therapy is termed as highly active anti- retroviral therapy (HAART)

Slide39

Management of HIV in pregnancy- Starts at 12-14 weeks of pregnancy and continue during delivery. Zidovudine is the drug of choice with baby receiving for 6 weeks postpartum. Women who do not need treatment for themselves should be prescribed a short course of antiretroviral therapy initiated between 22 and 28 weeks of pregnancy to reduce vertical transmission.

Efavirenz

is contraindicated in pregnancy.

ZDV regimen

Antepartum- ZDV 300mg bid

Intrapartum

-Iv dose of2mg/kg first hour followed by1mg/kg till delivery Post partum-ZDV syrup at 2mg/kg q6h to new born.

Slide40

Management in children with HIV Lopanavir16mg/kg/ritronavir4mg/kg in infants < 3years ( 300mg/kg) ( 75mg) in >12months

Doliutegravir

(35mg/day) + 2NRTI <12 years

Slide41

Approaches to HIV vaccinea)Preventive vaccineb)Perinatal vaccinec)Therapeutic vaccineTypes-Live attenuated vaccine-Inactivated vaccine-Subunit vaccine

-Synthetic peptide vaccine

-DNA vaccines

-Recombinant Vector vaccines

Slide42

Development of vaccine HIV can mutate rapidly, thus it is not possible to design antibodies against all antigens. Antibody alone is not sufficient, cell mediated immunity may also be necessary. Virus enters the body not as free virions but also as infected cells, in which the virus or the provirus is protected against antibody or cell mediated

lysis

.

Virus readily establishes life long latent infection hiding from antibodies.

Slide43

Slide44

Differential diagnosis-Primary herpes simplex infection.Burkitt lymphomaMycobacterium avium complex (MAC)

Slide45

Occupational risk from HIV-

Slide46

Risk of transmission to surgeons- The surgeons are regularly exposed to blood which is the most infective medium for HIV transmission. Incidence of accidental exposure to infected patients blood is 6.4% Risk is greater when there are more HIV particles in blood . materials- needle stick injury is 0.3% and other sharps.

Risk of transmission in surgery is 1 in 28000-50000 per hour of operations.

Risk is more when surgery lasts more than 3 hrs,> 300ml blood loss ,in intra-abdominal

and gynaecological surgeries.

Injuries like cut or sharp instrument penetration.

Contact of eyes, nose, mouth or broken skin with blood or other body fluids.

Slide47

Needle stick injuries-Passing of sharp instruments by handPrick while operatingDiscarding needleAdministration of injectionRecapping needleAfter IV cannula

removal

While administrating local anaesthesia

Prick while focusing microscope

Paracentesis

with 26 gauge needle.

Slide48

Surgery in the management of clinical problems of HIV infection--Lymphadenopathy-Immune deficiency associated Thrombocytopenic purpura-Thoracic surgery-Abdominal lymphadenopathy

and

organomegaly

-

Biliary

tract disease-Intracranial mass lesions-Anorectal surgery-Organ transplantation

Slide49

Surgical treatmentScreeningInformed consentOperative risk in HIV/AIDS patientsOccupational risks to the health care workersVariations in operative techniques.Universal and specific precautions.Ethics.

Slide50

Consent- HIV patients fear social recognition and rejection,and frequently request surgeons to perform un necessary surgeries such as removal of ‘tell tale’ cervical lymph nodes or parotidectomy for DILS Some patients refuse surgery in desperate situations such as bowel perforation as they want to end the suffering.

It should be emphasised to AIDS patients that they are more prone to

perioperative

complications.

Slide51

Operative risk in HIV patients The preoperative physiological status is the most accurate predictor of postoperative outcome. While calculating the risk of operative mortality and morbidity the surgeon considers two aspects -The patho physiological state of the patient versus magnitude of the procedure. For ex-

- The patients with early HIV infection have an operative risk equal to HIV

negative patients and therefore can be subjected to any major surgery.

and

- Operations in contaminated fields ex- Anorectum or oral cavity.

Slide52

Anaesthesia in HIV patientsGeneral Anaesthesia should not be withheld on the grounds of HIV infection alone.Regional anaesthesia is safeEtomidate, Atracurium,

remifentanyl

and

desflurane

are preferred

Midazolam and fentanyl are better avoided, Succinyl choline

should be used with caution

Preoperative assessment--Respiratory system-Cardiovascular system-Gastrointestinal system-Nervous system-IVDU group of diseases ( multisystem disease, poor venous access)

Reducing the risk

-Disposable equipments should be used, Laryngoscopes are exposed to

contamination mainly, if heat-moisture exchange filter is used , (PALL BB22-15MS)

it is unnecessary to change the breathing circuit.

Slide53

Operating roomSet operating room for emergency and urgency case.Limiting the personnel invoved in the caseChoosing an operating sulte remote from others.

Remove all un necessary equipments

Full PPE

Recovery of the patient should be in isolation

PPE should be disposed of leaving the OR

Fumigation.

Slide54

Variations in operative technique Simple techniques to reduce occupational hazards include-Cutting with electrocauteyAvoidance of Hand – hand passage of sharps.

Hands should never be used as tissue retractors.

Avoid blood loss.

Laporoscopic

surgeries.

Natural orifice trans-endoscopic surgery (NOTES) is on the horizon for major abdominal surgeries.

Intraoperative

taplingBanding of Haemorrhoids and varices.

Slide55

Universal and specific precautionsBarrier method-Hand hygeine Foot wear (Wellington shoes)Gloves

Water impermeable gowns

Cap and mask

Protective eye wear

Slide56

Sharps precautions-Never to recap needles.Dispose of used needles and sharps immediatedly in sharp boxes.Sharp boxes: must be easily accessible,

must not be overfilled, labelled or

color

coded

Needle incinerators can be another safe way

of disposal.Reusable sharps must be handled with care avoiding direct handling during processing.

Slide57

How to deal with used materials after surgerySoiled linen : Soaking in 1:100 hypochirite solution for 30 minutesMetal instruments: Wash with soap and water, soak in 2% Gluteraldehyde solution for 30minutes, sharp instruments for 6hrs

Then they are autoclaved.

Plastic tubing: Soaking in 2%

Gluteraldehyde

for 6 hours or ETO sterilisation.

Slide58

Ethics- If a doctor proposes an operation the risks must be weighed against potential benefits of surgery. The occupational hazard is not only to the surgeon’s life but also to the lives of his/her spouse or intimate friends but if situation demands the surgeon should take calculated risk in order to improve the well-being of the patient. Referring the patients to colleagues on ground of contamination risk is unjustified

To tell or not to tell?

Clinical categories-

Life

threatning

surgical correctable disease Surgery is must Surgical interventions for diagnosis and prophylaxis Find an alternative

Slide59

Post operative complications in HIV patients:Septic Sequelae (Pelvic collections and wound infections).Postoperative pneumonia.Renal failure.Surgical infections.

Tachycardia.

Fever.

Endometritis

and wound infection.

Slide60

Post operative careICU for monitoringVentilator support

Blood transfusion.

TPN and

nasogastric

tube is sufficient

Chest tubes

Urinary catheterization.

Slide61

Stuck or splashed?Immediate actions required-Wash needle sticks and cuts with soap and water.Flush splashes.Irrigate eyes with clean water, saline or

sterile

irrigants

for 15minutes.

Report the incident to your supervisor.

Seek medical treatment as soon as possible.

Slide62

-Prompt exposure Report regarding the time, nature etc of exposure should be reported.-Source HIV testing after proper consent, if known to be HIV positive then assess the health status and the possibility of drug resistance if on anti-retroviral therapy.-Recipient Baseline serological testing of HIV, HBV and HCV.

Slide63

Post exposure prophylaxisDecision to start PEP depends on-Severity of exposure-HIV status of sourceIf required should be started within 2-24 hours of exposure and not later than 72 hours.Effectively decreases with increasing duration since exposure.

Basic regimen:

Consists of two NRTIs for 1month

Zidovudine

300mg BD +

Lamivudine 150mg BDZidovudine 300mg BD + Stavudine 40mg BD

Didanosine

200mg BD + Stavudine 40mg BD

Slide64

Expanded regimenConsists of 2 NRTIs + 1PI for 1 monthAny of the basic regimen + any of the following:Idinavir 800mg TDSRitonavir 100mg BDSaquinavir 1000mg BD

Lopinavir

400mg BD

Slide65

HIV-AIDS- India’s ResponseNational AIDS control programme (NACP)-1987National AIDS control organization (NACO)-1992 OBJECTIVES –- Reduce new infectionsCreate awareness,Comprehensive

care, support and treatment to all persons living with HIV/AIDS.

APPROACHES-

Core high risk groups

Bridge populations, with particular focus on clients of sex workers

Other vulnerable populations.

Slide66

STRATEGIES-Promotion of STI servicesCondom useBehaviour change communicationAIDS helpline -1097‘University talk AIDS project’

Approaches- ABC (

Abstinence,befaithful,condom

), CNN –(

Condom,Needle

exchange,Negotiation).AIDS day- 1

st

December.

Slide67

FactsHIV is not airborne and cannot be caught by touching skin, sweat or salivaYou cannot get HIV by holding hands or sharing drinksMosquito’s do not inject other

peoples blood when they bite and

so cant spread HIV

Slide68

AUPASARGIKA ROGA-

Slide69

Oja Kshaya-Nidana-

Slide70

LAKSHANA

Slide71

Chikitsa

Slide72