HIV Presentation 1

8/9/2019 HIV Presentation 1

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HIV and Related InfectionsHIV and Related Infections

Part IPart I

HassanHassan MohammadMohammad AlShehriAlShehri


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IntoductionIntoduction

y Acquired Immunodeficiency syndrome firstdescribed in 1981

y HIV-1 isolated in 1983, and HIV-2 in 1986

y

AIDS first described at KSA in1985.


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HIVHIV The VirusThe Virus


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HIVHIV -- The VirusThe Virus

y Family of human retroviruses (Retroviridae)

Subfamily of lentiviridae

y RNA viruses whose hallmark is the reverse transcription ofits genomic RNA to DNA by the enzyme reverse transcriptase

y HIV-1 is the most common cause of AIDS worldwide.

y HIV-2 has been identified predominantly in western Africa.

Small numbers of cases have also been reported in

Europe, South America, Canada, and the U.S.

Has ~40% sequence homology with HIV-1

More closely related to simian immunodeficiency viruses

(monkeys)


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y Each viral particle contains 72 glycoprotein complexes, which

are integrated into this lipid membrane, and are each

composed of an external glycoprotein gp120 and a

transmembrane spanning protein gp41.

y The bonding between gp120 and gp41 is only loose and

therefore gp120 may be shed spontaneously within the local

environment.

y

The viral particle contains all the enzymatic equipment that isnecessary for replication: a reverse transcriptase (RT), an

integrase p32 and a protease p11


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HIVHIV--1 Genotypes1 Genotypes

y There are 3 HIV-1 genotypes; M (Major), O (Outlayer), N ( non M

non O), P (Pending the identification of furtherhuman cases)

y M group comprises of a large number subtypes and recombinant forms

Subtypes - (A, A2, B, C, D, F1, F2, G, H, J and K)

Recombinant forms - AE, AG, AB, DF, BC, CD

y O and N group subtypes not clearly defined, especially since there are

so few N group isolates. Mainly seen in Africa like HIV-2

y P a newly analyzed HIV sequence in 2009. Single case ofCameroonian woman residing in France.

y As yet, different HIV-1 genotypes are not associated with different

courses of disease nor response to antiviral therapy.


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How do you get HIVHow do you get HIV--AIDS?AIDS?


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Transmission RoutesTransmission Routes

y HIV infection can be transmitted through:

unprotected sexual intercourse with an infected partner.

injection or transfusion of contaminated blood or blood products

(infection through artificial insemination, skin grafts and organtransplants is also possible);

sharing unsterilized injection equipment that has been previously

used by someone who is infected;

maternofetal transmission (during pregnancy, at birth, and

through breastfeeding).


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Transmission RoutesTransmission Routes


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Sexual IntercourseSexual Intercourse

y The higher the viral load, the moreinfectious the patient.

y The lower the viral load, the less infectious

the patient.y A prospective study of 415 HIV-discordant

couples in Uganda showed that of 90 newinfections occurring over a period of up to

30 months, none was from an infectedpartner with a viral load below 1,500copies/ml.


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Intravenous Drug UseIntravenous Drug Use

y IV drug abusers represent the second largest AIDS patient

groups in the US and Europe.

y In contrast to the accidental needle stick injury, the risk of

transmission through sharing injection equipment is far higher:

the intravenous drug user ensures the proper positioning of the

needle by aspiration of blood.

y Haemophiliacs were one of the first risk groups to be identified.


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MotherMother--toto--ChildChild

y In the absence of any intervention, an estimated 15-30 % of

mothers with HIV infection will transmit the infection during

pregnancy and delivery. In approximately 75 % of these

cases, HIV is transmitted during late pregnancy or during

delivery.10-15 % are caused by breastfeeding.

y In developed countries, vertical HIV infection has become

rare since the introduction of antiretroviral transmission

prophylaxis and elective cesarean section.


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Occupational TransmissionOccupational Transmission


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yA 1995 study estimated that although

600,000 to 800,000 needlestick injuries

occurred among healthcare workers everyyear in the USA, occupational infection was

not frequent. The risk of occupational HIV

transmission from contaminated needles to

healthcare workers was found to be0.3

% incase series performed prior to the availability

of potent ART.


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y Risk of transmission from an infected

health care worker to patients is

extremely low; in fact, too low to bemeasured accurately.


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Transmission by other body fluidsTransmission by other body fluids

yAlthough the virus can be identified from

virtually any body fluid, there is no

evidence that HIV can be transmitted as

a result of exposure to saliva, tears,

sweat, orurine.

y Transmission of HIV by a human bitecan occur but is rare.


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You can't get HIV by:You can't get HIV by:

y Being in the same room with someone

who has HIV.

y

Sharing a knife or fork, sheets, toiletseats, or phones with someone who

has HIV

y Kissing a person with HIV

y Shaking hands with someone with HIV

y Getting bitten by a mosquito or other

bug


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HIV ReplicationHIV Replication


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HIVHIV -- The VirusThe VirusHIVHIV -- The VirusThe Virus


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ReplicationReplication

y The first step of infection is the binding ofgp120 to the CD4 receptor of the cell,which is followed by penetration and

uncoating.y The RNA genome is then reverse

transcribed into a DNA provirus which isintegrated into the cell genome.

y This is followed by the synthesis andmaturation of virus progeny.


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Natural history of the diseaseNatural history of the disease


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HIV and AIDSHIV and AIDS

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The cellular and immunological picture - The course of the disease

virus

CD4 cellsantibody


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HIV PathogenesisHIV Pathogenesis

y The profound immunosuppression seen in AIDS is due to the depletion

ofT4 helper lymphocytes.

y In the immediate period following exposure, HIV is present at a high

level in the blood (as detected by HIV Antigen and HIV-RNA assays).

y It then settles down to a certain low level (set-point) during the

incubation period. During the incubation period, there is a massive

turnover of CD4 cells, whereby CD4 cells killed by HIV are replaced

efficiently.

y Eventually, the immune system succumbs and AIDS develop when

killed CD4 cells can no longer be replaced (witnessed by high HIV-

RNA, HIV-antigen, and low CD4 counts).


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Acute Viral SyndromeAcute Viral Syndrome

y The naturalhistory described in the following refers to HIV

infection in the absence of HAART.

y Defined as the time period from initial infection with HIV to the

development of an antibody response.y Shows symptoms that often resemble those of mononucleosis.

These appear within usually 2 - 12 weeks following exposure to

HIV. However, clinical signs and symptoms may not occur in all

patients.

y

There is usually a high plasma viremia and frequently a markeddecrease in CD4+ T-cells. The CD4+ T-cell count later

increases again, normally to levels inferior to the pre-infection

values


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Latency PeriodLatency Period

y Term .latency period. may be misleading, given the incredibly

high turnover of the virus and the relentless daily destruction of

CD4+ T-cells.

y At the end of the latency period, a number of symptoms or

illnesses may appear which do not fulfil the definition of AIDS

y Include slight immunological, dermatological, hematological and

neurological signs. Many of them are listed in the Category B of

the CDC classification system.

y Constitutional symptoms, such as fever, weight loss, night

sweats, and diarrhea may also develop. In this situation, the

level of 200 CD4+ T-cells/l is an important cut-off, below which

the risk of many AIDS-defining illnesses increases

y latency may last 8-10 years or more.


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Good correlation betwee

number of HIV particles

measured by PCR and

progression to disease


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CD4 cell count is not

a

good predictor of

progression todisease


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DiagnosisDiagnosis


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Laboratory DiagnosisLaboratory Diagnosis

y Serology is the usual method for diagnosing HIV infection. Serological

tests can be divided into screening and confirmatory assays. Screening

assays should be as sensitive whereas confirmatory assays should be as

specific as possible.y Screening assays - ELISA is the most frequently used screening assays.

The sensitivity and specificity of the presently available commercial

systems now approaches 100% but false positive and negative reactions

occur. Some assays have problems in detecting HIV-1 subtype O.

y Confirmatory assays - Western blot is regarded as the gold standard for

serological diagnosis. However, its sensitivity is lower than screening

EIAs.


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ELISAELISA

y False-positive results can occur with:

x Antibodies to class II antigens

x Autoantibodies

x Hepatic disease

xRecent influenza vaccination

x Acute viral infections

ELISA


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Western BlotWestern Blot

y Most commonly used confirmatory test

y Detects antibodies to HIV antigens of

specific molecular weights

yAntibodies to HIV begin to appear within

2 weeks of infection.

y Period of time between initial infection

and development of detectableantibodies is rarely >3 months.


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Western blot for HIV antibodyWestern blot for HIV antibody

The most important antibodies

are those against theenvelope glycoproteins gp120,

gp160, and gp41


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Western blot for HIV antibodyWestern blot for HIV antibody


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Algorithm of serologic testingAlgorithm of serologic testing


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Direct Detection of HIVDirect Detection of HIV

y These tests are useful in:

Patients with a positive or indeterminate EIA result and an

indeterminateWestern blot result or Patients in whom serologic testing may be unreliable (such

as those with hypogammaglobulinemia)


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Direct detection of HIVDirect detection of HIV

y Tests:y Immune complex dissociated p24 antigen capture assay

x Plasma p24 antigen levels increase during the first few weeks following

infection, before the appearance of anti-HIV antibodies.

y HIV RNA by polymerase chain reaction (PCR)

y HIV RNA by branched DNA

y HIV RNA by nucleic acid sequence-based assay

PCRPCR


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Rapid TestsRapid Tests

y Rapid tests are similar to the standard

ELISA test in that they look for

antibodies to HIV in the patients

blood+/-saliva+/-serum.y They are called rapid because the

results are available within an hour or

less.


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Non-reactive Reactive

Reading Results: Genie IIReading Results: Genie II


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Non- Reactive

Reactive

Sample

Pad

Reading Results: DetermineReading Results: Determine

Control lineTest line

Lab workers Health workers Counselors

Reactive


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Reading Results:Reading Results: OraQuickOraQuick

Reactive

Non-Reactive


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ReferencesReferences

y http://www.cdc.gov/hiv/resources/reports/hiv_prev_us.htm

y http://www.cdc.gov/nchhstp/newsroom/docs/FastFacts-MSM-

FINAL508COMP.pdf

y http://www.co.sanmateo.ca.us/vgn/images/portal/cit_609/31/5/10214

25659factors_delayed_hiv_article.pdf

y Kumar and Clark Clinical Medicine

y Harrison principle of internal medicine

y Harrison's Principle of Internal Medicine

y plaza.ufl.edu/mounaht/Group%25209%2520Chapter%252030%252

0Lesson%25202%2520Powerpoint(new)%255B1%255D.ppt


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THANKTHANK

YOU!YOU!

HIV Presentation 1

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