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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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HIVHIV -- The VirusThe Virus
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HIVHIV -- The VirusThe Virus
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HIVHIV -- The VirusThe Virus
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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Occupational TransmissionOccupational Transmission
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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Occupational TransmissionOccupational Transmission
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 and AIDSHIV and AIDS
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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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HIV and AIDSHIV and AIDS
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Good correlation betwee
number of HIV particles
measured by PCR and
progression to disease
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HIV and AIDSHIV and AIDS
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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!