HIV and Related Infections

Part I
Hassan Mohammad AlShehri
Intoduction

Acquired Immunodeficiency syndrome

first described in 1981

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

AIDS first described at KSA in1985.

HIV – The Virus
HIV - The Virus
 Family of human retroviruses (Retroviridae)
Subfamily of lentiviridae

 RNA viruses whose hallmark is the reverse transcription of its

genomic RNA to DNA by the enzyme reverse transcriptase

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

 • 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)
HIV - The Virus
HIV - The Virus
HIV - The Virus
 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.

 The bonding between gp120 and gp41 is only loose and therefore
gp120 may be shed spontaneously within the local environment.

 The viral particle contains all the enzymatic equipment that is

necessary for replication: a reverse transcriptase (RT), an integrase
p32 and a protease p11
 HIV-1 Genotypes
 There are 3 HIV-1 genotypes; M (Major), O (Outlayer), N ( non M non
O), P (Pending the identification of further human cases)
 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
 O and N group subtypes not clearly defined, especially since there are
so few N group isolates. Mainly seen in Africa like HIV-2
 P a newly analyzed HIV sequence in 2009. Single case of Cameroonian
woman residing in France.
 As yet, different HIV-1 genotypes are not associated with different
courses of disease nor response to antiviral therapy.
How do you get HIV-AIDS?
 Transmission Routes
 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 organ
transplants 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).
Transmission Routes
 Sexual Intercourse
The higher the viral load, the more infectious
the patient.
The lower the viral load, the less infectious the
patient.
 A prospective study of 415 HIV-discordant
couples in Uganda showed that of 90 new
infections occurring over a period of up to 30
months, none was from an infected partner
with a viral load below 1,500 copies/ml.
 Intravenous Drug Use
 IV drug abusers represent the second largest AIDS patient groups in
the US and Europe.
 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.
 Haemophiliacs were one of the first risk groups to be identified.
Mother-to-Child
 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.

 In developed countries, vertical HIV infection has become rare

since the introduction of antiretroviral transmission prophylaxis and
elective cesarean section.
Occupational Transmission
 Occupational Transmission
A 1995 study estimated that although 600,000 to
800,000 needlestick injuries occurred among
healthcare workers every year in the USA,
occupational infection was not frequent. The risk
of occupational HIV transmission from
contaminated needles to healthcare workers was
found to be 0.3 % in case series performed prior
to the availability of potent ART.
Occupational Transmission
Risk of transmission from an infected
health care worker to patients is extremely
low; in fact, too low to be measured
accurately.
Transmission by other body fluids
Although 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, or
urine.

Transmission of HIV by a human bite can

occur but is rare.
 You can't get HIV by:

Being in the same room with someone who

has HIV.
Sharing a knife or fork, sheets, toilet seats,
or phones with someone who has HIV
Kissing a person with HIV
Shaking hands with someone with HIV
Getting bitten by a mosquito or other bug
HIV Replication
HIV - The Virus
Replication
The first step of infection is the binding of
gp120 to the CD4 receptor of the cell,
which is followed by penetration and
uncoating.
The RNA genome is then reverse
transcribed into a DNA provirus which is
integrated into the cell genome.
This is followed by the synthesis and
maturation of virus progeny.
Natural history of the disease
 HIV and AIDS
The cellular and immunological picture - The course of the disease

virus

antibody
CD4 cells

25
HIV and AIDS
 HIV Pathogenesis
 The profound immunosuppression seen in AIDS is due to the
depletion of T4 helper lymphocytes.
 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).
 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.
 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).
 Acute Viral Syndrome
 The natural history described in the following refers to HIV infection
in the absence of HAART.

 Defined as the time period from initial infection with HIV to the
development of an antibody response.
 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.
 There is usually a high plasma viremia and frequently a marked
decrease in CD4+ T-cells. The CD4+ T-cell count later increases
again, normally to levels inferior to the pre-infection values
 Latency Period
 Term .latency period. may be misleading, given the incredibly high
turnover of the virus and the relentless daily destruction of CD4+ T-
cells.
 At the end of the latency period, a number of symptoms or illnesses
may appear which do not fulfil the definition of AIDS
 Include slight immunological, dermatological, hematological and
neurological signs. Many of them are listed in the Category B of the
CDC classification system.
 Constitutional symptoms, such as fever, weight loss, night sweats, and
diarrhea may also develop. In this situation, the level of 200 CD4+ T-
cells/µl is an important cut-off, below which the risk of many AIDS-
defining illnesses increases
 latency may last 8-10 years or more.
HIV and AIDS

Good correlation between

number of HIV particles
measured by PCR and
progression to disease

33
HIV and AIDS

CD4 cell count is not a

good predictor of
progression to disease

34
Diagnosis
 Laboratory Diagnosis
 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.
 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.
 Confirmatory assays - Western blot is regarded as the gold standard for
serological diagnosis. However, its sensitivity is lower than screening
EIAs.
ELISA
 False-positive results can occur with:
 Antibodies to class II antigens
 Autoantibodies
 Hepatic disease
 Recent influenza vaccination
 Acute viral infections

ELISA
Western Blot
Most commonly used confirmatory test
Detects antibodies to HIV antigens of
specific molecular weights
Antibodies to HIV begin to appear within 2
weeks of infection.
Period of time between initial infection and
development of detectable antibodies is
rarely >3 months.
Western blot for HIV antibody

The most important antibodies

are those against the
envelope glycoproteins gp120,
gp160, and gp41
Western blot for HIV antibody
Algorithm of serologic testing
Direct Detection of HIV

 These tests are useful in:

◦ Patients with a positive or indeterminate EIA result and an

indeterminate Western blot result or
◦ Patients in whom serologic testing may be unreliable (such as
those with hypogammaglobulinemia)
Direct detection of HIV
Tests:
 Immune complex dissociated p24 antigen capture assay
 Plasma p24 antigen levels increase during the first few weeks following infection,
before the appearance of anti-HIV antibodies.

 HIV RNA by polymerase chain reaction (PCR)

 HIV RNA by branched DNA
 HIV RNA by nucleic acid sequence-based assay

PCR
 Rapid Tests
Rapid tests are similar to the standard
ELISA test in that they look for antibodies to
HIV in the patient’s blood+/-saliva+/-serum.
They are called “rapid” because the results
are available within an hour or less.
Reading Results: Genie II

Non-reactive Reactive
 Reading Results: Determine

Non- Reactive

Reactive

Reactive

Sample Control line

Test line
Pad
Lab workers Health workers Counselors
Reading Results: OraQuick

Reactive

Non-
Reactive
References
 http://www.cdc.gov/hiv/resources/reports/hiv_prev_us.htm
 http://www.cdc.gov/nchhstp/newsroom/docs/FastFacts-MSM-
FINAL508COMP.pdf
 http://www.co.sanmateo.ca.us/vgn/images/portal/cit_609/31/5/1021425659
factors_delayed_hiv_article.pdf
 Kumar and Clark Clinical Medicine
 Harrison principle of internal medicine
 Harrison's Principle of Internal Medicine
 plaza.ufl.edu/mounaht/Group%25209%2520Chapter
%252030%2520Lesson%25202%2520Powerpoint(new)
%255B1%255D.ppt
THANK
YOU!