Microbiology, Chapter 20, HIV
Pull up HIV separate handout from Unit 4
notes. You are responsible for that material.
The following slides from your text help
explain some of those concepts.
Aids: Acquired Immune Deficiency Syndrome (Rev. 10/06)
1. Caused by the HIV virus (human immunodeficiency virus – a retro virus)
2. Rna virus, with reverse transcriptase for a copy of viral DNA, which is
then transcribed into viral RNA.
3. Some retroviruses can become incorporated into host DNA genome.
This may occur with HIV – an example of viral latency. A second
enzyme, integrase, helps to splice the viral DNA into host DNA
genome. Another enzyme, a protease, helps cut the new viral
proteins coded for by the viral nucleic acid, into viral capsid
subuinits.
These bud from the cells, acquiring their envelope as virus leaves
host cells. See pg 640.
Fig. 20.22
Fig.
20.24
HIV
• 4. Origin HIV: most researchers feel the virus
originated in west Africa, somewhere
• between 40 and 100 years ago. This infection
was contained in a small area, probably
• remote, until the 1950’s and 1960’s. Both social
and political upheaval in Africa as well
• as the development of rapid and wide spread
travel contributed to its spread. (this is
• theoretical – an emerging disease – contained
for long time and then spread)
Origin of aids; controversial, similar
to SIV
HIV transmission
• 5. Transmission of HIV
– a. HIV is extremely labile in a free state and cannot
readily enter through intact body
– surfaces.
– b. HIV has been detected in a number of body fluids
including blood, semen, cervical secretions, breast
milk, urine, CSF, saliva, and tears. According to most
sources, the last four are not likely a mode of
transmission.
– c. The most common routes of transmission in the US
are sexual contact, IV drug use, and vertical passage
from infected mothers to offspring.
– d. Since 1985, transmission by blood transfusion has
been rare due to good testing of blood supply and
heat treatment of plasma products.
Fig.
20.24
HIV
•
•
•
e. Although in the US, the HIV infection and resulting aids cases have been
predominately spread through the gay community, the percentage of
heterosexual transmission has been increasing. This is due, according to
epidemiologists, to the spread of HIV through use of contaminated needles
by IV drug users. There is also and increase in the spread of HIV from
infected mothers to fetuses.
f. There is ample evidence that the spread of HIV infection in less
developed countries is overwhelmingly heterosexual.
CDC.gov 2005
HIV
6. Damage to the host:
a. HIV specifically damages T helper lymphocytes, called T4 because they have
an antigen CD4 on the surface of the cell. The CD4 receptors, plus a
co-receptor, are the site of attachment for HIV. The viral envelope fuses with the
cell membrane and releases the viral enzymes and two strands of RNA of the
HIV genome. Pg639
b. Many cells are killed as the virus replicates. The acute stage of the infection,
lasting some where around 6 weeks or so, is marked by rapid viral replication
and killing CD4 cells. Many people will have symptoms similar to other viral
infections, such as fever, enlarged lymph nodes, rash, muscles aches, and
headaches.
c. The immune response to such and infection holds the viral replication in check,
but does not eliminate the virus. A steady state of viral replication is then
reached, which is the chronic phase. CD4 cell levels remain high enough to hold
secondary infections in check.
HIV
d. Eventually, the continued assault on the T4 cells leads
to an imbalance in the ratio of (helper / suppressor /
cytotoxic) lymphocytes. This leads to an even
further suppression of the immune response. The
course of the disease can vary tremendously
from one individual to another.
e. Since the T helper cells also help regulate the B cells,
as well as macrophages, these immune functions
are also damaged. Graph pg. 637
HIV
• 7. Diagnosis
• a. Symptoms, or clinical findings – will be
discussed more in aids
section
– b. Serology:
• i. EIA tests for antibodies against the HIV virus
– 1. Enzyme linked immuno assay. The body may produce
antibodies
» in 6 to 12 weeks, it is currently recommended that a person
be tested 3 months after engaging in risky behavior, to
allow the body time to produce detectable antibody levels
(titer). If this test is negative a follow up test is
recommended in 3 months.
– 2. The first positive EIA test is followed by a second test, and
then confirmed by another test called the western blot test.
» This is a method to measure antibodies against individual
viral polypeptides.
Tests for HIV
HIV
3. There is some difficulty in false positives – especially in
comparing low risk and high risk groups. So several tests are
done to make sure there are no false positives or missed
positives.
4. It is also important to clarify that a positive HIV antibody
test signifies current infection. It is extremely important,
therefore that such individuals be counseled on the issues
involved in HIV transmission so that further spread can be
minimized.
HIV
• c. One measure of this progression is the number of cd4
lymphocytes present in the blood. Since these are
the main target cells for infection, a low number
would indicate that the infection is becoming more
serious. Measures of viral load (the number of viral
RNA per milliliter of blood plasma) can help monitor
the infections progress and have aided in the
understanding of both the disease process and the
means of therapies to hold viral replication in check.
• d. The designation of aids related complex, ARC, has
been used in the past to type the beginning of the
aids disease. This is an artificial separation that is
not being used much today.
Fig. 20.21
HIV
8. Aids: Aids is a constellation of clinical illnesses, primarily opportunistic
infections, and malignancies that are the consequences of the
destruction of the immune system by the HIV virus.
a. HIV infections and aids are not synonyms. HIV infection can initially
resemble many viral infections, with symptoms such as a low
grade fever, swollen lymph nodes, and a rash. This is followed by
a period of time referred to as “clinical latency”, where symptoms
do not occur for a period of months to years.
b. At the present time, a person who has been diagnosed with a positive
HIV test will eventually develop aids. There is still quite a bit to
learn about the progression of the disease. There is a lot variability
among individual HIV and aids patients.
HIV
c. One measure of this progression is the number of cd4
lymphocytes present in the blood. Since these are
the main target cells for infection, a low number
would indicate that the infection is becoming more
serious. Measures of viral load (the number of viral
RNA per milliliter of blood plasma) can help monitor
the infections progress and have aided in the
understanding of both the disease process and the
means of therapies to hold viral replication in check.
d. The designation of aids related complex, ARC, has been
used in the past to type the beginning of the aids
disease. This is an artificial separation that is not
being used much today.
Fig. 20.21
HIV
e. Early signs, in addition to viral load and the lower
T4 cell levels are:
i. Weight loss
ii. Fever that persists for longer than a
month
iii. Persisting diarrhea
iv. Recurrent oral or vaginal Candidiasis
in females
v. Herpes zoster
vi. Fatigue
HIV
f. Later symptoms fall into two categories:
i. Infectious diseases:
1. Opportunistic infections such as
Cryptosporidium, Toxoplasmosis,
Pneumocystis, Candida, Cryptococcus
2. Mycobacterial infections such as Tb or M.
avium
3. Viral infections such as CMV, or Herpes
simplex
ii. Oncological manifestations such as Kaposi’s
sarcoma, lymphoma, and
Scervical cancer
HIV
9. Treatment: pg 644
A. All approved anti-HIV drugs attempt to block viral
replication within cells by inhibiting either reverse
transcriptase or the hiv proteases.
1. Reverse transcriptase inhibitors:
nucleoside analogues (“look alikes” for HIV DNA azt, idanosine, lamivudine, stavudine, and
zalcitabine
2. Non-nucleoside analogues targeting reverse
transcriptase:
delavirdine and nevirapine
3. Protease inhibitors: indinavir, nelfinavir, ritonavir
Fig.
20.23
Fig. 20.25
HIV
B. Recommended therapy: current recommended therapy is
called HARRT: highly active antiretroviral therapy.
This consists of triple therapy, including two
nucleoside analogues and a protease inhibitor. This
means between 8 and 16 or even more pills a day at
a cost of 10,000 – 12,000 dollars per year.
C. Prevention:
1. No vaccine
2. Education is the best and most effective tool. The
target would be general but a significant strategy is
need for high risk populations – homosexual
community and IV drug abusers??
Well planned,
continuing, good follow up studies??
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Fig.
20.24