Microbiology, Chapter 20, HIV

1
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.

2
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.
3
Fig. 20.22
4
Fig. 20.24
5
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 1950s and 1960s. 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)

6
Origin of aids controversial, similar to SIV
7
(No Transcript)
8
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.

9
Fig. 20.24
10
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

11
HIV

• 6. Damage to the host
• 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.

12
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
13
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.

14
Tests for HIV
15
(No Transcript)
16
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.
17
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.

18
Fig. 20.21
19
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.
20
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.
21
Fig. 20.21
22
(No Transcript)
23
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

24
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 Kaposis
  sarcoma, lymphoma, and
• Scervical cancer

25
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

26
Fig. 20.23
27
Fig. 20.25
28
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??
  

29
(No Transcript)
30
Fig. 20.24