The document summarizes key aspects of HIV and its treatment. It describes the structure of the HIV virus and the stages of early and late HIV infection. It explains how HIV attaches and replicates within cells, eventually causing AIDS through depletion of CD4 cells. Symptoms and opportunistic infections that occur are outlined. Methods of HIV transmission and testing approaches like ELISA, Western Blot, viral isolation are also summarized. Common antiretroviral drug regimens and their effects are briefly explained.
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The stages of HIV infection and viral replication
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6. • The outer shell of the virus is known as the Viral
enevlope. Embedded in the viral envelope is a complex
protein known as env which consists of an outer
protruding cap glycoprotein (gp) 120, and a stem gp14.
Within the viral envelope is an HIV protein called
p17(matrix), and within this is the viral core or capsid,
which is made of another viral protein p24(core
antigen).
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8. • In early phase HIV infection, initial
viruses are M-tropic. Their
envelope glycoprotein gp120 is
able to bind to CD4 molecules and
chemokine receptors called CCR5
found on macrophages
9. • In late phase HIV infection, most of
the viruses are T-tropic, having
gp120 capable of binding to CD4
and CXCR4 found on T4-
lymphocytes.
10. • (a) HIV (red) attaches to two cell-surface receptors (the CD4
antigen and a specific chemokine receptor).
• (b) The virus and cell membrane fuse, and the virion core
enters the cell.
• (c) The viral RNA and core proteins are released from the
virion core and are then actively transported to the nucleus.
• (d) The viral RNA genome is converted into double-stranded
DNA through an enzyme unique to viruses, reverse
transcriptase (red dot).
• (e) The double-stranded viral DNA moves into the cell
nucleus.
• (f) Using a unique viral enzyme called integrase, the viral
DNA is integrated into the cellular DNA.
• (g) Viral RNA is synthesized by the cellular enzyme RNA
polymerase II using integrated viral DNA as a template. Two
types of RNA transcripts shorter spliced RNA (h) and full-
length genomic RNA (j) are produced.
• (h) Shorter spliced RNAs are transported to the cytoplasm
and used for the production of several viral proteins that are
then modified in the Golgi apparatus of the cell (i).
• (j) Full-length genomic RNAs are transported to the cytoplasm
(k).
• (l) New virion is assembled and then buds off.
• (m) Mature virus is released.
12. • After a period of latency lasting up to 10 years viral
replication is triggered and occurs at high rate.
• CD4 cell may be destroyed in the process, body
attempts to replace lost CD4 cells, but over the
course of many years body is unable to keep the
count at a safe level.
• Destruction of large numbers of CD4 cause
symptoms of HIV to appear with increased
susceptibility to opportunistic infections, disease and
malignancy.
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14. • Methods of transmission:
– Sexual transmission, presence of STD increases
likelihood of transmission.
– Exposure to infected blood or blood products.
– Use of contaminated clotting factors by hemophiliacs.
– Sharing contaminated needles (IV drug users).
– Transplantation of infected tissues or organs.
– Mother to fetus, perinatal transmission variable,
dependent on viral load and mother’s CD 4 count.
20. Oral Hairy Leukoplakia
• Being that HIV reduces immunologic
activity, the intraoral environment is a
prime target for chronic secondary
infections and inflammatory processes,
including OHL, which is due to the
Epstein-Barr virus under
immunosuppressed conditions
21. Kaposi’s sarcoma (shown) is a rare cancer
of the blood vessels that is associated with
HIV. It manifests as bluish-red oval-shaped
patches that may eventually become
thickened. Lesions may appear singly or in
clusters
22. • CD4 count drops below 200 person is considered to have
advanced HIV disease
• If preventative medications not started the HIV infected
person is now at risk for:
– Pneumocystis carinii pneumonia (PCP)
– cryptococcal meningitis
– toxoplasmosis
• If CD4 count drops below 50:
– Mycobacterium avium
– Cytomegalovirus infections
– lymphoma
– dementia
– Most deaths occur with CD4 counts below 50.
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27. ELISA Testing
• First serological test developed to
detect HIV infection.
– Easy to perform.
– Easily adapted to batch testing.
– Highly sensitive and specific.
• Antibodies detected in ELISA include
those directed against: p24, gp120,
gp160 and gp41, detected first in
infection and appear in most
individuals
28. ELISA Testing
• ELISA tests useful for:
– Screening blood products.
– Diagnosing and monitoring
patients.
– Determining prevalence of
infection.
– Research investigations
30. Western Blot
• Antibodies to p24 and p55
appear earliest but decrease
or become undetectable.
• Antibodies to gp31, gp41, gp
120, and gp160 appear later
but are present throughout all
stages of the disease.
32. • Can be used to detect both virus and
antibody to it.
• Antibody detected by testing patient
serum against antigen applied to a slide,
incubated, washed and a fluorescent
antibody added.
• Virus is detected by fixing patient cells
to slide, incubating with antibody.
33. • Virus isolation can be used to definitively
diagnose HIV.
• Best sample is peripheral blood, but can use
CSF, saliva, cervical secretions, semen, tears
or material from organ biopsy.
• Cell growth in culture is stimulated, amplifies
number of cells releasing virus.
• Cultures incubated one month, infection
confirmed by detecting reverse transcriptase
or p24 antigen in supernatant.
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36. We can reduce sexual transmission of HIV.
•We can prevent mothers from dying and babies from becoming
infected with HIV.
•We can ensure that people living with HIV receive treatment.
•We can prevent people living with HIV from dying of tuberculosis.
•We can protect drug users from becoming infected with HIV.
37. Sustiva + Truvada Treatment
• Sustiva + Truvada (FTC + tenofovor) is one of the most
popular and effective starting HIV regimens.
• Many patients will have dream/sleep/central nervous
system effects particularly in the first month (due to the
Sustiva).
• Upset stomach/bloating/gas/loose stools is also fairly
common during the first month and for most patients is
fairly mild.
• HIV levels in the blood will often drop by > 99% in the
first month and the CD4 count (marker of immune
system function) will often increase providing protection
against AIDS related diseases within weeks/months of
starting the medication.
38. Truvada
• Truvada is made up of HIV drugs from a
class called nucleoside/nucleotide reverse
transcriptase inhibitors (NRTIs), also
known as “nukes.”
• The NRTIs block reverse transcriptase, a
protein that HIV needs to make more
copies of itself. This may slow down HIV
disease