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Pamantasan ng Lungsod ng Maynila

College of Medicine
Department of Biochemistry and Nutrition

HUMAN
IMMUNODEFICIENCY
VIRUS / AIDS
BONDAD, BRAVO, CANDELARIA, CAPILI, CONCEPCION

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Learning Objectives
01 To differentiate HIV
from AIDS

To describe the virus


02
that causes HIV and
AIDS

To describe the clinical


03 presentation of HIV
and AIDS
Learning Objectives
To discuss the
04 pathophysiology of HIV
/ AIDS

To discuss the
05 management and
prevention of HIV /
AIDS

To explain the
06 mechanism of action of
drugs used in HIV and
AIDS
1. To differentiate HIV from
AIDS
Human Immunodeficiency
Virus
● Is a virus that damages the cells in
your immune system and weakens
your ability to fight everyday infections
and disease.

● Genus: Lentivirus
● Family: Retroviridae
● Subfamily: Orthoretrovirinae
Human Immunodeficiency
Virus
● HIV was introduced during 1920-1940
● HIV 1 - from non-human primate immunodeficiency viruses
from Central African chimpanzees
● HIV 2 - from West African sooty mangabeys
Acquired immune deficiency
syndrome

● Occurs when the HIv virus has severely damaged the


immune system
● Severe reduction in CD4+ T cells making them
vulnerable to contracting life-threatening infections
HIV vs AIDS

● Major difference is that AIDS cannot be transmitted


● Early diagnosis and effective treatment can prevent them
from having AIDS
2. To describe the virus that
causes HIV and AIDS
Virus
- a small parasite that cannot reproduce
by itself.
- Once it infects a susceptible cell > a
virus can direct the cell machinery to
produce more viruses.
- RNA or DNA as their genetic material
> may be single- or double-stranded.
- Simplest viruses: enough RNA or DNA
to encode four proteins
- Most complex: 100 – 200 proteins.
Human Immunodeficiency Virus
(HIV)
HIV: taxonomy
Family: Retroviridae
Subfamily: Orthoretrovirinae
Genus: Lentivirus
Species: HIV-1, HIV-2
HIV: Morphology
- Each virion expresses 72 glycoprotein
projections composed of gp120
(orange) and gp41 (light blue).
- Gp41 is a transmembrane molecule
that crosses the lipid bilayer of the
envelope.
- Gp120 is noncovalently associated
with gp41 and serves as the viral
receptor for CD4 on host cells.
- The viral envelope also contains some
host-cell membrane proteins such as
class I and class II MHC molecules.
HIV: Morphology
- Within the envelope is the viral core,
or nucleocapsid, which includes a
layer of a protein called p17 (green)
and an inner layer protein called p24
(yellow).
- The HIV genome consists of two
copies of ssRNA, which are associated
with two molecules of reverse
transcriptase p64 (light red) and
nucleoid proteins p10, a protease
(red), and p32, an integrase (dark
blue).
HIV: Origin and History
HIV: Origin and History
HIV: Origin and History
HIV: Origin and History
HIV: epidemiology
HIV: epidemiology
HIV: epidemiology

January 1984-January 2018: 51,409 HIV CASES


HIV: epidemiology
In January 2018,
there were 1,021 new
HIV antibody
seropositive
individuals reported.
HIV: epidemiology
GENOTYPE SHIFT to HIV EPIDEMIC
Subtype B → Subtype AE
Subtype C - most common subtype in
the world; 50% of all cases - Africa
Subtype B - most studied; more
common in the US and Europe
Subtype AE - more aggressive and
more transmissible; Thailand
3. To describe the clinical
presentation of HIV and AIDS
HIV: symptoms
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4. To discuss the
pathophysiology of HIV / AIDS
HIV Life cycle
Attachment

Fusion

Reverse Transcription

Integration

Replication

Assembly

Budding
HIV Life cycle
Attachment

● Glycoprotein gp120
binds to co-receptor,
CCR5 and CXCR4 of a
CD4+ cell

Fusion

● Virus fuses with cell


membrane and
releases its viral core
into the cytoplasm
HIV Life cycle
Reverse Transcription

● Viral core dissociates,


leaving viral RNA and
undergoes reverse
transcription via the enzyme,
reverse transcriptase

Integration

● Viral RNA is then


combined with host
chromosomal DNA
HIV Life cycle
Replication

● Host cell produces


proteins both of host
and virus, creating
more HIV viruses

Assembly and Budding

● Viruses gather in the cell


membrane, are activated,
and then released into
the system to infect other
CD4+ cells
5. To discuss the management
and prevention of HIV / AIDS
MANAGEMENT AND PREVENTION OF HIV/AIDS

1. ART/Antiretroviral Therapy
● The administration of different drugs to manage patients with
HIV/AIDS
● Highly recommended if the patient exhibits one or more of the
following:
• You have severe symptoms.
• You have an opportunistic infection.
• Your CD4 T cell count is under 350.
• You're pregnant.
• You have HIV-related kidney disease.
• You're being treated for hepatitis B or C.
MANAGEMENT AND PREVENTION OF HIV/AIDS
ART Drug Classes:
1. Nucleoside reverse
transcriptase inhibitors
(NRTIs)
2. Non-nucleoside reverse
transcriptase inhibitors
(NNRTIs)
3. Protease inhibitors (PIs)
4. Fusion inhibitors
5. CCR5 antagonists
6. Integrase strand transfer
Figure X. Seven drug classes of Antiretroviral Therapy for
inhibitors (INSTIs) HIV/AIDS patients
7. Post attachment inhibitors
MANAGEMENT AND PREVENTION OF HIV/AIDS

2. PrEP and PEP


● Pre-exposure prophylaxis (PrEP) is medication taken daily by
people who are at high risk of getting HIV.
● Truvada® (tenofovir and emtricitabine)
● Lowers the risk of getting infected by 44% to 92%

● Post-exposure Prophylaxis (PEP) means taking ART after being


potentially exposed to HIV to prevent becoming infected
● Taken during emergency situations and must be started within 72
hours after a recent possible exposure to HIV.
MANAGEMENT AND PREVENTION OF HIV/AIDS

Figure X. PrEP poster


MANAGEMENT AND PREVENTION OF HIV/AIDS

3. Safe Child Conception and Pregnancy


● Serodiscordant couples
● Through ART:
○ Lesser chances for the HIV-positive partner to
transmit the disease to his HIV-negative partner
○ Promotion of pMTCT (Prevention of Mother-To-Child
Transmission) -- 2% chance of transmission only
MANAGEMENT AND PREVENTION OF HIV/AIDS

4. Suppression of CCR5 Cell Surface Receptor

● “Berlin patient”
● Blocking CCR5 through gene therapy
● A zinc-finger nuclease has been used in a Phase I trial of
12 humans and led to an increase in CD4 count and
decrease in their viral load while off antiretroviral
treatment
MANAGEMENT AND PREVENTION OF HIV/AIDS

5. Constant Screening and Monitoring


● According to the Infectious Diseases Society of America’s (IDSA)
guidelines:
○ Screening for diabetes, osteoporosis, and colon cancer
○ Lipid monitoring and management of lipids against
cardiovascular disease risk
○ Blood monitoring for viral levels every 6-12 months for
patients with well-controlled infection
○ Annual trichomoniasis screening for all women
○ Annual gonorrhea and chlamydia screening for men and
women
MANAGEMENT AND PREVENTION OF HIV/AIDS

6. Lifestyle Change
● Change in diet
● Vaccinations
● Avoidance of parasite hosts
● Safe sex practices
MANAGEMENT AND PREVENTION OF HIV/AIDS

7. Potential HIV Vaccine

● HVTN 702
● 31.2% effective at preventing HIV infection over the
3.5-year follow-up after vaccination
● Mixture of Canarypox vector-based vaccine called
ALVAC-HIV and a two-component gp120 protein subunit
vaccine
6. To explain the mechanism of
action of drugs used in HIV and
AIDS
Nucleoside Analogs
(NRTIs)

Competes with normal cellular


nucleosides by acting as an
alternative substrate. Terminates
the growing of DNA chain of virus.
Non-nucleoside reverse
transcriptase inhibitors(NNRTIs)

Binds to RT enzyme. Polymerase


activity is reduced and changes in
the spatial conformation occurs.
Non-competitive inhibitor.
Protease Inhibitors

Targets the protease enzyme of HIV1


which catalyzes the processing of
gag-pol polyprotein precursor and virion
gag. This is essential for viral
maturation.
Entry Inhibitors

Targets the protease enzyme of HIV1


which catalyzes the processing of
gag-pol polyprotein precursor and virion
gag. This is essential for viral
maturation.
Integrase Inhibitors

Distorts the enzyme interaction


with divalent cations and correct
positioning of viral DNA by binding
near to the active site of enzyme
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