Human immunodeficiency virus

R.NAGALAKSHMI
ASSISTANT PROFESSOR
THE OXFORD COLLEGE OF PHARMACY
BANGALORE
 Human immunodeficiency virus
HIV is a lentivirus (a subgroup of retrovirus) that causes HIV infection and over
time acquired immunodeficiency syndrome (AIDS)
Human Immunodeficiency Virus (HIV)- virus that primarily infects cells of the
immune system and that causes AIDS
Acquired Immune Deficiency Syndrome (AIDS)- disease that is caused by HIV
infection, which weakens the immune system
Pandemic- disease that spreads quickly through human populations all over the
world
HIV invades the helper T cells to replicate itself. No Cure
Acquired Immunodeficiency Syndrome
HIV is the virus that causes AIDS. Disease limits the body’s ability to fight infection
A person with AIDS has a very weak immune system
• Helper T Cell- white blood cell that activates the immune response and that is the
primary target cell of HIV infection
• Opportunistic Infection- illness due to an organism that causes disease in people
with weakened immune systems; commonly found in AIDS patients
• Asymptomatic stage- infection in which the infectious agent, such as HIV, is present
but there are few or no symptoms of the infection
Structure
• It is roughly spherical

• diameter of about 120 nm

• composed of two copies of positive-sense single-stranded RNA

• RNA codes for the virus's nine genes enclosed by a conical capsid composed of
2,000 copies of the viral protein p24
• RNA is tightly bound to nucleocapsid proteins- p7

• enzymes needed for the development of the virion such as reverse

transcriptase,
proteases, ribonuclease and integrase are also present.
• A matrix composed of the viral protein p17 surrounds the capsid ensuring
the integrity of the virion particle
• A lipid viral envelope is present that composed of proteins like gp41 and
gp120
Structure
• Classification - The International Committee on the Taxonomy of

• Viruses (ICTV) as two separate families — Papillomaviridae and Polyomaviridae.

• HPV is divided into High risk HPV and Low risk HPV. Low- risk types cause warts
and high-risk types can cause lesions or cancer.

• Pathogenesis

• HIV can infect immune cells such as CD4+ T cells, macrophages, and microglial cells.

• HIV-1 entry to macrophages and CD4+ T cells is mediated through interaction of the
virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells'
membrane also with chemokine co-receptors – CCR5
Multiplication
Multiplication steps

Entry:
• The virion enters cells by the adsorption of gp on its surface to receptors (CD4,
CCR5) on the target cell

• followed by fusion of the viral envelope with the target cell membrane

• the release of the HIV capsid into the cell

Replication and transcription:

• reverse transcriptase liberates the positive-sense single-stranded RNA genome
from the attached viral proteins and copies it into a complementary DNA (cDNA)
molecule

Assembly and Release:

• The final step of the viral cycle, assembly of new HIV-1 virions, begins at the
plasma membrane of the host cell.
Multiplication steps
• The classical process of infection of
a cell by a virion can be called
"cell-free

spread“

• In cell-free spread , virus particles

bud
from an infected T cell, enter the
blood or extracellular fluid and
then infect another T cell
following a chance encounter.
• HIV can also disseminate by cell-
to-cell spread,
• Three Phases of HIV

• Phase 1- Asymptomatic Stage

• Short, flu-like illness, swollen glands, fatigue, diarrhea, weight loss, or fevers -
occurs one to six weeks after infection

• no symptoms at all

• Infected person can infect other people

• Lasts for an average of ten years

• HIV antibodies are detectable in the blood

• Phase 2 – Symptomatic

• The symptoms worsen Mental changes, forgetfulness & abnormal thinking patterns

• Phase 3 - HIV  AIDS

• Immune system weakens

• Emergence of opportunistic infections and cancers

• The illnesses become more severe leading to an AIDS diagnosis

• Opportunistic Infections associated with AIDS

• Bacterial- Tuberculosis (TB), Pneumocystis pneumonia

• Viral- Kaposi Sarcoma-purple-red blotches on the skin, Influenza (flu)

Symptoms
Primary HIV infection

• often is mistaken for influenza or a bad cold - reported by roughly half of those
who contract HIV
• generally occurs between 2 and 6 weeks after infection

• Symptoms may include fever, headache, sore throat, fatigue, body aches, weight
loss, and swollen lymph nodes. Neurological symptoms of peripheral
neuropathy
• Other symptoms are a rash, mouth or genital ulcers, diarrhea, nausea and vomiting,
and
thrush. Gastrointestinal symptoms, such as vomiting or diarrhea may occur
• The CD4+ T cell count can drop very low during the early weeks
• The initial illness can last several days or even weeks.
• The greatest spread of HIV occurs throughout the body early in the disease.
 Symptoms
Latency period

• After initial infection comes the latency period, or incubation period

• period lasts a median of about 10 years.

• The most common symptom is lymphadenopathy, or swollen lymph

nodes.

• The lymph nodes of arms, neck, groin area

 Symptoms
Acquired immunodeficiency syndrome (AIDS)

• defined in terms of either a CD4+ T cell count below 200 cells per µL or
the occurrence of specific diseases in association with an HIV infection.

• develop AIDS within ten years.

• most common initial conditions are pneumocystis pneumonia, cachexia in

the form of HIV wasting syndrome, and esophageal candidiasis and
recurrent respiratory tract infections

• increased risk of developing various viral-induced cancers, including

Kaposi's sarcoma, Burkitt's lymphoma, primary central nervous system
lymphoma, and cervical cancer.
 Symptoms
Pulmonary
• Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii a yeast like
fungus
• Tuberculosis (TB)
Gastrointestinal
• Esophagitis is an inflammation of the lining of the lower end of the esophagus
• Unexplained chronic diarrhea (Salmonella, Shigella, Listeria or
Campylobacter)
Neurological
• Toxoplasmosis is a disease caused by the single-celled parasite called
Toxoplasma gondii
• demyelinating disease, in which the gradual destruction of the myelin
sheath covering the axons of nerve cells impairs the transmission of nerve
impulses (by JC virus)
• Dementia
Tumors
• Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients
• Lymphoma, cervical cancer, hepatocellular carcinoma
• Modes of HIV/AIDS Transmission

• Sexual transmission
• Through Bodily Fluids
Mother-to-Baby
Blood products • Before Birth
Semen • During Birth
• Postpartum
Vaginal fluids
• After the birth
Breast Milk

Through IV Drug Use

• Sharing Needles

• Without sterilization

• Increases the chances of contracting

HIV
 Transmission
• Only certain body fluids—blood, semen, pre-seminal fluid, rectal fluids,
vaginal fluids, and breast milk

• from a person who has HIV can transmit HIV.

• These fluids must come in contact with a mucous membrane or

damaged tissue

• or be directly injected into the bloodstream (from a needle or syringe)

for transmission to occur.

• Mucous membranes are found inside the rectum, vagina, penis, and
mouth.
 Transmission
Sharing injecting equipment:

sharing needles, syringes or other equipment used to prepare and inject drugs with
someone who
has HIV.

• Passed from mother-to-baby during pregnancy, childbirth and breastfeeding

a mother infected with HIV can pass the virus to her baby via her blood during
pregnancy and
birth, and through her breast milk when breastfeeding.

• Contaminated blood transfusions and organ/tissue transplants

receiving blood transfusions, blood products, or organ/tissue transplants that are

contaminated with HIV. This risk is extremely small because most countries test
blood products for HIV first.
Diagnosis: ELISA TEST
• An enzyme-linked immunosorbent assay (ELISA) is a test that uses enzymes and
colour changes to identify a substance

• It can be used to identify specific surface markers or metabolites

associated with particular diseases

• Different variations of the ELISA test exist, but one of the most common
protocols involves the sandwich method:

• Known monoclonal antibodies are

• affixed to wells in a plate (these are the 'capture antibodies')

• A sample to be tested is added to the wells and any antigens present will
bind to the appropriate capture antibody

• The plates are then washed to remove any unbound antigen

 Diagnosis: ELISA TEST
• A second set of monoclonal antibodies linked to

colour-changing enzymes are then added to the

wells

• These 'detection antibodies’ will bind to any

antigens captured, creating a sandwich (antibody

- antigen - antibody)

• The wells are then washed again to remove

any unbound detection antibodies

• When an appropriate substrate is added to the

wells, the enzyme-linked detection antibodies

will trigger a colour change

Diagnosis: ELISA TEST
 Diagnosis:
Common diagnosis methods are ELISA testing, but has to e confirmed by PCR

or NAT or Western blot

• ELISA testing

• Western blotting

• nucleic acid testing (NAT)

• Polymerase chain reaction

 Pre Exposure Prophylaxis

PrEP
PrEP is a single
daily pill of trivada PrEP does not
(drug combination prevent STIs or
of pregnancy. PrEP is
tenofovir/emtricitabi more effective when
ne) that can reduce it is combined with
is an option for all other prevention

90
risk of HIV by up to
genders who measures like
condoms
are HIV-negative
and at risk for
HIV
 Post Exposure
Prophylaxis

PEP
PEP means taking
antiretroviral
medicines (ART) PEP does not
after being prevent STIs or
potentially exposed pregnancy. You
to HIV to prevent should continue to
becoming infected is an option for all use condoms
genders who are
72hrs
with in with sex partners
HIV-negative and and safe injection
for practices while
at risk for HIV
taking PEP

28day
s
 Treatment
• Treatment consists of highly active antiretroviral therapy (HAART) which
slows

progression of the disease.

• Current HAART options are combinations consisting of at least three

medications belonging to at least two types of antiretroviral agents

• typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus

two nucleoside analog reverse transcriptase inhibitors (NRTIs).

• zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or

emtricitabine (FTC)

•
 Treatment
• Once treatment is begun it is recommended that it is continued without

breaks

• treatment with antiretrovirals reduces the risk of developing additional

opportunistic infections

• Dietary intake of micronutrients

• higher intake of vitamin A, zinc, and iron can produce adverse effects in

HIV positive adults, and is not recommended unless there is documented

deficiency
 Prevention

• Avoid multiple partners

• Don’t share needles, syringes, drug injection equipment, or any item
that may put a person in contact with blood
• Use condoms