✓ In 1981 - US CDC published a report of a rare cancer and

lung infection that occurred in 41 previously healthy

homosexual men

Kaposi’s sarcoma Pneumocystis carinii pnuemonia

✓ By the end of 1981, there were 270 cases of
immunodeficiency in gay men

✓ 121 of these men had died

✓ The US CDC initially referred this diseases as

GRID
✓ The media nicknamed the diseases “GAY
PLAGUE”
✓ However, by 1982, there were reports of:

▪ First cases of Pneumocystis carinii pneumonia in people who inject drugs

▪ Immunosuppression among person with Hemophilia A
▪ 22 cases of unexplained immunodeficiency and opportunistic infections in infants
▪ A 20 month old white infant who required multiple blood transfusion had developed unexplained cellular
immunodeficiency and opportunistic infections
✓ In September 24, 1982, the CDC used the
term AIDS or Acquired Immunodeficiency
Syndrome and release the first case
definition of AIDS which is…

“A disease that is moderately predictive of a

defect in cell mediated immunity, occurring in
persons with no known cause for diminished
resistance to that disease.”
✓ In 1983….
▪ The disease was reported among female partners of men who
had the disease, suggesting it could be passed on via
heterosexual sex.

▪ These new case discoveries suggest that the disease either

sexually or through exposure to blood or blood products
✓ In 1983….
▪ Doctors at the Pasteur Institute in France reported the
discovery of a new retrovirus called Lymphadenopathy-
Associated Virus (LAV) that could be the cause of the
disease.
✓ Human Immunodeficiency Virus (HIV)
▪ Etiologic Agent of AIDS
▪ Has 2 types
• HIV 1 – identified by the laboratories of Luc Montagnier of France and Robert Gallo and Jay Levy
of USA in 1983 and 1984, respectively.
➢ Formerly known as HTLV-III, LAV, ARV
➢ Has three groups: MNO
➢ M – responsible for HIV infections worldwide

• HIV-2 discovered in 1986. It causes majority of HIV infections in West Africa and in other parts of
the world
➢ Less pathogenic
➢ Lower rate of transmission
Body fluids considered to be infectious…
✓ Composition of the Virus

▪ Family – Retroviridae
▪ Genus – Lentivirinae
▪ A retrovirus -contains the enzyme reverse
transcriptase
▪ Genome -2 copies of ssRNA
▪ Spherical – 100 to 120 nm
✓ Parts of the virion

▪ Outer HIV envelope – made up of glycoproteins embedded in

the lipid bilayer
• Glycoproteins –knob like structure used by the virus to bind
to host cells
▪ HIV capsid or protein coat- encloses the inner core containing
the two copies of ssRNA
▪ Inner core – contains the genome (ssRNA)
✓ HIV Genome
✓ Viral Tropism
▪ Infects cells that express CD4 molecule (CD4+ cells)
• T helper cells – T tropic/X4 strain
• Other cells such as:
➢ Macrophages
➢ Monocytes – M tropic/R5 strain
➢ Dendritic cells
➢ Langerhans cells
➢ Microglial cells
✓ HIV Attachment to target cell
▪ First step in the replication
• gp 120 – attaches to the CD4 receptor on target
cell
✓ Chemokine receptors
▪ CXCR4 – required for HIV to enter lymphocytes
▪ CCR5 – required for HIV to enter macrophages
✓ Chemokine receptors
▪ Binding of HIV to these chemokine
receptors induces a conformational
change in the gp41 which mediates
fusion of the virus to the cell membrane
▪ After fusion, viral particle is taken into the cell,
and uncoating of the particle exposes the viral
genome.
▪ Complementary DNA is produced using HIV RNA
as template with the action of reverse
transcriptase enzyme.
▪ HIV DNA is integrated into the host’s DNA by the enzyme
integrase

▪ This becomes the provirus of HIV and can hide within the host’s
DNA for a long time resulting in latency
• No active replication
• Expression of viral genes is induced when:
➢ Infected cell is activated by binding with the antigen
➢ Activated by cytokines
▪ HIV DNA is transcribed to:
• Genomic RNA Transported in the cytoplasm
• mRNA
✓ Translation and release of newly formed
virions
▪ Production of viral proteins and assembly of
particles
▪ Intact virions bud out from the host cell
membrane and acquire their envelope
▪ Newly formed virions can proceed to infect
additional target cells
✓ Points to remember

▪ HIV replicates rapidly

▪ Reverse transcriptase lacks proof reading ability
which could result in genetic mutations
➢ New virions formed exhibit extraordinary level
of antigenic variations
➢ It hinders the host to mount an effective
immune response
✓ P24 antigen and viral RNA –increases in the serum during
replication
✓ Some viral proteins produced during replication forms
complexes with MHC class I of infected cells and generate
an immune response
✓ HIV specific CD T helper cells – assist in humoral and cell
mediated immune response
✓ B-cells stimulated to produce antibodies
▪ Antibodies against the gp41 antigen- the first to be
detected
▪ P24 antibodies, and other antibodies to HIV antigens
▪ Envelope protiens– most immunogenic, and can trigger
synthesis of neutralizing antibodies.
HIV Immune response
✓ CTL and antibody responses – hindered by the rapid
mutations of HIV
▪ Escape mutants
✓ HIV downregulates expression of MHC class I
✓ Can be harbored as silent provirus in numerous cells
▪ Resting CD4 T cells
▪ Dendritic Cells
▪ Monocytes- Macrophage system
▪ Microglial cells
✓ Decrease in CD4 T cells – hallmark of HIV infection. Killed
through the following mechanisms:
▪ Loss of plasma membrane integrity during viral budding
▪ Destruction by HIV specific CTL
▪ Viral induction of apoptosis
HIV Immune response
 ✓ Effects of CD4 T cell destruction

▪ Decrease in both antibody and cell-mediated immune response

• Affects not only the immune response to HIV but also to a broad range of antigens
encountered by the host.
▪ Dysregulated immune response – HIV proteins cause polyclonal activation of B cells
▪ B cells – have reduced ability to mount antibody response against HIV due to lack of T cell
help.
▪ Decline in CTL function and delayed hypersensitivity response to antigens
▪ Altered production of cytokines
▪ Extensive damage to lymphoid tissues
▪ Defective antigen presentation and generation of oxidative burst , decrease NK cell activity
✓ Acute or early stage of HIV Infection
▪ Rapid burst of viral replication before the development
of HIV specific symptoms
▪ Viremia – resulting in HIV spreading in the lymphoid
organs.
▪ Transient reduction of CD4 count
▪ Typical manifestation: Acute Retroviral Syndrome “flu-
like or mononucleosis like” symptoms.
▪ Appears 3-6 weeks after initial infection, resolves after
7 weeks
▪ Note: Many are asymptomatic
✓ Latent State
▪ Occurs as HIV-specific immune develops that curtail
replication
▪ Decrease viremia
▪ Subtle, or absent clinical symptoms
▪ CD4 T cell count – stable for a period in time then will
start to decline
▪ Asymptomatic for 10 years – long term nonprogressors
(LNTP) individuals
• Normal or mildly depressed CD4 count
• Low viral loads
✓ AIDS Stage
▪ Final stage of HIV infection
• Profound immunosuppression
• Very low CD4 T cell counts
• Resurgence of viremia
• Life threatening opportunistic infections and malignancies, neurological symptoms
• Occurs in untreated indivuals usually 10 years after initial infection.
✓ AIDS Stage

Kaposi Sarcoma caused by HHV-8 Pneumonia caused by

Pneumocystis jerovicii (carinii)
✓ AIDS Stage

Oral and Vaginal thrush caused by Candida albicans

✓ Sexual abstinence is 100% guaranteed effective in preventing
HIV infection

✓ Safe sex practices

✓ Screening of blood donors ✓ Avoidance of needle sharing among IV drug users
✓ Supportive care to the associated infections and
malignancies
✓ Administration of antiretroviral therapy (ARV)
▪ Combination anti-retroviral therapy (CART)
▪ Highly Active anti-retroviral therapy (HAART)
✓ Screening Tests
▪ ELISA
▪ CLIA
▪ Immunochromatographic Assay (Lateral Flow)
✓ Confirmatory Test
▪ Western Blot Assay- Standard confirmatory test

✓ Newer testing methods

▪ Serological tests to detect HIV p24 antigen For earlier and more accurate detection
▪ Serological test to detect HIV RNA
✓ Serologic Picture

▪ Window period
▪ Seroconversion
✓ Western Blot Test
Principle
▪ Partially purified HIV virus is inactivated, and the HIV
antigens (shown on the left picture) are fractionated
according to their molecular weight.

▪ Known analyte: HIV antigens

▪ Unknown analyte: anti-HIV antibodies in patient’s serum
▪ Labeled analyte:: Labeled secondary antihuman globulins
✓ Western Blot Test
✓ Western Blot Test
Result:
▪ Binding of HIV antibodies to HIV antigens found on the strip
bands corresponding to the position of the antigens in the
strip will be formed indicating that antigen-antibody
reaction has occurred
Interpretation:
▪ Positive result:
• Bands present in at least two of the following:
₋ P24, gp41, gp120/gp160
▪ Negative result:
₋ No bands formed
▪ Indeterminate:
₋ Bands that do not meet the criteria for a positive
result
Stevens, C. D., & Miller, L. E. (2016). Clinical Immunology and Serology: A Laboratory
Perspective. FA Davis.