HIV is a retrovirus that infects CD4+ T cells and causes AIDS by destroying the immune system. It enters the body through sexual contact, blood transmission, or during birth. Once inside it spreads to lymphoid tissues where it replicates within T cells and macrophages. This causes cell dysfunction and death, damaging the immune system over time. Despite an immune response, HIV evolves rapidly and establishes reservoirs that allow lifelong persistence. Without treatment, this progressive immune destruction ultimately results in AIDS.

1. HIV/AIDS
DR NGANDALO
MED 2,1

2. 2
The Human Immunodeficiency Virus (HIV)
• A retrovirus from the Lentivirus family.
• Genetic material consists of a single-stranded ribonucleic acid
(RNA)
• Viral particle is spherical in shape with a diameter of 80-100
nanometers (nm).

3. 3
THE BIOLOGY OF THE HUMAN
IMMUNODEFICIENCY VIRUS
There are two types of HIV
• HIV – 1
– Is found worldwide
– Is the main cause of
the worldwide
pandemic
• HIV – 2
– Is mainly found in West
Africa, Mozambique and
Angola.
– Causes a similar illness
to HIV – 1
– Less efficiently
transmissible rarely
causing vertical
transmission
– Less aggressive with
slower disease
progression

4. 4
HIV-1 SUBTYPES
• HIV-1 has many subtypes: A-K
• A-E are the predominant subtypes
– A: West Africa, E. Africa, Central Africa East Europe
& Middle East
– B: North America, Europe, Middle East, E. Asia, Latin
America
– C: Southern Africa, S. Asia, Ethiopia
– D: East Africa
– E: South East Asia

5. 5
HIV SUBTYPE C
• This is the most virulent (aggressive) subtype.
• It has a higher replication rate.
• Is associated with faster disease progression in
adults.

7. 7
STRUCTURE OF HUMAN IMMUNODEFICIENCY
VIRUS
 Has an outer double lipid
membrane (viral envelope)
 The lipid membrane is lined by
a matrix protein (p17).
 The lipid membrane is studded
with the surface glycoprotein
gp120 and the transmembrane
glycoprotein gp41.
 These glycoprotein spikes
surround the cone-shaped
protein core (p24).
 The protein core contains
genetic material (RNA) and
viral enzymes (protease and
reverse transcriptase)

8. Why is AIDS a unique viral disease?
• It is caused by viruses unknown before
1983 - retroviruses human
immunodeficiency virus 1 and 2 (HIV1
and HIV 2)
• Its a collection of clinical illnesses
(opportunistic infections and
malignancies) resulting from the
destruction of the immune system
• It develops as a result of HIV infection
that occurred many years previously (on
average 10 years) and that is continuous
in its progression

9. 90-90-90
• An ambitious treatment target to help end
the AIDS epidemic
• By 2020, 90% of all people living wth HIV
will knw their HIV status
• By 2020, 90% of all people with diagnosed
HIV infection will receive sustained
antiretroviral therapy
• By 2020, 90% of all people receiving ART
will have viral suppression

10. Diagnosis
HIV Testing Services (HTS)
• Refers to full range of services that should be provided
wth HIV testing includig counceling
Universal Routine HIV Testing
• Test and treat regardless of CD4 count
HIV Self-Testing (HIV-ST)
• Refer to HIV protocal 2018

11. Diagnostic Tests for HIV
Detection of the causative agent
• Complete virion
– Virus culture in clinical specimens:
• Inoculation of lymphocytes from a infected
person on specific cell lines, difficult in early
infection
– Electron microscopy:
• Cultured virus can be seen under EM but not
very practical
• Virus components
– Antigen tests:
• P24 antigen is viral core protein. Its presence
in the serum denotes active replication but it
is not detected in all patients
– Nucleic acid detection:
• PCR to identify HIV RNA. Can detect early
infection but very expensive.

12. Diagnostic Tests for HIV
Detection of the immune response to the pathogen
• Antibody detection tests
– a positive antibody test signifies current
infection
– Specific antibodies generally appear 6-12
weeks after infection
– Commonly used methods:
• Rapid tests: Used as screening tests but
possibility of false positives means
confirmatory testing of positives with a
more specific test is needed
• ELISA
• Western Blot
– False negative tests
• 0-6 weeks – window period
• Terminal phases of disease due to severe
B cell dysfunction
– Occasional discrepant results due to
• non-specific cross-reactivity
• early infection
Repeat test after 3-4 months or do PCR test

13. 1~3 m 2-3~10 years 1~3 years
Acute Asymptomatic ARC AIDS
Progression to AIDS
HIV
HIV
CD4+
Anti-p24
Anti-gp160/120 Anti-gp41

14. Encounter and Entry
• Transmitted by direct inoculation of infected blood or body fluids into the host
– Sex: spread of disease facilitated by
• Sexual practices associated with trauma eg receptive anal sex, dry sex
• Other STDs especially genital ulcers like chancroid (epithelial barrier
breached)
• Promiscuity. Rate of HIV transmission with sex is lower than with other STDs
~ 0.3% per sexual contact with an infected person. However, some become
infected after a single sexual contact, while others remain uninfected after
hundreds of contacts.
– Blood:
• Blood transfusions
• IV drug users
• Risky occupations: Health care workers (1 in 300 needlestick injuries)
– Birth: 15-30% of infants contract the disease by vertical transmission
• depends on maternal immune responses
• levels of HIV circulating in the mothers blood
• HIV in saliva, urine, tears, and sweat is of no clinical importance. Transmission
through these fluids does not routinely occur, because of low concentration of virus.

15. Other entry routes
• There is no evidence to suggest that HIV can be transmitted by:
– Insects
– Casual contact, saliva, kissing
– Sharing of eating and drinking utensils
• If HIV were being transmitted through other routes (such as through air, water, or
insects), the pattern of reported AIDS cases would be much different from what has
been observed.

16. Factors Contributing to the Spread of HIV in Zambia
• Prevalence of other STDs
• Multiple sexual relationships
• Low use of condoms
• Lack of male circumcision
• Poverty and poor overall health
• Low status of women
• Urbanization and mobility
• Early sexual activity
• Cultural practices
sexual contact
mother to child
other

17. Pathogenesis of HIV
(How does infection with the human immuno-deficiency virus
result in the disease AIDS? )

18. 18
Components of the immune system
• Non-specific
immunity
– Natural barriers to
infection
– Phagocytosis:
neutrophils,
macrophages
• Specific immune
system
– Cellular immunity: T
lymphocytes
– Humoral: B lymphocytes
and antibodies

19. 19
The cells with CD4 receptors are the
primary targets for HIV.
– T-Lymphocytes – helper
– Macrophages
– Monocytes
– Other receptors needed are CCR5

20. 20
HIV LIFE CYCLE
Stages of the life
cycle
 Binding, Fusion and
Entry
 Transcription
 Integration &
Replication
 Budding
 Maturation

21. Outcome of HIV infection of a cell
Cell dysfunction and death.
• Actual mechanisms unclear but
various possibilities:
– HIV makes toxic protein not made
by other viruses?
– Build-up of unintegrated HIV DNA
which disrupts cellular
biosynthesis?
– Infected lymphocytes undergo
premature differentiation and
“senility”?
– T-helper cells inactivated by loss
of CD4 from the cell surface?
Virus Reservoir
• The virus multiplication cycle can
involve a latent phase in which
infected cells contain provirus but do
not produce new virus
• HIV proviruses contain signals that can
switch on virus multiplication again
when HIV-infected cells are stimulated
• A pool of latently-infected resting
CD4+ T-cells is established in primary
infection
• Early antiretroviral therapy fails to
prevent the establishment of the
latently-infected pool of cells

22. How does the virus spread from the site of entry to the rest of the body?
• After initial entry of HIV and establishment
of infection, replication occurs within
inflammatory cells at site of infection, or
within peripheral blood mononuclear cells
(PBMCs)
• Dendritic cells and macrophages in epithelia
such as in genital tract can be infected by
HIV but not destroyed. They carry HIV
elsewhere in the body
• Then the major site of replication shifts to
lymphoid tissues including lymph nodes,
spleen, liver, and bone marrow
• Follicular dendritic cells (FDC) in lymphoid
tissues also trap virus in their processes
and may infect CD4 cells passing through
the nodes – the FDC themselves not being
destroyed
HIV, once it enters the body, is carried to the
lymphoid tissues where both CD4+ T-
lymphocytes as well as follicular dendritic
cells can become infected.

23. How does the virus damage infected cells and the immune system?
• Unclear but it is thought by:
– Direct lysis of infected cells: Viral
replication kills many of the infected cells.
– Indirect killing by cytotoxic T lymphocyte
recognition of infected cells
– Syncytium formation: Dying cells
expressing viral envelope proteins, can
bind to CD4 receptors on other cells,
resulting in cell-to-cell aggregation, fusion
and formation of large multinucleated
syncytia
– Infection of precursor cells and destruction
of microenvironment

24. How is HIV able to survive despite host’s immune response?
• The body mounts a specific immune response to the virus which results in initial
lowering of viral load.
– Antibody
– Cell mediated immunity
• Despite this, HIV infection is unique in its failure to resolve infection
• Several mechanisms may explain this:
– relative invisibility of virus gene products to the immune response in reservoir
cells
– progressive damage and destruction of cells that are supposed to mount this
immune response
– the virus may be able to mask or change its antigenic specificity - antigenic
variation

25. Progression of Infection
• Primary HIV infection starts with a burst of
viremia and dissemination of infection
with virus detectable in PBMCs and
plasma.
• This is followed by a period of clinical
latency, with little detectable virus in the
blood, but viral replication actively
continuing in lymphoid tissues
• Infection with HIV is sustained through
continuous viral replication with re-
infection of additional host cells
• Persistent viremia is due to continuous re-
infection of new CD4 cells followed by
viral replication and infected host cell
turnover
• This rapid turnover of HIV and CD4 cells
promotes emergence of new strains of
HIV within the host resulting from
mutation of HIV

26. Refractoriness to HIV infection (slow progression)
Host Factors Donor Factors
Genetic Immunologic
•Neutralizing antibodies
•Cytotoxic CD8 T cells
•Strong mucosal immunity
•homozygous
delta 32 deficiency
CCR5 gene
•HLA haplotype
•Low viral load
•Less pathogenic virus

27. Viral factors contributing to pathogenicity
• HIV has ability to mutate easily – due
to error rate of the reverse
transcriptase enzyme
• High mutation rate leads to emergence
of HIV variants within infected
individual’s cells:
– that can resist immune attack
– that are more cytotoxic
– that can generate syncytia more
easily
– that can resist drug therapy
– that cause new pathologic lesions
as different cell types are targeted
eg "neurotropic" or
"lymphocytotropic" variants
• Over time, different tissues of the same
body may harbour differing HIV
variants

28. Clinical consequences of HIV damage

29. Primary HIV infection Acute HIV syndrome
HIV-specific immune response
Clinical latency
Clinically apparent disease/
AIDS defining illness
Death from AIDS
3-6wks
2 yrs
10yrs,median
1-2wks
1wk-3mo
Progression of HIV infection

30. Primary HIV Infection (acute infection syndrome)
• Primary HIV infection may go unnoticed in at least half of cases or produce
a mild disease which quickly subsides, followed by a long clinical "latent"
period lasting years.
• Fever, lymphadenopathy, pharyngitis, diffuse erythematous rash,
arthralgia/myalgia, diarrhea, and headache are the commonest symptoms
seen with acute HIV infection.
• Symptomatic acute HIV infection is more likely in persons infected through
sexual transmission.
• The immune response is accompanied by a simultaneous decline in HIV
viremia.
• The CD4 lymphocytes rebound in number, but not to pre-infection levels.
• Seroconversion with detectable HIV antibody by laboratory testing
accompanies this immune response.

31. Clinical Latency
• AIDS has a very long latent period before the development of signs of infection.
• During this phase, there is little or no viral replication detectable in peripheral blood
mononuclear cells and little or no virus in peripheral blood. The CD4 lymphocyte
count remains moderately decreased.
• However, the immune response to HIV is insufficient to prevent viral replication within
lymphoid tissues.
• Tests for HIV antibody will remain positive during this time. There is no evidence to
suggest that sero-reversion, or loss of antibody, ever occurs.
• The HIV-infected person may live up to 8 or 10 years, on average, before
development of the clinical signs and symptoms of AIDS.
• Persons infected with HIV cannot be recognized by appearance alone.
• At least 10% of persons infected with HIV-1 are "long survivors" who have not had
significant progressive decline in immune function.
• The development of signs and symptoms of AIDS typically parallels laboratory testing
for CD4 lymphocytes. A decrease in the total CD4 count below 500/microliter
presages the development of clinical symptoms

32. Prodromal phase
• This period involves the insidious onset of a variety of prodromal disorders,
including:
– Persistent Generalized Lymphadenopathy (PGL) - There is loss of
normal lymph node architecture as the immune system fails. Lymph
nodes throughout the body are enlarged.
– Constitutional symptoms - weight loss, fever, skin rashes
– Early opportunistic infections - oral candidiasis and diarrhoea.
Fig. 5.2: Oro-pharyngeal candidiasis in an HIV positive person

33. Clinical AIDS
• The stage of clinical AIDS is defined as the
appearance of one or more of the typical
opportunistic infections or neoplasms
diagnostic of AIDS.
• Syndrome with the following features:
– Marked Constitutional disease: fever,
diarrhoea, weight loss, skin rashes
– Neurological disease: dementia,
myelopathy, peripheral neuropathy
– Immunodeficiency: Increased susceptibility
to opportunistic infections
– Rare malignancies: Kaposi sarcoma, oral
hairy leukoplakia, lymphomas.

34. Kaposi's sarcoma typically produces one or
more reddish purple nodules on the skin, as
seen here grossly.
Visceral involvement with Kaposi's sarcoma in
AIDS is common. Here are multiple reddish
nodules seen over the gastric mucosa.
Kaposi sarcoma - is a tumor of endothelial cells. Prior to the AIDS epidemic,
this tumor was rare and only found in middle aged African and Mediterranean
Jewish men, in whom it was an indolent condition. AIDS patients develop a
disseminated highly aggressive form of the disease.

35. Oral hairy leukoplakia: White
vertically oriented corrugated
plaques on the side of the tongue
are typical and very suggestive of
HIV infection. Epstein Bar Virus is
the pathogen.

36. Cut sections of this enlarged lymph node
involved with high-grade non-Hodgkin's
lymphoma in AIDS reveal a "strawberry
sundae" appearance with swirls and globs
of red in white. This can also be seen with
extra-nodal AIDS lymphomas
Malignant lymphoma is typically
extranodal in AIDS. Seen here in
small intestine are two mass
lesions on the mucosal surface.