HIV ppt.ppt.............................

KJ

1. Pathogenesis of HIV disease
and markers of progression

2. ORIGIN OF HIV
•Research teams in the USA & France made independent research
discoveries of the virus
•French researchers discovered a virus linked to AIDS in 1983, they
called it Lymphadenopathy Associated Virus (LAV)
•In 1984: American researchers isolated a virus that caused AIDS, calling
it Human T-lymph tropic Virus III ( HTLV-III)
• These 2 viruses were later found to be the same virus- HIV
•The emergence of HIV & AIDS has resulted in countless debates as to
where it originated from

3. Introduction
•HIV (Human immunodeficiency virus) is a retrovirus that causes Acquired Immune
Deficiency Syndrome (AIDS).
•It attacks and destroys white blood cells, causing a defect in the immune system.
• The outer layer of the HIV virus cell is covered in coat
proteins, which can bind to WBCs. This allows the virus to
enter the cell, where it alters the DNA.
•HIV specifically attacks the CD4 cells (T cells) which are critical to the body’s
immune response: If untreated it reduces the number of CD4 cells in the body,
making a person more likely to get other infections .
•Has 2 strains: HIV-1 and HIV-2

4. Epidemiology
•The estimated overall HIV prevalence rate was approximately 12,6% among
the South African population. The total number of people living with HIV
was estimated at approximately 7,06 million in 2017. For adults aged 15–49
years, an estimated 18,0% of the population was HIV positive
(StatsSA ,2017).
•One study showed a 50% reduction in morbidity and mortality in those who
initiated ART versus those who did not. The overall outcome however
depended on the level of immunodeficiency, as indicated by CD4 count at
the time of treatment initiation.
• Worldwide, the predominant virus is HIV-1, with HIV-2 type concentrated in
West Africa and rarely elsewhere
•HIV-1 is more pathogenic and HIV-2 is less pathogenic

5. Epidemiology cont.…
•Reservoir of infection:
• Humans are the reservoirs for virus
•Source of infection:
»Highest concentration is on Blood, Semen
»Lower concentrations are on tears, saliva and urine
•Higher risk groups:
– Prostitutes
–Transfusion recipient of blood and blood products
–Male homosexual and bisexual
–Intravenous drug abuser

6. The acute phase of replication
1.Massive replication occurs in gut lymphoid
tissue
2.CD4
+
CCR5
+
memory T-cells are main targets
for infection
3.Replication spills out into lymph nodes and
blood
From Brenchley et al. JEM 200,
749-759
The ileum before and after HIV
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7. Overview of HIV life cycle
HIV life cycle:
1.Binding and Fusion
2.Entry
3.Reverse transcription
4.Integration
5.Viral RNA and protein expression
6.Assembly and budding
7.Maturation
HIV target cells:
CD4T cells,
Macrophages,
Dendritic cells

8. Diagnosis
•Three types of tests:
• Screening tests: ELISA and simple/rapid tests
• Confirmatory or supplemental test: Western Blot
assay
• Nucleic acid and antigen screening tests: PCR
(Polymerase Chain Reaction), Nucleic acid based
Sequence assays (NABSA).

10. DRUG RESISTANCE
•The highly mutable nature of HIV has led to a number of virus mutations that have
decreased or negated the efficacy of some antiretroviral drugs (Patarca et al., 2003).
•The primary cause of drug resistance is the lack of regimen adherence of patients
who are on HAART.
•Genotypic assays are available to detect drug resistance mutations when present in
HIV genes.
•Resistant strains of HIV can be transferred from people who have been treated with
antiretroviral to treatment naive individuals, so concerns about drug resistance are
salient not only for the treatment exposed but also for the newly infected and for
those who are new to drug therapy (Patarca et al., 2003).
•A missed weekend of medications can result in drug resistance (Patarca et al., 2003).

11. HIV disease progression –
clinical latency
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CD4+ T cell
HIV viral load
CD8+ T cell
Neutralizing Antibodies
Years
AIDS and
Death
Acute Asymptomatic
(clinical latency)
4 – 8
weeks
Primary
infection

12. HIV disease progression
–Acute infection
Primary infection of cells in blood or
mucosa (HIV directly infects T cells and
microphages oris carried to those cells
by dendritic cells)
Viral replication in the regional lymph
nodes leads to Exponential viral
growth and widespread dissemination
Development of anti-viral responses
and symptoms of acute infection occur
Decrease in plasma viral load and
symptoms of acute infection resolve

13. HIV disease progression --
Clinical Latency
•During this period of the disease, the
immune systems remains competent at
handling most infections with
opportunistic microbes
•Few or no clinical manifestation.
•Steady destruction of CD4+ T cells
and steady decline of circulating
blood CD4+ T cells

14. Mechanism of CD4 T cell depletion in HIV
infection

15. Mechanism of CD4 T cell depletion in HIV
infection
•Infection and killing of infected cells only explain part of the T cells
loss
•Chronic immune activation and disrupted T cell homeostasis

16. Stem Cell
Mature
T-Cells
HIV Infected Cells
HIV-Specific
T Cell
Expansion of
HIV-Specific
Cells
Killing of HIV
Infected Cells
Incomplete Clearance
of HIV Infected Cells
and Exhaustion
HIV Specific T Cell Responses
Thymus Periphery
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17. HIV disease progression --
AIDS
•Acquired Immune Deficiency Syndrome:
•Catastrophic breakdown of host
defenses, marked increase in viremia
and clinical disease.
•CD4+ cell count less than or equal to
200 per microliter
•Clinical Features:
•Opportunistic infection
•Neoplasms
•CNS involvement

18. HIV disease progression –
clinical latency
L
e
v
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l
s

(
S
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p
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r
a
t
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S
c
a
l
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)
CD4+ T cell
HIV viral load
CD8+ T cell
Neutralizing Antibodies
Years
AIDS and
Death
Acute Asymptomatic
(clinical latency)
4 – 8
weeks
Primary
infection

19. Markers of HIV disease progression
•CD4 T cell counts
•Viral load
•Markers of immune activation

20. Markers of disease progression: CD4 cell
count
•Major Factor to initiate therapy
–CD4<350: strongly recommended (Data from randomized trials)
–<350<CD4<500: strongly recommended (Data from well designed non-
redomized trials or observational cohort studies)
–Cd4>500: moderately recommended
•Prophylaxis against opportunistic infection is based on CD4 counts
The Lancet Volume 360, Issue 9327 2002 119 - 129

21. Markers of disease progression: Viral load
•The HIV-1 viral load measurement indicates the number of
copies of HIV-1 RNA per milliliter of plasma.
•Viral load is an accurate reflection of the burden of infection
and the magnitude of viral replication.
•It is critical in monitoring virologic response to ART.
The Lancet Volume 360, Issue 9327 2002 119 - 129

22. Markers of disease progression: Viral load set
point