PATHOPHYSIOLOGY OF

HIV AND AIDS

BY:
Dr Olasinde Abdulazeez Ayodeji
Department of Community Medicine
ABUTH Zaria.
OUTLINE
• PATHOPHYSIOLOGY OF HIV AND AIDS
• TYPES OF HIV
• LIFE CYCLE OF HIV
• NATURAL PROGRESSION OF HIV AND AIDS
• FACTORS AFFECTING HIV AND AIDS DISEASE PROGRESSION
PATHOPHYSIOLOGY OF HIV AND AIDS
• HIV produces cellular immune deficiency characterized by the depletion of helper T
lymphocytes (CD4+ cells). The loss of CD4+ cells results in the development of opportunistic
infections and neoplastic processes.
• After the virus enters the body there is a period of rapid viral replication, leading to an
abundance of virus in the peripheral blood. During primary infection, the level of HIV may
reach several million virus particles per milliliter of blood.
• This response is accompanied by a marked drop in the number of circulating CD4+ T cells.
The acute viremia is almost invariably associated with activation of CD8+ T cells, which kill
HIV-infected cells, and subsequently with antibody production, or seroconversion.
• The CD8+ T cell response is thought to be important in controlling virus levels, which peak
and then decline, as the CD4+ T cell counts recover.
• A good CD8+ T cell response has been linked to slower disease progression and a better
prognosis, though it does not eliminate the virus.
PATHOPHYSIOLOGY OF HIV AND AIDS
(contd.)
• Ultimately, HIV causes AIDS by depleting CD4+ T cells. This weakens the immune
system and allows opportunistic infections. T cells are essential to the immune
response and without them, the body cannot fight infections or kill cancerous cells.
• When the immune system is damaged enough that significant opportunistic
infections begin to develop, the person is considered to have AIDS.
• Although antibodies against HIV can be detected, it is clear that they are not
sufficiently neutralizing to assist with immunologic control of the infection.

• The role of NK (Natural Killer) cells may be important in the initial control of HIV.
Escape mutations have been detected, implying that immunologic pressure on HIV
exists from NK cells.
TYPES OF HIV
• HIV is a retrovirus that primarily infects components of the human immune
system such as CD4+ T cells, macrophages and dendritic cells.
• HIV is a member of the genus Lentivirus, and part of the family Retroviridae.
• Two types of HIV have been characterized: HIV-1 and HIV-2.
• HIV-1 is the virus that was originally discovered (and initially referred to also
as LAV or HTLV-III). It is more virulent, more infective, and is the cause of the
majority of HIV infections globally.
• The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer
people exposed to HIV-2 will be infected per exposure. Because of its
relatively poor capacity for transmission, HIV-2 is largely confined to West
Africa.
LIFE CYCLE OF HIV

SOURCE:https://www.niaid.nih.gov/
diseases-conditions/hiv-replication-cycle
LIFE CYCLE OF HIV (contd.)
• This infographic illustrates the HIV replication cycle, which begins when HIV fuses with the surface of
the host cell.
• A capsid containing the virus’s genome and proteins then enters the cell. The shell of the capsid
disintegrates and the HIV protein called reverse transcriptase transcribes the viral RNA into DNA.
• The viral DNA is transported across the nucleus, where the HIV protein integrase integrates the HIV
DNA into the host’s DNA. The host’s normal transcription machinery transcribes HIV DNA into multiple
copies of new HIV RNA. Some of this RNA becomes the genome of a new virus, while the cell uses
other copies of the RNA to make new HIV proteins.
• The new viral RNA and HIV proteins move to the surface of the cell, where a new, immature HIV
forms. Finally, the virus is released from the cell, and the HIV protein called protease cleaves newly
synthesized polyproteins to create a mature infectious virus.

• Credit
• NIAID
NATURAL PROGRESSION OF HIV AND
AIDS
• A typical HIV infection can be divided into three stages: primary infection,
asymptomatic infection, and symptomatic infection including AIDS.
• Following primary HIV infection, the CD4+ cell count decreases and the
HIV RNA rises significantly.
• At this point, the viral load is typically very high, and the CD4+ T-cell
count drops precipitously.
• With the appearance of anti-HIV antibodies (seroconversion) and CD8+ T-
cell responses, the viral load drops to a steady state and the CD4+ T-cell
count returns to levels within the reference range, although slightly
lower than before infection.
NATURAL PROGRESSION OF HIV AND
AIDS (contd.)
• Seroconversion may take a few weeks, up to several months.
Symptoms during this time may include fever, flulike illness,
lymphadenopathy, and rash. These manifestations develop in
approximately half of all people infected with HIV.
• This primary stage is sometimes referred to as Seroconversion stage
NATURAL PROGRESSION OF HIV AND
AIDS (contd.)
• At the Asymptomatic stage, persons infected with HIV exhibit few or
no signs or symptoms for a few years to a decade or more.
• Viral replication is clearly ongoing during this time, and the immune
response against the virus is effective and vigorous.
• In some patients, persistent generalized lymphadenopathy is an
outward sign of infection.
• During this time, the viral load, if untreated, tends to persist at a
relatively steady state, but the CD4+ T-cell count steadily declines.
NATURAL PROGRESSION OF HIV AND
AIDS (contd.)
• The asymptomatic stage which is sometimes referred to as Latency
stage or Latency period can last for 2 to 10 years or more even in the
absence of treatment.
• Evidence now shows that therapy initiation early in the asymptomatic
period is effective. However, very late initiation is known to result in a
less effective response to therapy and a lower level of immune
reconstitution.
NATURAL PROGRESSION OF HIV AND
AIDS (contd.)
• In the early symptomatic phase of AIDS, a number of opportunistic
infections, including oral candidiasis and tuberculosis are common.
• When the immune system is damaged enough that significant
opportunistic infections begin to develop, the person is considered to
have AIDS.
• In the later stages of symptomatic HIV infection, the viral load levels
rise again.
NATURAL PROGRESSION OF HIV AND
AIDS (contd.)

Timeline of CD4 T-cell and viral-load changes over time in untreated human immunodeficiency
virus (HIV) infection. Courtesy of Wikipedia (based on an original from Pantaleo et al (1993)).
FACTORS AFFECTING HIV AND AIDS
DISEASE PROGRESSION
• Viral factors:
1. Infective dose of the virus
2. Type of virus (HIV-1 or HIV-2)
3. Viral subtype
4. Viral mutation
5. Viral load
• Host factors:
1. Host genetic variation
2. The presence or absence of CCR5 Co-receptor
Individuals with mutations of co-receptors CXCR4 and CCR5 are protected
3. Route of infection