Natural History and Pathophysiology of HIV Infection

1
Natural History and Patho-physiology of HIV
Infection

• Dr Hannah Kibuuka

2
Definitions

• Natural history of HIV is the course of HIV when
  left untreated ( Using ARVs)
• Pathopysiology of HIV infection are the changes
  in body function associated with HIV infection

3
Session objectives

• Why the HIV epidemic
• What is the natural history of HIV infection
• Better understanding of management of HIV
• Why ARVs are not given to every body
• Why might HIV patients be required to take
  multiple drugs

4
Outline

• Introduction
• Transmission of HIV
• Natural history
• How HIV causes disease and what body changes
  occur in HIV infection
• Counseling tips

5
Introduction
6
Uganda

• More than 800,000 HIV adults and children
  infected by 20004
• Sero-behavioral survey 2004-2005
• Overall 6.4 adults
• F (7.9) and M (6)
• Urban(10.7) gt rural (6.4)
• Kampala (9)

7
HIV transmission and risk factors(1)

• Transmission of HIV
• Fluids commonly associated with transmission of
  HIV
• Vaginal fluids
• Semen
• Blood and blood components
• Breast milk
• Behavioral risk factors
• Sexual intercourse whether vaginal, anal or oral
• Number of sexual partners
• Intercourse with HIV infected
• Unprotected sex( lack of use of barrier
  precautions)
• Presence of STI
• Influence of alcohol and other substances that
  impairs decision making

8
Transmission and risk factors(2)

• Exposure to blood and blood products
• IV drug users
• Improperly screened blood and blood products
• Congenital exposure
• Exposure in pregnancy, labour and breast feeding

9
Once HIV enters the body..
Few days
Mucosal tissue
Lymph glands
Blood spread
Blood stream
Filtered in lymph glands
10
Acute HIV infection

• Due to initial infection and dissemination
  through out the body and occurs 1-4 weeks after
  exposure
• Common symptoms Headache, fever, rash,
  sorethroat, tiredness, muscle pain, enlarged
  lymph glands.
• Usually lt14 days but may be weeks or months.
• Non specific and could easily pass for common
  viral infections
• Others Nausea, vomiting, diarrhea, weight loss
  and acute psychological problems like
  irritability and confusion
• Amount of virus in blood and genital secretions
  is so high. This is when most people are
  contagious
• Occurs in 70 of individuals

11
Acute HIV infection

• May last from one to three weeks
• Those whose fever lasts over 2 weeks are more
  likely to have HIV infection that progresses
  rapidly
• The usual HIV test that detects antibodies will
  be negative at this time
• Highly infectious due to high level of HIV in
  blood and genital secretions
• People recover from acute HIV infection because
  of the bodys defense system
• Recovery is accompanied by disappearance of
  symptoms and a sharp decrease in viral load

12
Sero-conversion

• Body takes a few days to weeks to recognize a
  foreign substance like a virus
• Once substance is recognized, body produces
  antibodies that attack it
• For HIV, 6-12 weeks after the virus has entered
  the body, antibodies are in sufficient quantities
  to be detected by the usual tests
• gt95 people have positive tests by 3 months while
  gt99 of people have positive tests by 6 months
• In most infections once antibodies and other
  protective cells appear, organisms are eliminated
  but not so with HIV

13
Asymptomatic HIV infection

• For several years after one is HIV antibody test
  positive, People with HIV infection feel good. No
  clinical signs or symptoms
• Person unaware of HIV infection unless tested
• About 70-80 of people who are presently infected
  with HIV are in this asymptomatic phase
• HIV continues reproducing every day making new
  viruses and destroying bodys defenses.
• The body continues to produce new CD4s to offset
  the loss
• Virus in the blood remain low and constant for
  many years
• Eventually the body cant quite keep up and with
  time progressive depletion of CD4 occur
• The duration of this stage depends on how
  effective the bodys defenses were able to
  control the initial infection and therefore the
  amount of virus in blood(8-10 years)
• Period is longer the earlier the age at time of
  initial infection

14
Counseling tips!

• Negative HIV antibody test despite HIV infection
• Repeat HIV test after 3-6 months in those with
  initial negative test
• Can not determine HIV infection status based on
  clinical symptoms only.
• Some have no signs of illness
• Should have HIV testing

15
Symptomatic HIV disease

• Early symptomatic HIV disease
• Declining CD4
• Increasing virus in blood
• Symptoms include Fever, unexplained weight loss,
  recurrent diarrhea, headache, tiredness and skin
  problems
• Late symptomatic HIV disease (AIDS)
• Defense system is sufficiently compromised, the
  patient is unable to control other infections
  leading to opportunistic infections and cancers
• Without treatment the patient on average dies
  within 1-3 years
• Signs and symptoms typically parallels
  laboratory testing of CD4 counts
• Individuals could have very low CD4 without
  symptoms
• Risk of death from HIV infection with CD4 counts
  above 200 is low

16
Progression to AIDS

• Typical progressors 8-10 years asymptomatic HIV
  before developing AIDS
• Fall in viremia following acute infection
• Rapid progressors
• Develop AIDS in 2-3 years following initial
  infection
• High viral load during acute infection and levels
  do not fall to those of typical progressors
• Non progressors long survivors
• Relatively stable immune function for more that
  10 years. Stable CD4
• Low viral burden

17
Factors influencing the time course to
progression to AIDS

• Acute infection is symptomatic
• Viral strain
• Higher viral set point
• Older age at sero conversion
• Opportunistic infection or neoplasm present
• In Mother to child, signs of infection at
  lt3months

18
Death
Primary infection
Acute infection
Opportunistic diseases
Asymptomatic infection
Symptoms
19
Clinical staging based on Natural history

• WHO staging into IV stages
• Stage I Asymptomatic and has normal activity
• Stage II Symptomatic with weight loss, minor
  skin problems, Herpes zooster
• Stage III unexplained chronic diarrhea,
  unexplained prolonged fever, PTB Usually bed
  ridden lt 50 of the day during last month
• Stage IV Opportunistic infection eg PCP,
  Cryptococcal meningitis, Toxoplasma infection of
  brain etc. Usually bed ridden gt 50 of the day
  during last month

20
Counseling tips!

• Not every body that is diagnosed with HIV need to
  start ARVs immediately
• In absence of blood tests, a medical worker can
  start ARVs based on clinical staging
• Not every body who has HIV infection has AIDS.
• Even when diagnosed with HIV, one could still
  have beneficial life
• Once diagnosed HIV, regular medical monitoring is
  essential

21
HOW DOES HIV CAUSE DISEASE?
22
Immune system ( Bodys defense system)

• 2 main arms of the immune system.
• Antibody-mediated immunity
• Antibodies attack free organism in blood or
  lymph
• Cell-mediated defense system
• T-lymphocytes which attack and destroy infected
  cells

23
How does HIV cause disease

• HIV attacks the bodys defense system

Antibody production
Tcells that destroy virus infected cells
CD4 cells
HIV
24
Both CD4 cell Numbers and function affected !

• T-cell infection leading to cell death
• Large number of uninfected CD4 cells fuse with
  HIV infected cells. One infected cell accounts
  for deaths of many uninfected cells
• CD4 cells do not function as well

25
AIDS

• The result of infection with HIV is a inability
  of the body to defend itself against other
  invaders leading to opportunistic infections

26
Counseling tips

• Once diagnosed with AIDS, one should start on
  ARVs

27
SUMMARY

• Prolonged Asymptomatic HIV infection contributes
  to the epidemic
• HIV attacks the bodys defense system that would
  have otherwise eradicated the infection and
  helped in fighting other infections.
• Most important to prevent HIV infection because
  once infected, it is difficult to eradicate the
  virus

28
Thank you