HIV AND AIDS
PRESENTED BY DR. CHIHOMA MD
HIV – Human Immunodeficiency Virus –The virus that causes AIDS
AIDS –Acquired Immune Deficiency Syndrome
Immunity – The ability of the body to defend itself against infections and cancer cells
Immune system – a system of structures and processes within the body that protect against diseases by identifying and killing of pathogens and tumor cells
Antibody – proteins secreted by immune cells capable of binding and neutralizing harmful micro-organisms and some toxic substances.
Antigen– a substance that stimulates production of antibodies
Acquired immunity – immunity developed after exposure to antigens
CD4 +T Cells – Cells of the immune system which poses CD4 receptors used by HIV virus to bind to the cells. They are the leaders in acquired immunity and are the prime target of HIV.
Mutation – a change in the genetic material
DNA – a substance carrying organism’s genetic information except in some viruses
HIV / AIDS HISTORY
There is sufficient evidence that HIV originated in Africa before 1960
Between 1970 and 1980, African Doctors saw a rise of unusual (opportunistic) infections and wasting.
Prisoners and sex workers were among the victims and were diagnosed as having Mal absorption syndrome.
Thirty years ago (1981), the first cases of AIDS were described in New York and California.
The condition was first called Gay Related Immune Disease (GRID) because the first cases were gay men.
It was later described in injecting drug users (Heroin).
In 1982, the condition was reported among victims from Haiti and people with a bleeding disorder called Hemophilia.
The condition was then called 4H disease (4H for Homosexuals, Heroin users, Haitians and Hemophiliacs).
In 1982, the condition was reported in other groups worldwide and the name AIDS was created.
In 1983, the first case was diagnosed in Kagera region
In 1984, HIV was identified as the cause of AIDS (initially it was called HTLV-III OR LAV)
1986 The first ARV (AZT) was developed. Uganda started promoting behavioral change in response to AIDS.
1994 AZT was shown to reduce mother to child transmission of HIV
1996 – Combination treatment was shown to be highly effective against HIV
TYPES & ORIGIN OF HIV
There are two types of HIV i.e. HIV1 & HIV2
HIV1 is believed to have resulted from mutation of SIVcpz
SIVcpz infects the Apes (Chimpanzee) and causes a similar illness in chimps as AIDS in human beings.
HIV2 is believed to have resulted from mutation of SIVsm like SIVmac which infects the rhesus macaques
SIVsm infects monkeys especially the Sooty Mangabey but it is generally harmless in its natural host
HIV TYPES, GROUPS, and SUBTYPES
HIV1 and HIV2
Both HIV1&2 are transmitted by sexual contact, through blood & blood products, from mother to child
There are three groups of HIV – M (the Major group), N (the new group), And O (the outlier group)
There are 9 HIV subtypes (A,B,C,D,F,G,H,J & K)
In Tanzania, we have subtypes A, C and D
Subtype C is more virulent than most subtypes
SUSEPTIBLITY AND RESISTANCE TO HIV
Individuals with high concentrations of the carbohydrate based blood group known as pk are relatively resistant to HIV infection
Those with ought the pk molecule are 1000 times more sensitive to HIV infection
Individuals with ought the co receptor CCR5 are resistant to HIV infection (individuals who have inherited the CCR5 delta 32 mutation gene from both parents)
INTRODUCTION TO THE IMMUNE SYSTEM
The human immune system is a system of biological structures and processes within the body that protects against diseases by identifying and killing pathogens and tumor cells.
The immune system is composed of immune cells, specialized proteins, tissues and organs.
All cells of the immune system originate from the bone marrow.
Cells of the immune system
Lymphocytes – are the main group of the adaptive or acquired immune responses.
Other cells include Neutrophils, Monocytes, Basophils and Eosinophil in the blood, Macrophages, dendritic cells, Langham’s cells and microglia cells outside the blood vessels
DISORDERS OF THE IMMUNE SYSTEM
They can result in disease
Can be auto immune diseases whereby the immune system fails to recognise and spare one’s own body structures leading to self-destruction (hashimoto’s thyroiditis, rheumatoid arthritis, diabetes mellitus 1 and lupus erythromatosus)
Inflammatory and hyperactive immune responses
Can be immunodeficiency disease which occur when the immune system is less active
IMMUNODEFICIENCY DISEASES
Divided into two categories – Hereditary and Acquired immunodeficiency's
Hereditary immunodeficiency’s are genetically transmitted – there are more than 9 types
Acquired immunodeficiency’s are errors in the adaptive process.
CAUSES OF ACQUIRED IMMUNE DEFICIENCIES
Malnutrition is by far the commonest cause of acquired immune deficiency worldwide
Infections like HIV which destroys the immune cells
Drugs which suppress the bone marrow including drugs for cancer treatment, excessive consumption of septrin and chloramphenicol, some drugs which are used to treat AIDS etc.
CAUSES OF ACQUIRED IMMUNE DEFICIENCIES
Diseases which affect the bone marrow like cancer of the blood (leukaemia).
Radiations
HIV STRUCTURE AND LIFE CYCLE
The Human immunodeficiency virus is double strand RNA, roughly spherical particle.
The virus is enveloped.
On each viral envelop there are about 72 projections (gp120 & gp41) which are used for attachment and entry into target cells.
HIV STRUCTURE (continued)
Underneath the envelope is a layer of protein (gp17) which surrounds a third layer of protein (p24) (core).
Within the core are three essential enzymes for viral replication (reverse transcriptase, Integrase and protease) and a pair of HIV RNA strands.
HIV LIFE CYCLE
The infection starts with attachment using the viral projection on its envelope (gp120).
On the target cells, the gp120 binds to the CD4 molecule and one of its co receptor (CCR5 OR CXCR4).
binding allows the viral envelope and the cell membrane to fuse and brake releasing the viral material (nucleocapsid) into the CD4+ve cell.
The Reverse transcriptase converts viral RNA to viral DNA.
The Integrase then inserts just enough viral DNA into the host cell DNA.
Once viral DNA is inserted into the human cell, it remains so for life.
When the infected cell is activated, transcription of the viral DNA takes place producing viral messenger RNA.
The mRNA then migrates to the ribosome where it is translated to produce viral proteins and the essential enzymes.
Some of the proteins are resized by the enzyme Protease to produce the smaller viral core proteins.
Two viral RNA strands and replication enzymes then come together.
Core proteins assemble around them forming the nucleocapsid.
This immature virus leaves the host cell acquiring a new envelope of host and viral proteins.
The virus matures and becomes ready to infect other cells.
NATURAL HISTORY OF HIV INFECTION
Following the initial HIV infection a person remains without symptoms and signs for years depending on viral, environmental and host factors.
Viral factors include the type, group and sub type. HIV1 is more virulent than HIV2; group M being more virulent than groups O & N and subtype C being more virulent than most subtypes.
Host factors include individuals genetic factors like the carbohydrate based blood grouping molecules (pk), the concentration of the co - receptor (CCR5) and the production of ARCO antibodies which bind the viral GP120.
Nutritional factors
Environmental factors
A few HIV-1 infected individuals retain high levels of CD4+T cells without ARV therapy.
Most have detectable HIV in their blood and will more slowly progress towards AIDS.
These are classified as HIV CONTROLLERS or LONG TERM NON PROGRESSORS.
People who maintain CD4+T cell counts and also have low or undetectable viral load without ARV therapy are known as ELITE CONTROLLERS or ELITE SUPPRESSORS.
The natural history is divided into five stages:-
Primary HIV infection
Asymptomatic HIV infection
Early symptomatic HIV infection
Late symptomatic HIV infection
Advanced HIV infection
PRIMARY HIV INFECTION
May be asymptomatic
May be asymptomatic
Over 70% of new HIV infected individuals experience flu like symptoms including one or more of the following:- fever, skin rash and lymph node enlargement within the first two to three weeks.
There may be headache, muscle pain, joint pain, night sweats, diarrhoea, vomiting and nasal congestion.
At this stage, misdiagnosis is common because more common diseases like flu can cause these symptoms.
Opportunistic infections are not seen at this stage.
During this stage, the usual screening tests are negative.
ASYMPTOMATIC HIV INFECTION
Usually lasts ten years but may be between three to more than twenty years depending on viral, environmental and host factors
HIV infected individuals in this stage have no symptoms except persistent enlarged lymph nodes in some of them.
CD4 levels usually are above 500 cells/dL
EARLY SYMPTOMATIC HIV INFECTION
Skin rashes, recurrent fever, unexplained weight loss, fatigue, night sweats, fungal skin and nail infections, air way infections, diarrhoea, oral and vaginal fungal infections, recurrent herpes simplex are seen in this stage.
CD4 counts between 410 and 200 cells/dL
LATE SYMPTOMATIC HIV INFECTION
CD4 cells are between 200 – 50 cells/dl.
The risk of developing AIDS related opportunistic infections and cancers is very high.
Pneumocystis carini pneumonia (PCP), Toxoplasma encephalitis, Disseminated mycobacterium avium complex (MAC), Esophageal candidiasis, Lyphoma and Kaposi sarcoma occur in this stage.
ADVANCED HIV INFECTION
CD4 counts are below 50 cells/dl.
Usually the patient has multiple opportunistic infections and cancers.
Survival has improved following increased use of ART.
HIV PATHOPHYSIOLOGY
HIV causes progressive failure of the immune system allowing life threatening opportunistic infections and cancers to thrive.
HIV causes progressive failure of the immune system allowing life threatening opportunistic infections and cancers to thrive.
The four major roots of transmission are:-unsafe sex, transmission from an infected mother to her baby at birth, breast milk and contaminated needles.
At the entry point, HIV is trapped by specialised cells and is transferred to the regional lymph node for presentation to the CD4+T lymphocytes (about 72 hours).
HIV then enters the CD4+T lymphocyte and multiplies rapidly.
HIV causes a decrease in the number of CD4+T lymphocytes through three major mechanisms:-
(1) Busting of the infected CD4+T cell membranes following weakening as the virus buds off
(2) Increased rate of programmed cell death of HIV infected cells
(3) Activated CD8+T lymphocytes target and kills HIV infected CD4+T lymphocytes
When CD4+T lymphocytes numbers decrease bellow critical levels, the adaptive cell mediated immunity is lost
The body becomes more susceptible to opportunistic infections and cancers which are the major cause of death in AIDS.
HIV CARE AND TREATMENT
The primary aim is to prevent AIDS by maximally suppressing HIV for as long time as possible.
Ever since triple therapy was introduced in 1996, AIDS deaths have greatly reduced and survival increased from one to five years in 2005.
Survival is close to ten years with the first line combination (EFV/FTC/TENOFOVIR).
| Take considerable and significant care to your Health, at the end you will just be alone and it pains more when you have nobody to blame!!! |
