HIV E-book Flashcards
Initial risk groups:
o Men who have sex with men (MSM)
o Injecting drug users
o Recipients of blood products
What are HIV and AIDS?
The Human Immunodeficiency Virus (HIV) is a lentivirus (a member of the retroviridae family). As such it is an RNA virus which cannot insert itself into host DNA until it recodes itself into double-stranded DNA. To replicate, retroviruses must convert their genetic material into host genetic material through the process of reverse transcription which is accomplished by the viral enzyme reverse transcriptase.
Acquired Immune Deficiency Syndrome (AIDS) was first clinically described in late 1980 and early 1981. Initially it was observed as cases of Pneumocystis carinii - now jiroveci - (PCP) infections in homosexual men and injecting drug users.
There are two types of HIV infection
HIV-1 and HIV-2
- Both types can be transmitted by sexual contact, through blood and from mother to child. Both appear to cause clinically indistinguishable AIDS.
Which strain of HIV is responsible for the global HIV epidemic
HIV-1 Group M
HIV-2
The HIV-2 virus has five phylogenetically distinct forms which are largely concentrated in West Africa but now seem to be spreading to India. These subtypes appear to be less harmful and less transmissible in humans compared to HIV-1.
HIV-1
The HIV-1 virus is divided into four groups: M, N, O and P. These represent separate introductions from Simian Immunodeficiency Virus (SIV) into humans. Group M has nine genetic subtypes (called clades) with varying global distributions. Group M, subtype C is the most prevalent and accounts for > 55% of all HIV-1 infections.
The human body’s main defence against HIV is
skin
HIV particles are surrounded by
HIV particles are surrounded by a fatty membrane, through which protrude 72 protein spikes comprising gp41 and gp120. Within the viral core are two identical strands of RNA along with the enzymes necessary for the cell to replicate: reverse transcriptase, integrase and protease.
In order to replicate once in the body, HIV must
In order to replicate once in the body, HIV must enter a cell. The gp120 protein binds tightly to CD4 receptors on host cells. CD4 is found on the surface of T-helper cells, regulatory Tcells, monocytes, macrophages and dendritic cells. Then there is a conformational change in the gp120 which allows it to bind to a chemokine co-receptor (CCR5 on macrophages or CXCR4 on T helper cells). Drugs which act at this point in the infection process are known as entry inhibitors. Once the secondary binding occurs, the HIV gp41 interacts with the host cell fusing the HIV particle to the host cell. Once fused, the HIV RNA and the three enzymes can enter the host cell. Fusion inhibitors work at this point of the process.
Once into the cell, the
Once into the cell, the viral reverse transcriptase converts the viral RNA into viral DNA in the cytoplasm of the host cell. Nucleoside and non-nucleoside reverse transcriptase inhibitors target this conversion process. The viral DNA then moves into the host cell nucleus and becomes spliced into the host cell DNA forming a provirus using the viral integrase to facilitate the process. Integrase inhibitors target this integration of HIV DNA with host cell
DNA. Messenger RNA is then produced and the host cell’s mRNA template is utilized to produce viral proteins and enzymes. Once this translation has occurred, precursor proteins from the immature viral core are cut into smaller functional proteins by the viral protease and a viral particle is formed. This viral particle then buds off from the cell resulting in infectious virons being released into the blood stream. Protease inhibitors interfere with this final process in the HIV replication cycle
Antiretroviral drugs
- Fusion Inhibitors
- Nucleoside and nonnucleoside reverse transcriptase inhibitors (NNRTI’s & NRTI)
- Integrase inhibitors
- Protease inhibitors
HIV testing
Third generation tests
Fourth generation tests
Rapid HIV tests
Polymerase Chain Reaction (PCR) Tests.
Third generation tests
Third generation tests are an ELISA antibody test. It is inexpensive, accurate and very sensitive. If antibodies to HIV are detected then the patient is infected with HIV. The disadvantage with third generation tests is that it they only become accurate after 12 weeks, as it takes a person 6-12 weeks to raise antibodies against HIV. Third generation tests conducted before 12 weeks may result in a false negative response.
Fourth generation tests
Fourth generation tests are ELISA tests which detect antibodies and p24 antigens. As viral load increases dramatically during the first few weeks of infection, these tests will detect HIV in the great majority of individuals one month post exposure, and possibly as soon as 11
days post exposure. As a result the British association for Sexual Health and HIV (BASHH) recommends that anyone presenting for a HIV test within four weeks of exposure should be offered a fourth generation test with a follow up four weeks post exposure. This is because
a person is highly infectious within the first weeks following infection.
Self-testing kits for HIV are now available in the US, UK and France. They can be ordered online from www.test.hiv these rely on fourth generation technology, results are given to patients confidentially within a two-week timeframe due to having to post the tests to a
central laboratory.
Rapid HIV tests
Rapid HIV tests include the OraQuick HIV-1 and HIV-2 rapid test kit which works on the same principle as ELISA tests. They produce results within 20 minutes. The test uses either a blood sample or oral fluids, is easy to use, has no need for laboratory facilities and has no need for highly trained staff. All positive results from a rapid test must be followed up with a confirmatory standard ELISA test.
The Polymerase Chain Reaction (PCR)
The Polymerase Chain Reaction (PCR) test detects HIV genetic material rather than the viral antibodies. It can identify HIV in blood samples within 2-3 weeks of infection. Babies born to HIV positive mothers are usually tested with the PCR test because they retain maternal
HIV antibodies for several months after birth which would give a false positive on an ELISA test. PCR tests are not used for routine HIV detection in adults as the tests are expensive, more complicated to administer and more difficult to interpret than a standard ELISA test.
HIV disease progression
HIV attacks the immune system by destroying CD4 positive T cells (CD4 cells). These Thelper cells are involved in the co-ordination of the immune response and their destruction means that people infected with HIV are vulnerable to opportunistic infections (OIs) and other complications
There are two parameters used to monitor the progression of HIV virus:
the CD4 cell count and the viral load. The CD4 count is used as a marker for the health of an individual’s immune system.
In HIV infection a second marker, the plasma viral load (a measure of plasma HIV RNA), is also used. If the plasma viral load decreases, the CD4 count will rise.
In a healthy adult, the CD4 count is somewhere between
800 and 1500 cells/µl.
There are three clinical presentations of HIV
primary HIV infection, chronic HIV infection and AIDS.
Symptoms of primary HIV infection
Rash Fever Weight loss Persistent lymphadenopathy Diarrhoea for longer than four days Malaise Headaches
Non-specific symptoms of chronic HIV
Rapid weight loss Recurring fever Profuse night sweats Prolonged swelling of the lymph glands Immunosuppression related conditions
A diagnosis of AIDS is made when
A diagnosis of AIDS is made when a HIV infected person presents with one or more AIDS defining illnesses and a CD4 count below 200 cells/µl. AIDS defining illnesses include opportunistic infections and malignancies. These occur due to the destruction the immune system, and prevention of normal immune responses by the HIV virus.
AIDS defining illnesses
Cryptococcal meningitis Cytomegalovirus disease Mycobaterium avium complex (MAC) Pneumocystis pneumonia (PCP) Progressive multifocal leucoencephalopathy (PML) Toxoplasmosis encephalitis Tuberculosis Cervical cancer Kaposi’s sarcoma Non-Hodgkin’s lymphoma Primary cerebral lymphoma
