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group_3_presentation_3_-_hiv [2019/04/05 18:53] choetsoj [Conclusion] |
group_3_presentation_3_-_hiv [2019/04/05 21:21] (current) gilli1 [HIV Powerpoint] |
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| =======HIV Powerpoint======= | =======HIV Powerpoint======= | ||
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| ====== Introduction ====== | ====== Introduction ====== | ||
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| ===== History ===== | ===== History ===== | ||
| + | <box 20% round right | >{{ :hiv_virus.png?200|}} </box| Figure 1: Diagram of HIV virion. > | ||
| HIV is classified into two different groups, HIV-1 and HIV-2 <sup>[1]</sup>. HIV-1 is most commonly found around the world, while HIV-2 is less severe and targets a smaller population <sup>[1]</sup>. HIV-1 is found mostly in Africa, but it is present is almost every country (Sharp). HIV-1 is thought to be transmitted through a Simian immunodeficiency virus (SIV) found in chimpanzees <sup>[1]</sup>. While the exact origins of HIV are still unknown, one widely accepted theory is that it was passed to humans through hunting <sup>[2]</sup>. When hunters killed an animal with SIV, it was transmitted to humans through the blood of the chimpanzee <sup>[2]</sup>. SIV was then mutated to form HIV through multiple transmissions <sup>[2]</sup>. Patient zero is believed to have lived in Western Africa in southeast Cameroon <sup>[3]</sup>. HIV-1 is classified into three groups, M, N, and O, with group M being found all across the globe <sup>[1]</sup>. The oldest case of HIV is from 1959, a blood sample was found to have HIV-1 group M <sup>[2]</sup>. Recently, most countries have been seeing a decline in HIV rates <sup>[4]</sup>. Most people with HIV belong low or middle-income families, with lack of access to treatment or are unable to afford it <sup>[4]</sup>. There is now a World AIDS day on December 1st, created by WHO in 1988, to help raise awareness for HIV/AIDS <sup>[4]</sup>. | HIV is classified into two different groups, HIV-1 and HIV-2 <sup>[1]</sup>. HIV-1 is most commonly found around the world, while HIV-2 is less severe and targets a smaller population <sup>[1]</sup>. HIV-1 is found mostly in Africa, but it is present is almost every country (Sharp). HIV-1 is thought to be transmitted through a Simian immunodeficiency virus (SIV) found in chimpanzees <sup>[1]</sup>. While the exact origins of HIV are still unknown, one widely accepted theory is that it was passed to humans through hunting <sup>[2]</sup>. When hunters killed an animal with SIV, it was transmitted to humans through the blood of the chimpanzee <sup>[2]</sup>. SIV was then mutated to form HIV through multiple transmissions <sup>[2]</sup>. Patient zero is believed to have lived in Western Africa in southeast Cameroon <sup>[3]</sup>. HIV-1 is classified into three groups, M, N, and O, with group M being found all across the globe <sup>[1]</sup>. The oldest case of HIV is from 1959, a blood sample was found to have HIV-1 group M <sup>[2]</sup>. Recently, most countries have been seeing a decline in HIV rates <sup>[4]</sup>. Most people with HIV belong low or middle-income families, with lack of access to treatment or are unable to afford it <sup>[4]</sup>. There is now a World AIDS day on December 1st, created by WHO in 1988, to help raise awareness for HIV/AIDS <sup>[4]</sup>. | ||
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| The first case of AIDS was in the US in 1981, found in five gay men in Los Angeles <sup>[5]</sup>. In Canada, AIDS was first reported in 1982 <sup>[6]</sup>. Initially, HIV was associated with gay men and drug users, however, it is spread through unprotected hetereosexual intercourse in many countries. Through international travel and intercourse, HIV has spread all across the globe. HIV was first named “HIV” in 1986, and in 1987, FDA approved of the first antiretroviral therapy, zidovudine (AZT), for HIV <sup>[5]</sup>. In that same year, WHO confirmed mother-to-infant transmission for HIV and a blood test to detect for HIV was also introduced <sup>[5]</sup>. In 1994, the first oral test for HIV was introduced <sup>[5]</sup>. As of 2017, 59% of people with HIV are now on antiretroviral therapy <sup>[4]</sup>. Approximately 37 million people across the globe have HIV - of them, 9 million don’t know that they are infected <sup>[4]</sup>. HIV has killed around 35 million people globally, and 1.8 million people become newly infected by HIV in 2017 <sup>[4]</sup>. | The first case of AIDS was in the US in 1981, found in five gay men in Los Angeles <sup>[5]</sup>. In Canada, AIDS was first reported in 1982 <sup>[6]</sup>. Initially, HIV was associated with gay men and drug users, however, it is spread through unprotected hetereosexual intercourse in many countries. Through international travel and intercourse, HIV has spread all across the globe. HIV was first named “HIV” in 1986, and in 1987, FDA approved of the first antiretroviral therapy, zidovudine (AZT), for HIV <sup>[5]</sup>. In that same year, WHO confirmed mother-to-infant transmission for HIV and a blood test to detect for HIV was also introduced <sup>[5]</sup>. In 1994, the first oral test for HIV was introduced <sup>[5]</sup>. As of 2017, 59% of people with HIV are now on antiretroviral therapy <sup>[4]</sup>. Approximately 37 million people across the globe have HIV - of them, 9 million don’t know that they are infected <sup>[4]</sup>. HIV has killed around 35 million people globally, and 1.8 million people become newly infected by HIV in 2017 <sup>[4]</sup>. | ||
| ===== Causes ===== | ===== Causes ===== | ||
| + | <box 27% round right | >{{ :hiv_transmission_.png?300|}} </box| Table 1> | ||
| - | HIV is a sexually transmitted infection that is caused by unprotected sex <sup>[7]</sup> <sup>[8]</sup>. It can also be passed on to babies from their mothers before or during birth with rates ranging from 14-42% depending on various settings <sup>[7]</sup> <sup>[8]</sup> <sup>[9]</sup>. Moreover, it may also be transmitted during breastfeeding <sup>[7]</sup>. Although less common, HIV can also be transmitted by sharing needles either syringes or other injecting equipment <sup>[7]</sup>. Unlike other viruses which spread through the air, HIV is not easily passed from one person to the next <sup>[7]</sup>. Instead, for HIV transmission there needs to be fluid exchange between someone who has HIV and another person who does not have it <sup>[7]</sup>. | + | HIV is a sexually transmitted infection that is caused by unprotected sex <sup>[7]</sup> <sup>[8]</sup>. It can also be passed on to babies from their mothers before or during birth with rates ranging from 14-42% depending on various settings <sup>[7]</sup> <sup>[8]</sup> <sup>[9]</sup>. Moreover, it may also be transmitted during breastfeeding <sup>[7]</sup>. Although less common, HIV can also be transmitted by sharing needles either syringes or other injecting equipment <sup>[7]</sup>. Unlike other viruses which spread through the air, HIV is not easily passed from one person to the next <sup>[7]</sup>. Instead, for HIV transmission there needs to be a fluid exchange between someone who has HIV and another person who does not have it <sup>[7]</sup>. |
| There are a few targeted ways that the virus can enter the bloodstream. Initially, the virus can enter if it is injected into the bloodstream with needles or other equipment that has been used by other people who have been infected by HIV <sup>[7]</sup>. Additionally, it can enter through the lining on or inside the anus, vagina, and/or genitals <sup>[7]</sup>. It is also possible for the virus to enter through the lining of the mouth and eyes and from cuts or sores in the skin <sup>[7]</sup>. | There are a few targeted ways that the virus can enter the bloodstream. Initially, the virus can enter if it is injected into the bloodstream with needles or other equipment that has been used by other people who have been infected by HIV <sup>[7]</sup>. Additionally, it can enter through the lining on or inside the anus, vagina, and/or genitals <sup>[7]</sup>. It is also possible for the virus to enter through the lining of the mouth and eyes and from cuts or sores in the skin <sup>[7]</sup>. | ||
| - | |||
| ===== Pathophysiology ===== | ===== Pathophysiology ===== | ||
| - | |||
| - | <box 18% round right | > </box| Figure 3:> | ||
| HIV has a cylindrical center that is surrounded by a lipid bilayer envelope. In this bilayer envelope, there are 2 primary proteins, which are gp120 and gp41 <sup>[10]</sup>. These are used to help with the recognition of the CD4+ T helper cells allowing the virus to attach and invade <sup>[10]</sup>. These CD4+ cells are used in the body's natural immune response to help activate the active B cells, killer cells, and macrophages. When the HIV virus binds to these cells it will have copies of genomic material, RNA, multiple proteins and enzymes all of which are crucial for invasion <sup>[10]</sup>. In order to alter the genetic makeup of the immune cell the HIV virus will undergo reverse transcription <sup>[10]</sup>. Through this process, it will code for 3 principal genes, which are gag, pol, and env <sup>[11]</sup>. The gag gene will help to encode the core proteins in the cell <sup>[11]</sup>. The pol gene is what will code the reverse transcriptase, which is the protein that is necessary when undergoing this process <sup>[11]</sup>. Finally, the env gene is used for the structural components of HIV <sup>[11]</sup>. This can include glycoproteins, which will help to provide support for the cells. | HIV has a cylindrical center that is surrounded by a lipid bilayer envelope. In this bilayer envelope, there are 2 primary proteins, which are gp120 and gp41 <sup>[10]</sup>. These are used to help with the recognition of the CD4+ T helper cells allowing the virus to attach and invade <sup>[10]</sup>. These CD4+ cells are used in the body's natural immune response to help activate the active B cells, killer cells, and macrophages. When the HIV virus binds to these cells it will have copies of genomic material, RNA, multiple proteins and enzymes all of which are crucial for invasion <sup>[10]</sup>. In order to alter the genetic makeup of the immune cell the HIV virus will undergo reverse transcription <sup>[10]</sup>. Through this process, it will code for 3 principal genes, which are gag, pol, and env <sup>[11]</sup>. The gag gene will help to encode the core proteins in the cell <sup>[11]</sup>. The pol gene is what will code the reverse transcriptase, which is the protein that is necessary when undergoing this process <sup>[11]</sup>. Finally, the env gene is used for the structural components of HIV <sup>[11]</sup>. This can include glycoproteins, which will help to provide support for the cells. | ||
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| ===== Symptoms ===== | ===== Symptoms ===== | ||
| - | <box 20% round right | > </box| Figure 5: Common Motor Symptoms seen in PD.> | + | <box 20% round right | > {{ :hiv_symptoms.png?200 |}} </box| Figure 2: Annotated illustration showing common symptoms of HIV.> |
| The symptoms of HIV vary, depending on the phase of infection. | The symptoms of HIV vary, depending on the phase of infection. | ||
| === Primary infection (Acute HIV) === | === Primary infection (Acute HIV) === | ||
| - | Most people infected by HIV develop a flu-like symptoms within a month or two after the virus enters the body <sup>[15]</sup>. This is known as primary or acute HIV infection, which can last for a few weeks. Possible signs and symptoms include: | + | Most people infected by HIV develop flu-like symptoms within a month or two after the virus enters the body <sup>[15]</sup>. This is known as primary or acute HIV infection, which can last for a few weeks. Possible signs and symptoms include: |
| - | Fever | + | * Fever |
| - | Headache | + | * Headache |
| - | Nausea and Vomiting | + | * Nausea and Vomiting |
| - | Aching muscles | + | * Aching muscles |
| - | Sore throat and painful mouth sores | + | * Sore throat and painful mouth sores |
| - | Swollen lymph glands, mainly on the neck | + | * Swollen lymph glands, mainly on the neck |
| These symptoms can be so mild that you might not even notice them. However, the amount of virus in your bloodstream is quite high at this time <sup>[15]</sup>. As a result, the infection spreads more easily during primary infection than during the next stage. | These symptoms can be so mild that you might not even notice them. However, the amount of virus in your bloodstream is quite high at this time <sup>[15]</sup>. As a result, the infection spreads more easily during primary infection than during the next stage. | ||
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| As the virus continues to multiply and destroy immune cells, the cells in your body that help fight off germs may develop mild infections or chronic signs and symptoms such as: | As the virus continues to multiply and destroy immune cells, the cells in your body that help fight off germs may develop mild infections or chronic signs and symptoms such as: | ||
| - | Fever | + | * Fever |
| - | Fatigue | + | * Fatigue |
| - | Swollen lymph nodes | + | * Swollen lymph nodes |
| - | Diarrhea | + | * Diarrhea |
| - | Weight loss | + | * Weight loss |
| - | Oral yeast infection | + | * Oral yeast infection |
| - | Shingles | + | * Shingles |
| ===== Diagnosis ===== | ===== Diagnosis ===== | ||
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| === Enzyme immunoassay (EIA) === | === Enzyme immunoassay (EIA) === | ||
| - | Enzyme immunoassay is a common immunological technique that has been adapted for the detection of HIV antibodies. EIAs have a high sensitivity and specificity and are able to detect all subtypes of HIV <sup>[17]</sup>. EIAs screen large numbers of specimens (about 90 or more at a time). An EIA procedure takes around two hours, hence some large-scale labs are able to report the EIA results the same day. EIAs require sophisticated equipment, and are technically demanding; automatic pipettes, incubators, washers, readers and a constant electricity supply must be available. The validity of the test results depends on the skills of technicians, who prepare the necessary reagents and operate the equipment <sup>[17]</sup>. | + | Enzyme immunoassay is a common immunological technique that has been adapted for the detection of HIV antibodies. EIAs have a high sensitivity and specificity and are able to detect all subtypes of HIV <sup>[17]</sup>. EIAs screen large numbers of specimens (about 90 or more at a time). An EIA procedure takes around two hours, hence some large-scale labs are able to report the EIA results the same day. EIAs require sophisticated equipment, and are technically demanding; automatic pipettes, incubators, washers, readers and constant electricity supply must be available. The validity of the test results depends on the skills of technicians, who prepare the necessary reagents and operate the equipment <sup>[17]</sup>. |
| + | <box 30% round right | > {{ :western_blot.png?300|}} </box| Figure 3: Image displaying the various steps in a Western Blotting (WB) test.> | ||
| === Rapid Test Devices === | === Rapid Test Devices === | ||
| - | Rapid antibody tests are qualitative immunoassays that should be used in combination with the clinical status, history, and risk factors of the person being tested. Rapid test devices with diagnostic performance comparable to that of traditional EIA methods are currently commercially available <sup>[17]</sup>. These assays are helpful to use in resource-limited settings since they can be performed in clinic or community settings and little equipment is required. Most rapid tests are presented as a kit incorporating the reagents, and do not usually require additional equipment <sup>[17]</sup>. Rapid HIV assays are quick and easy to perform, making them more cost-effective than EIAs. As the procedures are simpler and involve a limited number of steps, there is a lesser chance of error and they can be carried out by health-care workers who have received appropriate training <sup>[17]</sup>. Test results become available within 10–30 minutes. | + | Rapid antibody tests are qualitative immunoassays that should be used in combination with the clinical status, history, and risk factors of the person being tested. Rapid test devices with diagnostic performance comparable to that of traditional EIA methods are currently commercially available <sup>[17]</sup>. These assays are helpful to use in resource-limited settings since they can be performed in clinic or community settings and little equipment is required. Most rapid tests are presented as a kit incorporating the reagents and do not usually require additional equipment <sup>[17]</sup>. Rapid HIV assays are quick and easy to perform, making them more cost-effective than EIAs. As the procedures are simpler and involve a limited number of steps, there is a lesser chance of error and they can be carried out by health-care workers who have received appropriate training <sup>[17]</sup>. Test results become available within 10–30 minutes. |
| === Western Blotting === | === Western Blotting === | ||
| - | The WB assay consists of a multilayer process similar to an EIA <sup>[17]</sup>. HIV antigens are laid out on a strip from the highest in molecular weight to the lowest. When a specimen is incubated with the strip, any existing HIV antibodies bind to these HIV antigens <sup>[17]</sup>. An antibody–enzyme complex is formed with the addition of the enzyme. Then a chemical is added that changes colour when it comes into contact with the protein–antibody–enzyme layers <sup>[17]</sup>. | + | The WB assay consists of a multilayer process similar to an EIA <sup>[17]</sup>. HIV antigens are laid out on a strip from the highest in molecular weight to the lowest. When a specimen is incubated with the strip, any existing HIV antibodies bind to these HIV antigens <sup>[17]</sup>. An antibody-enzyme complex is formed with the addition of the enzyme. Then a chemical is added that changes colour when it comes into contact with the protein–antibody–enzyme layers <sup>[17]</sup>. |
| ===== Drugs and Medication ===== | ===== Drugs and Medication ===== | ||
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| ===== Future Therapeutics ===== | ===== Future Therapeutics ===== | ||
| - | With the current therapies there are a few new therapeutics that are also being explored. There is the “shock-and-kill” strategy, gene therapy which is also being researched, and broadly neutralizing antibodies which have been analyzed. | + | With the current therapies, there are a few new therapeutics that are also being explored. There is the “shock-and-kill” strategy, gene therapy which is also being researched, and broadly neutralizing antibodies which have been analyzed. |
| + | |||
| + | |||
| + | <box 27% round right | > {{ :shock_and_kill.png?300|}} </box| Figure 4: Image showing the mechanisms of the shock and kill strategy on HIV infected cells > | ||
| ==== Shock-and-Kill Approach ==== | ==== Shock-and-Kill Approach ==== | ||
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| ==== Gene therapy ==== | ==== Gene therapy ==== | ||
| - | Another therapy is gene therapy through three different strategies <sup>[31]</sup>. First, it targets the proviral genome directly through a gene editing technology which could include clustered regularly interspaced short palindromic repeats (CRISPR) or through transcriptional silencing <sup>[31]</sup><sup>[32]</sup>. The second step includes targeting future HIV infections by blocking HIV from entering by releasing certain proteins or build an HIV resistance by modifying HIV receptors through gene editing <sup>[31]</sup><sup>[33]</sup>. Lastly, this approach uses immunotherapy-based approaches that are currently being used in clinical trials for cancer. The aim of immunotherapy-based approached is to genetically modify T cells or natural killer cells to identify and bind to target cell types and eliminate them <sup>[31]</sup>. | + | Another therapy is gene therapy through three different strategies <sup>[31]</sup>. First, it targets the proviral genome directly through a gene editing technology which could include clustered regularly interspaced short palindromic repeats (CRISPR) or through transcriptional silencing <sup>[31-32]</sup> . The second step includes targeting future HIV infections by blocking HIV from entering by releasing certain proteins or build an HIV resistance by modifying HIV receptors through gene editing <sup>[31]</sup><sup>[33]</sup>. Lastly, this approach uses immunotherapy-based approaches that are currently being used in clinical trials for cancer. The aim of immunotherapy-based approached is to genetically modify T cells or natural killer cells to identify and bind to target cell types and eliminate them <sup>[31]</sup>. |
| ==== Broadly Neutralizing Antibodies ==== | ==== Broadly Neutralizing Antibodies ==== | ||
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| [33] Burke BP, Levin BR, Zhang J, Sahakyan A, Boyer J, Carroll MV, Colón JC, Keech N, Rezek V, Bristol G, Eggers E. Engineering cellular resistance to HIV-1 infection in vivo using a dual therapeutic lentiviral vector. Molecular Therapy-Nucleic Acids. 2015 Jan 1;4:e236. | [33] Burke BP, Levin BR, Zhang J, Sahakyan A, Boyer J, Carroll MV, Colón JC, Keech N, Rezek V, Bristol G, Eggers E. Engineering cellular resistance to HIV-1 infection in vivo using a dual therapeutic lentiviral vector. Molecular Therapy-Nucleic Acids. 2015 Jan 1;4:e236. | ||
| - | [34] Gama L, Koup RA. New-generation high-potency and designer antibodies: role in HIV-1 treatment. Annual review of medicine. [20]2018 Jan 29;69:409-19. | + | [34] Gama L, Koup RA. New-generation high-potency and designer antibodies: role in HIV-1 treatment. Annual review of medicine. 2018 Jan 29;69:409-19. |
