Inhibition Of Hivs Entry
The entry of HIVs is currently understood to be essentially a three-step process consisting of attachment, chemokine co-receptor interaction, and fusion. Therefore, specific areas of interest to inhibit HIVs entry include blocking gp120 binding to CD4 cell receptors , blocking the binding sites of co-receptors such as CCR5 and CXCR4 , and disrupting the fusion process .
The fusion inhibitor, enfuvirtide , a 36-amino acid peptide being developed jointly by Trimeris and Roche, is in the most advanced stage of clinical development. HIV fusion with CD4 cells is a complex process, and not very well understood, and involves a conformational change in the HIV envelope gp120/gp41, leading to an interaction between gp41 that lead to intimate proximity between the HIV envelope and the cell membrane, allowing fusion to occur. Enfuvirtide is active against both CCR-5- and CXCR4-using viruses and are synergistic with CCR5 and CXCR4 antagonists.
How Does Chronic Hiv Affect The Body
The chronic HIV stage is known as the latent or asymptomatic stage. During this stage, a person usually wont have as many symptoms as they did during the acute phase. This is because the virus doesnt multiply as quickly.
However, a person can still transmit HIV if the virus is left untreated and they continue to have a detectable viral load. Without treatment, the chronic HIV stage can last for many years before advancing to AIDS.
Advances in antiretroviral treatments have significantly improved the outlook for people living with HIV. With proper treatment, many people who are HIV-positive are able to achieve viral suppression and live long, healthy lives. Learn more about HIV and life expectancy.
A normal CD4 count ranges from approximately 500 to 1,600 cells per cubic millimeter of blood in healthy adults, according to HIV.gov.
A person receives an AIDS diagnosis when they have a CD4 count of fewer than 200 cells/mm3.
The survival rate for people with AIDS varies depending on treatment and other factors.
How Does Acute Hiv Affect The Body
Once a person contracts HIV, the acute infection takes place immediately.
Symptoms of the acute infection may take place days to weeks after the virus has been contracted. During this time, the virus is multiplying rapidly in the body, unchecked.
This initial HIV stage can result in flu-like symptoms. Examples of these symptoms include:
- myalgias, or muscle pain
However, not all people with HIV experience initial flu-like symptoms.
The flu symptoms are due to the increase of copies of HIV and widespread infection in the body. During this time, the amount of CD4 cells starts to fall very quickly. The immune system then kicks in, causing CD4 levels to rise once again. However, the CD4 levels may not return to their pre-HIV height.
In addition to potentially causing symptoms, the acute stage is when people with HIV have the greatest chance of transmitting the virus to others. This is because HIV levels are very high at this time. The acute stage typically lasts between several weeks and months.
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Macrophages And Myeloid Cells
Found primarily in tissues, macrophages are mononuclear leukocytes that are key components of innate immunity. For decades, the origin of tissue resident macrophages was explained by the concept of the mononuclear-phagocyte system: monocytes were thought to continually replenish TRM that died in tissues . Consistent with this early concept, the death of HIV-1 infected macrophages was thought to be responsible for the second phase of HIV-1 viral kinetic decline during ART. However, recent findings based on murine models suggest that the principal origin of TRM in steady state is from embryonic haematopoietic precursors, while monocytes only contribute in the setting of inflammation and injury . Similarly, detection of TRM even in individuals with monocytopenia suggests monocyte-independent maintenance, a long half-life of embryonically derived macrophages, or likely a combination of both . Studies in patients who received lung transplantation have also shown long-term persistence of donor alveolar macrophages . In parallel, the rapid second phase decline of HIV-1 was found not to be attributable to macrophages . Taken together, these findings have led to a marked revision in our understanding of the maintenance and longevity of TRM.
How Do People Get Hiv
HIV spreads when infected blood or body fluids enter the body. This can happen:
HIV also can pass from mother to child during pregnancy, childbirth, or breastfeeding.
HIV is NOT spread through:
- pee, poop, spit, throw-up, or sweat
- coughing or sneezing
- sharing eating utensils or drinking glasses
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Hiv Effects On The Digestive System
More than half of people who have AIDS report digestive symptoms as the virus or an opportunistic infection targets the walls of their intestines. Diarrhea is the most common one. Over time, the virus can change how your digestive tract works and even how it looks.
Some HIV medications can damage your liver. Many people with HIV also have a form of inflammation called hepatitis.
Limit how much alcohol you drink, and don’t use recreational drugs. Having diabetes, high cholesterol, or triglycerides and being overweight can lead to fatty liver disease, so keep an eye on the carbs, fats, and calories you eat each day.
Talk to your doctor about getting the hepatitis A and hepatitis B vaccines. Thereâs no vaccine against hepatitis C, but you should get tested for it.
Get regular blood tests to catch any liver problems early.
Your mouth might be one of the first places where you notice signs of HIV. Things like dry mouth, fungal infections, gum disease, cold sores, and canker sores can make chewing or swallowing painful. If they go on too long, you might not be able to take your HIV medication or get the nutrients you need.
Good dental habits can help prevent these issues, so brush and floss regularly. See your dentist for checkups, and tell them if youâre having problems. Most mouth conditions tied to HIV are treatable.
What Are The Factors That Affect Disease Progression
The most important factor affecting HIV progression is the ability to achieve viral suppression. Taking antiretroviral therapy regularly helps many people slow the progression of HIV and reach viral suppression.
However, a variety of factors affect HIV progression, and some people progress through the phases of HIV more quickly than others.
Factors that affect HIV progression can include:
- Ability to achieve viral suppression. Whether someone can take their antiretroviral medications and achieve viral suppression is the most important factor by far.
- Age when symptoms start. Being older can result in faster progression of HIV.
- Health before treatment. If a person had other diseases, such as tuberculosis, hepatitis C, or other sexually transmitted diseases , it can affect their overall health.
- Timing of diagnosis. Another important factor is how soon a person was diagnosed after they contracted HIV. The longer between their diagnosis and treatment, the more time the disease has to progress unchecked.
- Lifestyle. Practicing an unhealthy lifestyle, such as having a poor diet and experiencing severe stress, can cause HIV to progress more quickly.
- Genetic history. Some people seem to progress more quickly through their disease given their genetic makeup.
Some factors can delay or slow the progression of HIV. These include:
Living a healthy lifestyle and seeing a healthcare provider regularly can make a big difference in a persons overall health.
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Hivs Affect On Receptor Usage
To speculate as to why HIVs have evolved plasticity in their interactions with co-receptors is important. The ability to use multiple functionally redundant contacts with co-receptors could conceivably facilitate immunological escape. Thus, in the face of a neutralising antibody response , the selection of variants with altered envelope sequences would be permitted without compromising the ability of the virus to use a given co-receptor. Furthermore, changes in envelope sequence, that enable the virus to use additional co-receptors while retaining the ability to interact with CCR-5, could be tolerated. It appears that dual-tropic strains that use both CCR-5 and CXCR-4 are less tolerant of perturbations in CCR-5 sequence than are M-tropic strains,, suggesting that acquisition of the ability to utilise CXCR-4 might involve the sacrifice of a degree of functional redundancy and/or affinity in the envelope/CCR-5 interaction.
Usual And Unusual Suspects
Viral latency is defined as a reversible nonproductive state of infection in individual cells . Reservoirs are cells that harbor replicative forms of HIV-1 following long periods of ART-suppressed viremia . Resting memory CD4+ T cell reservoirs have been estimated to have a half-life of 44 months, meaning that their clearance during ART may take as long as 73 years . Subsequently, distinct populations of CD4+ T cells have also been recognized to contribute to the pool of latently infected cells , although those are outside the scope of the present review. The half-life of resting memory CD4+ T cell reservoirs corresponds to the long-phase decay of residual plasma viremia in persons taking long-term ART . The phases of plasma HIV-1 RNA decline on ART have been attributed to infection of different cell types that are infected by the virus, and much has been inferred about the identities of those cells without clear evidence . Here, we enumerate several candidate cell types that could potentially serve as HIV-1 reservoirs .
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Effects On The Immune System
HIV primarily affects the body by targeting and damaging cells in the immune system. The immune system protects the body against viruses, bacteria, and fungi.
After attaching itself to a type of white blood cell called a CD4 T cell, the virus merges with it. These T cells are an important part of the immune system.
Once inside the CD4 T cell, the virus multiplies. It damages or destroys the cell, then moves on and targets other cells.
A persons CD4 T-cell count is an indication of the health of their immune system.
A healthy CD4 T-cell count is 5001,600 cells/mm3 of blood. If a person does not receive treatment for HIV, their CD4 T-cell count drops over time.
When it drops below 200 cells/mm3, the persons immune system is significantly impaired, making them more susceptible to opportunistic infections.
Hiv Effects On The Nervous System
About half of people with AIDS have nerve problems related to the virus. Infection or inflammation can damage your spinal cord or brain and keep your nerve cells from working the way they should. Some medications can also affect your nervous system.
Inflammation in your brain and spinal cord can lead to confusion and other thinking problems as well as weakness, headaches, seizures, and balance problems.
When AIDS is far along, you might get dementia and have problems remembering things.
Having HIV can also affect your mental health. Many people living with it have depression or anxiety. Mental health professionals and support groups can help you work through your concerns and manage your life with HIV.
The opportunistic infection cytomegalovirus can attack your nerves, making it hard for you to control your arms and legs or your bladder.
Itâs common for tiny holes to form in spinal fibers when people with AIDS donât get treatment. This is called vacuolar myelopathy and causes trouble walking.
HIV or the drugs that treat it can also damage nerves all over your body, causing neuropathy. You might have pain, numbness, weakness, burning, stiffness, or tingling.
Antiretroviral therapy to treat HIV can lower your risk of getting these conditions or complications. If a medication is causing the problems, your doctor might switch you to a different one.
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Where In The Body Does Hiv Infection Occur
HIV targets the lymphocyte type of white blood cell. There are three components to the blood: red blood cells, white blood cells and plasma. Although blood appears red when it comes out of the body, if one were to put it in a centrifuge, it would separate out. A wide clear band of plasma would rise to the top and the red blood cells would sink to the bottom. In the middle would be a thin layer of white blood cells.
Dynamics Of Hiv Infection
After initial entry of HIV and establishment of infection, replication may at first occur within inflammatory cells at the site of infection or within peripheral blood mononuclear cells, but then the major site of replication quickly shifts to lymphoid tissues of the body, including those in lymph nodes, spleen, liver, and bone marrow. Besides lymph nodes, the gut associated lymphoid tissue provides a substantial reservoir for HIV.
Macrophages and Langerhans cells in epithelia such as in the genital tract are important both as reservoirs and vectors for the spread of HIV in the body. Langerhans cells act as antigen presenting cells for CD4 lymphocytes. Both macrophages and Langerhans cells can be HIV-infected but are not destroyed themselves. HIV can then be carried elsewhere in the body. Within lymph nodes, HIV virions are trapped in the processes of follicular dendritic cells , where they may infect CD4 lymphocytes that are percolating through the node. The FDC’s themselves become infected, but are not destroyed.
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What Is A Cd4 Count
A CD4 count is a test that measures the number of CD4 cells in your blood. CD4 cells, also known as T cells, are white blood cells that fight infection and play an important role in your immune system. A CD4 count is used to check the health of the immune system in people infected with HIV .
HIV attacks and destroys CD4 cells. If too many CD4 cells are lost, your immune system will have trouble fighting off infections. A CD4 count can help your health care provider find out if you are at risk for serious complications from HIV. The test can also check to see how well HIV medicines are working.
Other names: CD4 lymphocyte count, CD4+ count, T4 count, T-helper cell count, CD4 percent
How Are Hiv And Aids Treated
Medicines can help people with HIV stay healthy. They can also prevent HIV from progressing to AIDS.
Health care providers prescribe a combination of different medicines for people with HIV and AIDS. They must be taken exactly as prescribed or they won’t work. These medicines:
- help keep the number of CD4 cells high
- reduce the viral load of HIV
Regular blood tests will check the number of CD4 cells in the body and the viral load.
If an HIV-positive person’s CD4 count gets low, doctors prescribe daily antibiotics. This prevents pneumocystis pneumonia, which happens in people with weakened immune systems.
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Hiv Effects On The Circulatory System
Several things make your chances of heart-related problems go up. Because HIV affects your immune system, your body will be inflamed as it tries to fight the infection, like itâs on a constant simmer. This kind of inflammation has been linked to heart disease.
Some drugs you take for HIV can also make heart disease more likely. They can cause insulin resistance, which makes you more likely to get diabetes, and problems breaking down fats. Diabetes, in turn, raises your risk of heart disease. You might need medicines to control your blood sugar and cholesterol.
If you smoke, quit. Eat a variety of vegetables and fruits, plenty of whole grains, and foods with omega-3 fatty acids. Choose lean cuts of meat and low-fat dairy products. Exercise, like taking a brisk walk, for 20 to 30 minutes most days of the week.
If you’re carrying extra weight, losing as little as 5 or 10 pounds could make a big difference.
The Human Immunodeficiency Viruses
The HIVs are members of the lentivirus subgroup of the Retroviridae family. They are RNA viruses that posses the enzyme reverse transcriptase . This enzyme allows the virus to reverse-transcribe its own RNA, and the resultant complementary DNA is incorporated into the cellular DNA of the host. Two main types of HIV exist: HIV-1 and HIV-2, which differ in genomic structure and antigenicity as well as in their latent period as pathogenicity. HIV-1 was identified, as the causative agent of AIDS, by three different groups in the early eighties. These were Montagniers at the Pasteur Institute in Paris , Gallos at the National Institute of Health USA, and Levys at the University of California San Francisco , USA. The HIVs were initially called LAV , HTLV-III-human T lymphotropic virus and ARV .,, In 1986 a second virus was identified, and the original was renamed HIV-1 to distinguish them. The diameter of the HIV virion is approximately 100 nm and electron microscopy studies have revealed a characteristic cylindrical core in HIV particles surrounded by an outer envelope .
Electron micrograph of HIV-1 and HIV-2 .
HIV-1 virions are shown budding . HIV-2 virions are shown in . Magnification is 100,000 x. Scale bar =100nm.
This electron microscopy was kindly performed by Dr. Robert Dourmashkin.
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What Does Hiv Do To The Immune System
The term HIV is often synonymously used with AIDS. However, it is important to understand the distinctions between these medical terms. Sadly, many people are quite unfamiliar with the symptoms of HIV, how HIV is transmitted, and the progression of HIV to AIDS. This lack of knowledge puts them at a high risk of HIV transmission.
First, lets explain what HIV is.
HIV stands for human immunodeficiency virus. HIV is transmitted from one person to another through bodily fluids such as semen, blood, or vaginal discharge. It is most commonly transmitted through unprotected sex, as well as with intravenous needles, blood contamination, or a pregnant mother living with HIV can pass the virus to a baby.
People can go many years without knowing that they have HIV. In fact, it is estimated that about 1 in 7 people are HIV positive but are unaware as they have never been tested. However, over ten years or so, their immune system will become extremely compromised until they develop AIDS unless they take HIV treatment drugs.
So, how does this happen and why does HIV attack the immune system? Lets dive in.