Tuesday, January 31, 2023

What Is Chronic Hiv Infection

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Natural Hosts Are Able To Resolve Inflammation

Targeting Viral DNA for the Cure of HIV and other Chronic Infections

The rapid control of inflammation in natural hosts had led us to raise the hypothesis that HIV-infected individuals with lower levels of inflammation by the end of acute HIV-1 infection would have a higher probability to become long term non progressors. We have quantified 28 plasma proteins in HIV-1 infected individuals with a known disease progression profile . Already during primary infection, rapid progressors showed a higher number of inflammatory cytokines than progressors or slow progressors. The plasma levels of TGF-1 and IL-18 in acute HIV-1 infection were able to predict 74% of the T-cell activation variation at set-point. Plasma IP-10 was positively and negatively associated with, respectively, T cell activation and CD4+ Tcell counts at set-point and capable of predicting 30% of the CD4+ T-cell count variation. Moreover, plasma IP-10 levels during acute infection were predictive of rapid progression. This study showed for the first time that the inflammatory profile in acute HIV-1 infection is predictive of subsequent T-cell activation levels . It is urgent to identify the mechanism responsible for the resolution of inflammation in natural hosts and to understand how this impacts the maintenance of normal tissue structure and function.

Genotypic Drug Resistance Testing

All persons diagnosed with acute or recent HIV infection should have a genotypic drug resistance test ordered. The laboratory sample for the genotypic drug should be obtained prior to the individual taking their first dose of antiretroviral therapy, but initiation of antiretroviral therapy can occur prior to the availability of the results from the genotypic drug resistance test result. When the genotypic drug resistance result returns, which often takes 3 to 5 weeks, the antiretroviral regimen can be modified, if needed.

Early Immune Response As Predictor Of Disease Progression

Investigators have shown that individuals have qualitatively different immune responses to primary HIV infection. Several research groups have shown that persons with strong initial CD8 T cell responses have lower HIV RNA levels after 6 to 12 months, and subsequently experience a slower progression of their HIV disease . More recently, the importance of the epitope-specific type of CD8 T cell response in controlling HIV has been elucidated. In most persons newly infected with HIV, higher initial HIV RNA levels predict an accelerated course of HIV disease progression, but this correlation is not universal. Similarly, several reports have suggested that development of clinically apparent acute retroviral syndrome portends a faster progression to AIDS. One study found that among 218 African women with HIV-1, a greater set point viral load or greater severity of acute HIV illness predicted faster progression to death .

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Proposed Mechanisms Inducing Chronic Immune Activation

In the previous section, we discussed how extended and generalized chronic immune activation is in the setting of HIV infection. That being established, the next burning question is what mechanisms contribute to chronic immune activation during HIV infection.

Unfortunately, and despite intense research efforts, there is no clear response to this question. Given the complexity of the interaction between HIV and the host immune system, there are multiple molecular and cellular mechanisms by which HIV infection, at least in theory, can induce immune activation. To make things even more complicated, it is possible that several of the proposed mechanisms synergistically contribute to cause aberrant chronic immune activation. Moreover, it is conceivable, and in our opinion very likely, that the relative contribution of the different mechanisms changes significantly in different subsets of HIV-infected individuals, in different phases of HIV-infection , and in naive versus HAART-treated patients. In this section, we discuss the mechanisms that are considered key players in chronic immune activation in the literature . For each of these mechanisms, we summarize the available experimental data supporting or questioning their contribution.

Proposed contributors to HIV-associated chronic immune activation

Racial Sexual And Age

The end of AIDS: HIV infection as a chronic disease

In the United States, the rate of HIV infection is highest in Blacks . The prevalence is also high among Hispanic persons . These increased rates result from socioeconomic factors rather than genetic predisposition.

In the developed world, HIV infection is much more common in males. In 2015, males accounted for 81% of all diagnoses of HIV infection among adults and adolescents in the United States. Among heterosexuals, females are more likely to acquire HIV infection from an infected male than a male is from an infected female, but a large proportion of infections in males are due to homosexual contact, with or without injection drug use. Males are also more likely to acquire HIV infection from injection drug use alone.

Males were also more likely to acquire HIV infection through contaminated blood products for treatment of hemophilia before universal testing of the blood supply was instituted. The risk of HIV exposure from factor VIII concentrates has been virtually eliminated by viricidal treatment of plasma-derived factor VIII concentrates, as well as the introduction of recombinant factor VIII concentrates and the gradual elimination of albumin from the production process used for these products.

In the developing world, HIV infection is equally common in males and females. The primary route of HIV transmission in the developing world is heterosexual contact.

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Ways To Reduce Your Viral Load

When it comes to viruses, in many cases we arent going to eliminate them completely but we can significantly reduce the viral load and that will have a positive impact on our energy and quality of life. Consuming an antiviral diet and adding targeted supplements to your protocol can help reduce your viral load and improve chronic viral infections.

It is also critical to reduce stress, improve sleep quality and reduce your exposure to toxins. You can follow the diet and take the specific supplements but if you are overwhelmed with stress, not sleeping well or in a home that is full of mold than you will not get well. However, if you do your part to improve those areas than these 3 strategies can help you significantly reduce your viral load.

Lack Of Symptoms In Early Stages

ARS is common once a person has HIV. Still, this isnt the case for everyone. Some people have HIV for years before they know they have it. According to HIV.gov, symptoms of HIV may not appear for a decade or longer. This doesnt mean that cases of HIV without symptoms are less serious. Also, a person who doesnt experience symptoms could still transmit HIV to others.

Symptoms in early HIV tend to appear if the rate of cell destruction is high. Not having symptoms can mean that not as many CD4 cells, a type of white blood cell, are killed early on in the disease. Even though a person has no symptoms, they still have the virus. Thats why regular HIV testing is critical to prevent transmission. Its also important to understand the difference between a CD4 count and a viral load.

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Does Hiv Infection Accelerate Aging

Because many of these non-AIDS events are typically associated with aging in the general population, the popular but vague terms âaccelerated agingâ or âpremature agingâ is often used to characterize the new spectrum of HIV-associated diseases, but there are mixed opinions on what defines these terms. There is ongoing debate as to whether HIV-associated diseases which have been associated with aging are simply more common at any given age, or are occurring earlier than expected. In either case, it is well accepted that HIV-infected adults have high burden of co-morbid conditions, including cardiovascular disease, neuropathy, anemia, osteoporosis, liver disease and kidney disease. An index designed to characterize the impact of multi-morbidity in HIV disease on prognosis has been developed and validated . Multi-morbidity, polypharmacy, chronic inflammation, hypercoagulation, and traditional risk factors such as substance abuse are all relatively common in the HIV infected population, and all are linked to greater risk of developing the clinical manifestations of aging in later life in the general population and presumably in the HIV-infected population .

How Is Sarcoidosis Treated

Immune Strategies for Targeting Chronic Viral Infections

Not all people with sarcoidosis require treatment. For instance, doctors may choose to start with monitoring of the condition when people have mild symptoms or because certain treatments may cause unwanted side effects that outweigh their benefits.

Doctors may recommend treatment when the lungs or heart are involved, when the condition causes neurological symptoms, or when symptoms become worse over time.

Common treatments include:

  • Corticosteroids, such as prednisone, which treat inflammation, help to reduce a variety of symptoms and improve function of the lungs and other affected organs
  • Immunosuppressant medications, such as methotrexate or the monoclonal antibody infliximab , which may help to improve lung and other symptoms
  • Anti-malarial medications, such as hydroxychloroquine, which may help to improve skin conditions associated with sarcoidosis
  • Other medications. Clinical trials at Yale are evaluating new treatments, including JAK inhibitors.

During treatment, people will be monitored closely by their doctors. Individuals with sarcoidosis may be evaluated by multiple specialists to help follow the response to treatment in different organs, such as the lungs, eyes, and skin. The condition may recur or require ongoing treatment in some people.

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What Are Viral Infections

A virus is a small infectious agent with genetic material, RNA or DNA, surrounded by a coat of protein, lipid , or glycoprotein. They can only replicate inside the cells of another organism, so they are parasitic. Viruses can infect humans, animals, plants, and microorganisms.

There are more than 400 viruses that can cause infections in your body. When our bodies encounter a virus, our adaptive immune response acts to clear the primary infection. With some viruses, the immune response is not enough to eradicate the virus and it becomes chronic.

Chronic viral infections can result from a variety of viruses . They escape from our immune system by modulating, or regulating, our immune response. These viruses cause persistent infections which may last for life.

Recommended Testing To Diagnosis Acute Hiv

Detection of Acute HIV with Routine Screening for HIV

The HIV testing algorithm recommended by the CDC and APHL, which utilizes a laboratory-based HIV-1/2 antigen-antibody immunoassay as the initial screening test, will detect approximately 80 to 85% of persons with acute HIV infection. With this algorithm, persons with acute HIV would typically have a positive initial screening test with the HIV-1/2 antigen-antibody immunoassay, followed by a negative HIV-1/HIV-2 antibody differentiation immunoassay, and then a positive HIV-1 RNA test . The ability of this routine screening algorithm to detect most persons with acute HIV is one of the primary reasons the CDC now advocates using this HIV testing approach for routine screening. In the situation where the routine screening testing algorithm detects HIV, follow-up antibody testing in 3 to 6 months should be performed to document seroconversion. From a practical standpoint, routine screening for HIV infection using HIV NAT is not practical due to cost considerations.

Testing for Suspected Very Early Acute HIV Infection

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Chronic Hiv Infection With Antiretroviral Treatment

If you take effective HIV treatment, you can live with HIV as a chronic, manageable condition. A chronic health condition is one which continues for a long period of time.

This stage is not included in most descriptions of the stages of infection, which only describe disease progression in the absence of treatment.

However, most people living with HIV who have access to good healthcare are living with HIV as a chronic condition and will continue to do so for the rest of their lives. They are unlikely to fall ill or die as a direct result of HIV.

In order to reach this stage and to remain in it, you need to take HIV treatment and continue to take it, on an ongoing basis. These medications reduce levels of HIV in your body and strengthen the immune system. This usually prevents the symptoms and opportunistic infections described above from occurring.

One of the benefits of effective HIV treatment is that is stops HIV from being passed on. Treatment drastically reduces the amount of HIV in body fluids to the point where there is not enough HIV to transmit the virus to sexual partners.

The chronic infection phase can last for decades. People who start HIV treatment as soon as possible, are able to stick with it and have access to good healthcare are likely to have a similar life expectancy to their peers who dont have HIV.

How Can You Tell If You Have Hiv

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The only way to know for sure if you have HIV is to get tested. You cant rely on symptoms to tell whether you have HIV.

Knowing your HIV status gives you powerful information so you can take steps to keep yourself and your partner healthy:

  • If you test positive, you can take medicine to treat HIV. By taking HIV medicine daily as prescribed, you can make the amount of HIV in your blood very lowso low that a test cant detect it . Getting and keeping an undetectable viral load is the best thing you can do to stay healthy. If your viral load stays undetectable, you have effectively no risk of transmitting HIV to an HIV-negative partner through sex.
  • If you test negative, there are more HIV prevention tools available today than ever before.
  • If you are pregnant, you should be tested for HIV so that you can begin treatment if you’re HIV-positive. If an HIV-positive woman is treated for HIV early in her pregnancy, the risk of transmitting HIV to her baby can be very low.

Use the HIV Services Locator to find an HIV testing site near you.

HIV self-testing is also an option. Self-testing allows people to take an HIV test and find out their result in their own home or other private location. You can buy a self-test kit at a pharmacy or online, or your health care provider may be able to order one for you. Some health departments or community-based organizations also provide self-test kits for free.

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Cellular Sources Of Factors Associated With Chronic Immune Activation

Most of the cytokines involved in chronic immune activation and inflammation during HIV-1 and SIVmac infections can be produced by multiple cell types. Not all of them have been defined. It has been reported that T cells are the major sources of IP-10 TGF- is mostly produced by T-regulatory cells and plasmacytoid dendritic cells are the predominant IFN-I secreting cells, although other cells might serve as another important source in later stages of infection . Blood mononuclear cells from viremic patients produce more TNF- in response to lipopolysaccharide than those from virologically suppressed patients, with M-DC8+ monocytes being predominantly responsible for this overproduction . Excessive production of TNF- could act at mucosal sites to compromise the integrity of the epithelial barrier .

Other cells of the immune system, such as B cells, neutrophils, or natural killer T cells, contribute to the inflammatory or immunosuppressive milieu, as well as secreting chemokines able to modify cellular distributions. Finally, some non-immune cells, such as cervical epithelial cells, are capable of secreting chemokines after exposure to HIV-1 .

Stage : Clinical Latency

In this stage, the virus still multiplies, but at very low levels. People in this stage may not feel sick or have any symptoms. This stage is also called chronic HIV infection.

Without HIV treatment, people can stay in this stage for 10 or 15 years, but some move through this stage faster.

If you take HIV medicine every day, exactly as prescribed and get and keep an undetectable viral load, you can protect your health and have effectively no risk of transmitting HIV to your sexual partner.

But if your viral load is detectable, you can transmit HIV during this stage, even when you have no symptoms. Its important to see your health care provider regularly to get your viral load checked.

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What Is The Outlook For People With Sarcoidosis

More than half of people who have sarcoidosis recover within 2 to 5 years. For such patients, the condition goes into remission and they are unlikely to experience problems again.

In other people, sarcoidosis becomes a chronic condition that may worsen over time. Remaining under the care of a physician may help to relieve symptoms.

About 20% of people with sarcoidosis experience permanent lung damage. Roughly 5% of people with the condition die from respiratory failure caused by excessive scarring to lung tissue.

The Complex Link Between Inflammation And Illness

The Evolution of HIV Infection to a Chronic Inflammatory Disease

While researchers are still struggling to understand the mechanisms that cause these adverse events, a number of studies have enlightened us as to the association between chronic inflammation and illness.

Chief among these was the Strategies for Management of Antiretroviral Therapy trial, which compared the clinical impact of early HIV treatment versus delayed treatment. One of the things that the scientists found was that, after starting therapy, inflammatory markers in the blood declined but never to the levels seen in HIV-negative people. Residual inflammation remained even when viral suppression was achieved, the levels of which were consistent with increasing rates of arteriosclerosis and other cardiovascular disorders.

A related study from the University of California, San Francisco further demonstrated a direct correlation between the thickness of arterial walls in people with HIV and the levels of inflammatory cells in their blood. While individuals on HIV therapy had thinner walls and fewer inflammatory markers when compared to an untreated counterpart, neither approached the “normal” arterial thickness seen in the general population.

Chronic inflammation was seen to have a similar impact on the kidneys, with increased rates of fibrosis and kidney dysfunction, as well as on the liver, brain, and other organ systems.

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