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Acquired Immunodeficiency Syndrome

Disease Details

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Description: Acquired Immunodeficiency Syndrome (AIDS) is a chronic, potentially life-threatening condition caused by the human immunodeficiency virus (HIV) that severely weakens the immune system, making the body vulnerable to opportunistic infections and certain cancers.
Type: Acquired Immunodeficiency Syndrome (AIDS) is an infectious disease caused by the human immunodeficiency virus (HIV). It is not a genetically transmitted disease. Instead, it is transmitted through specific behaviors and exposures, such as unprotected sexual contact, sharing needles, transfusion of contaminated blood, and from mother to child during childbirth or breastfeeding.
Signs And Symptoms: There are three main stages of HIV infection: acute infection, clinical latency, and AIDS.
Prognosis: HIV/AIDS has become a chronic rather than an acutely fatal disease in many areas of the world. Prognosis varies between people, and both the CD4 count and viral load are useful for predicted outcomes. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. After the diagnosis of AIDS, if treatment is not available, survival ranges between 6 and 19 months. ART and appropriate prevention of opportunistic infections reduces the death rate by 80%, and raises the life expectancy for a newly diagnosed young adult to 20–50 years. This is between two thirds and nearly that of the general population. If treatment is started late in the infection, prognosis is not as good: for example, if treatment is begun following the diagnosis of AIDS, life expectancy is ~10–40 years. Half of infants born with HIV die before two years of age without treatment.
The primary causes of death from HIV/AIDS are opportunistic infections and cancer, both of which are frequently the result of the progressive failure of the immune system. Risk of cancer appears to increase once the CD4 count is below 500/μL. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by a number of factors such as a person's susceptibility and immune function; their access to health care, the presence of co-infections; and the particular strain (or strains) of the virus involved.Tuberculosis co-infection is one of the leading causes of sickness and death in those with HIV/AIDS being present in a third of all HIV-infected people and causing 25% of HIV-related deaths. HIV is also one of the most important risk factors for tuberculosis. Hepatitis C is another very common co-infection where each disease increases the progression of the other. The two most common cancers associated with HIV/AIDS are Kaposi's sarcoma and AIDS-related non-Hodgkin's lymphoma. Other cancers that are more frequent include anal cancer, Burkitt's lymphoma, primary central nervous system lymphoma, and cervical cancer.Even with anti-retroviral treatment, over the long term HIV-infected people may experience neurocognitive disorders, osteoporosis, neuropathy, cancers, nephropathy, and cardiovascular disease. Some conditions, such as lipodystrophy, may be caused both by HIV and its treatment.
Onset: Acquired Immunodeficiency Syndrome (AIDS) is the advanced stage of HIV infection. The onset of AIDS varies greatly among individuals and can take several years to develop after initial HIV infection. Without treatment, it typically progresses to AIDS within 10 years or longer, but with antiretroviral therapy (ART), this progression can be significantly delayed. The onset is marked by a critically weakened immune system, characterized by a CD4 cell count below 200 cells per microliter or the presence of certain opportunistic infections or cancers.
Prevalence: The global prevalence of acquired immunodeficiency syndrome (AIDS) is generally measured by the number of individuals living with HIV, the virus that causes AIDS. As of the most recent data, approximately 37.7 million people globally are living with HIV. Keep in mind that prevalence can vary significantly by region and population.
Epidemiology: HIV/AIDS is considered a global pandemic. As of 2022, approximately 39.0 million people worldwide are living with HIV, the number of new infections that year being about 1.3 million. This is down from 2.1 million new infections in 2010. Among new infections, 46% are in women and are children globally. There were 630,000 AIDS related deaths in 2022, down from a peak of 2 million in 2005.Among persons living with HIV (PLWH), the largest proportion reside in eastern and southern Africa (20.6 million, 54.6%). This region also had the highest rate of adult and child deaths due to AIDS in 2020 (310,000, 46.6%). Sub-Saharan African adolescent girls and young women (aged 15-24 years) account for 77% of new infections among this age-range globally Here, in contrast to other regions, adolescent girls and young women are three times more likely to acquire HIV than age-matched males. Despite these statistics, overall, new HIV infections and AIDS-related deaths have substantially decreased in this region since 2010.Eastern Europe and central Asia has observed a 43% increase in new HIV infections and 32% increase in AIDS-related deaths since 2010, the highest of all global regions. These infections are predominantly distributed in persons who inject drugs, with gay men and other men who have sex with men or persons who engage in transaction sex the second and third populations most impacted in this region.At the end of 2019, United States indicated that approximately 1.2 million people aged ≥13 years were living with HIV, resulting in about 18,500 deaths in 2020. There were 34,800 estimated new infections in the US in 2019, 53% of which were in the southern region of the country. In addition to geographic location, significant disparities in HIV incidence exist among men, Black or Hispanic populations, and men who reported male-to-male sexual contact. The US Centers for Disease Control and Prevention estimated that in that year, 158,500 people or 13% of infected Americans were unaware of their infection.In the United Kingdom as of 2015, there were approximately 101,200 cases which resulted in 594 deaths. In Canada as of 2008, there were about 65,000 cases causing 53 deaths. Between the first recognition of AIDS (in 1981) and 2009, it has led to nearly 30 million deaths. Rates of HIV are lowest in North Africa and the Middle East (0.1% or less), East Asia (0.1%), and Western and Central Europe (0.2%). The worst-affected European countries, in 2009 and 2012 estimates, are Russia, Ukraine, Latvia, Moldova, Portugal and Belarus, in decreasing order of prevalence.Groups at higher risk of acquiring HIV include persons who engage in transactional sex, gay men and other men who have sex with men, persons who inject drugs, transgender persons, and those who are incarcerated or detained.
Intractability: Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV). While there is currently no cure for AIDS, it can be managed with antiretroviral therapy (ART). ART can significantly prolong the lives of those with HIV, reduce the viral load to undetectable levels, and lower the risk of transmission. Thus, while the underlying infection is not curable, the progression and impact of AIDS can be controlled and managed effectively with proper medical treatment.
Disease Severity: Acquired Immunodeficiency Syndrome (AIDS) is considered to be a severe, life-threatening condition. It is the final stage of Human Immunodeficiency Virus (HIV) infection, where the body's immune system is severely damaged, making it difficult to fight off infections and diseases.
Healthcare Professionals: Disease Ontology ID - DOID:635
Pathophysiology: After the virus enters the body, there is a period of rapid viral replication, leading to an abundance of virus in the peripheral blood. During primary infection, the level of HIV may reach several million virus particles per milliliter of blood. This response is accompanied by a marked drop in the number of circulating CD4+ T cells. The acute viremia is almost invariably associated with activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts recover. A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.Ultimately, HIV causes AIDS by depleting CD4+ T cells. This weakens the immune system and allows opportunistic infections. T cells are essential to the immune response and without them, the body cannot fight infections or kill cancerous cells. The mechanism of CD4+ T cell depletion differs in the acute and chronic phases. During the acute phase, HIV-induced cell lysis and killing of infected cells by CD8+ T cells accounts for CD4+ T cell depletion, although apoptosis may also be a factor. During the chronic phase, the consequences of generalized immune activation coupled with the gradual loss of the ability of the immune system to generate new T cells appear to account for the slow decline in CD4+ T cell numbers.Although the symptoms of immune deficiency characteristic of AIDS do not appear for years after a person is infected, the bulk of CD4+ T cell loss occurs during the first weeks of infection, especially in the intestinal mucosa, which harbors the majority of the lymphocytes found in the body. The reason for the preferential loss of mucosal CD4+ T cells is that the majority of mucosal CD4+ T cells express the CCR5 protein which HIV uses as a co-receptor to gain access to the cells, whereas only a small fraction of CD4+ T cells in the bloodstream do so. A specific genetic change that alters the CCR5 protein when present in both chromosomes very effectively prevents HIV-1 infection.HIV seeks out and destroys CCR5 expressing CD4+ T cells during acute infection. A vigorous immune response eventually controls the infection and initiates the clinically latent phase. CD4+ T cells in mucosal tissues remain particularly affected. Continuous HIV replication causes a state of generalized immune activation persisting throughout the chronic phase. Immune activation, which is reflected by the increased activation state of immune cells and release of pro-inflammatory cytokines, results from the activity of several HIV gene products and the immune response to ongoing HIV replication. It is also linked to the breakdown of the immune surveillance system of the gastrointestinal mucosal barrier caused by the depletion of mucosal CD4+ T cells during the acute phase of disease.
Carrier Status: Carrier status does not apply to Acquired Immunodeficiency Syndrome (AIDS). AIDS is a condition caused by the Human Immunodeficiency Virus (HIV). A person can be a carrier of HIV, meaning they are HIV-positive, but they may not necessarily have developed AIDS. The progression from HIV to AIDS depends on various factors, including the effectiveness of treatment.
Mechanism: Acquired Immunodeficiency Syndrome (AIDS) is caused by the Human Immunodeficiency Virus (HIV).

Mechanism:
HIV targets the immune system, specifically the CD4+ T cells, which are crucial for immune response. Once HIV enters the body, it binds to the CD4 receptor and a co-receptor (CCR5 or CXCR4) on the surface of these cells. The virus then fuses with the cell membrane and releases its RNA into the host cell. The RNA is reverse transcribed into DNA by the enzyme reverse transcriptase, which is then integrated into the host's genome by integrase. This integrated viral DNA is termed a provirus, which can remain latent or actively transcribe new viral RNA, leading to the production of new viral particles. These new virions bud from the host cell and infect other CD4+ cells, leading to a progressive decline in CD4+ T cell numbers.

Molecular mechanisms:
1. **Entry and Fusion**: HIV envelope proteins (gp120 and gp41) bind to CD4 and co-receptors on host cells, leading to membrane fusion and viral entry.
2. **Reverse Transcription**: HIV's RNA genome is reverse transcribed into DNA by reverse transcriptase, an error-prone process increasing genetic variability.
3. **Integration**: The newly synthesized viral DNA is transported into the nucleus and integrated into the host cell genome via integrase.
4. **Transcription and Translation**: The proviral DNA is transcribed into mRNA by host RNA polymerase II, and viral proteins are synthesized by the host's ribosomes.
5. **Assembly and Budding**: New viral particles are assembled at the cell membrane and bud off, acquiring a lipid envelope from the host cell membrane, which includes viral glycoproteins necessary for infecting new cells.
6. **Immune Evasion**: HIV evades the immune system through several mechanisms, including high mutation rates, glycan shielding of envelope proteins, downregulation of MHC molecules, and establishment of latent reservoirs.

Over time, the loss of CD4+ T cells impairs the immune response, leading to opportunistic infections and cancers that define AIDS.
Treatment: There is currently no cure, nor an effective HIV vaccine. Treatment consists of highly active antiretroviral therapy (ART), which slows progression of the disease. As of 2022, 39 million people globally were living with HIV, and 29.8 million people were accessing ART. Treatment also includes preventive and active treatment of opportunistic infections. As of July 2022, four people have been successfully cleared of HIV. Rapid initiation of antiretroviral therapy within one week of diagnosis appear to improve treatment outcomes in low and medium-income settings and is recommend for newly diagnosed HIV patients.
Compassionate Use Treatment: Compassionate use treatment for Acquired Immunodeficiency Syndrome (AIDS) refers to the use of experimental drugs or therapies for patients who have no other treatment options and for whom the standard treatments have proven ineffective.

Off-label or experimental treatments for AIDS may include:
1. **Broadly Neutralizing Antibodies (bNAbs)** - Experimental therapies using antibodies that target a wide range of HIV strains.
2. **Gene Editing Techniques** - Methods like CRISPR/Cas9 are being investigated to remove or disrupt HIV DNA within the host genome.
3. **Latency-Reversing Agents** - These drugs aim to activate latent HIV reservoirs, making the virus susceptible to antiretroviral therapy (ART).
4. **Therapeutic Vaccines** - Vaccines designed to boost the immune system's ability to control HIV infection.
5. **Immunomodulators** - Drugs that modify the immune response to enhance the body's ability to fight HIV more effectively.

These therapies are still in various stages of research and clinical trials, and their availability may be restricted to clinical trial settings or through compassionate use programs.
Lifestyle Recommendations: Lifestyle recommendations for individuals with acquired immunodeficiency syndrome (AIDS) include:

1. **Healthy Diet**: Consume a balanced diet rich in fruits, vegetables, whole grains, lean proteins, and healthy fats to support the immune system.
2. **Regular Exercise**: Engage in regular physical activity to maintain muscle mass, improve cardiovascular health, and reduce stress.
3. **Medication Adherence**: Strictly adhere to antiretroviral therapy (ART) as prescribed to manage the virus and boost the immune system.
4. **Avoid Infections**: Practice good hygiene, such as frequent handwashing, safe food handling, and avoiding contact with sick individuals to reduce the risk of infections.
5. **Safe Practices**: Use condoms and practice safe sex to prevent transmission of HIV and other sexually transmitted infections.
6. **Routine Checkups**: Regularly visit healthcare providers for monitoring and management of HIV/AIDS and related conditions.
7. **Mental Health**: Seek support for mental health through counseling, support groups, or therapy to cope with the emotional aspects of living with HIV/AIDS.
8. **Avoid Substance Abuse**: Steer clear of illicit drug use and excessive alcohol consumption, which can compromise the immune system and interfere with medications.
Medication: Acquired Immunodeficiency Syndrome (AIDS) is treated with antiretroviral therapy (ART). The primary medications used in ART include:

1. **Nucleoside Reverse Transcriptase Inhibitors (NRTIs)** - Example: Zidovudine (AZT), Lamivudine (3TC)
2. **Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)** - Example: Efavirenz (EFV), Nevirapine (NVP)
3. **Protease Inhibitors (PIs)** - Example: Lopinavir/Ritonavir (LPV/r), Atazanavir (ATV)
4. **Integrase Strand Transfer Inhibitors (INSTIs)** - Example: Raltegravir (RAL), Dolutegravir (DTG)
5. **Entry Inhibitors** - Example: Maraviroc (MVC), Enfuvirtide (T-20)

These medications are usually taken in combination to effectively manage the virus and prevent progression to AIDS. Regular monitoring and adherence to the prescribed regimen are crucial for treatment success.
Repurposable Drugs: Several drugs initially developed for other conditions have been researched for potential repurposing to treat acquired immunodeficiency syndrome (AIDS). These include:

1. **Chloroquine and Hydroxychloroquine**: Originally antimalarial drugs, they have shown potential in modulating immune responses.
2. **Auranofin**: An anti-rheumatic agent with possible activity in reducing HIV viral reservoirs.
3. **Disulfiram**: Used for treating alcohol dependence, it has been investigated for its ability to activate latent HIV, making it more susceptible to antiretroviral therapy.
4. **Minocycline**: An antibiotic that has shown some promise in reducing HIV replication and inflammation.

Ongoing research continues to evaluate the efficacy and safety of these and other repurposable drugs in the context of AIDS treatment.
Metabolites: Acquired Immunodeficiency Syndrome (AIDS) is not directly associated with specific unique metabolites. However, HIV infection and the progression to AIDS can lead to alterations in normal metabolic processes. For example, individuals with AIDS may experience disruptions in lipid metabolism, glucose metabolism, and amino acid metabolism due to the virus itself and antiretroviral treatments.

Moreover, metabolomic studies might identify various changes in metabolites that reflect the body's response to HIV infection, including increased levels of inflammatory markers or changes in energy metabolism. These metabolic changes can contribute to symptoms such as weight loss, fatigue, and increased susceptibility to opportunistic infections.
Nutraceuticals: Acquired Immunodeficiency Syndrome (AIDS) is a chronic, potentially life-threatening condition caused by the Human Immunodeficiency Virus (HIV). There is limited scientific evidence supporting the efficacy of nutraceuticals specifically for the treatment or prevention of AIDS. Nutraceuticals—products derived from food sources with extra health benefits in addition to the basic nutritional value—may have supportive roles in general health but do not replace antiretroviral therapy (ART), the primary treatment for managing HIV/AIDS.

In terms of nanotechnology, research is ongoing to explore its potential in HIV/AIDS management. Nanotechnology could offer innovative solutions for drug delivery, improving the efficacy and reducing side effects of antiretroviral medications. Nanoparticles can be engineered to target specific cells or tissues, potentially enhancing the precision of drug delivery systems and overcoming some of the limitations of current therapies. However, these applications are still largely in the experimental stages.
Peptides: Acquired Immunodeficiency Syndrome (AIDS) is the advanced stage of HIV infection. Research has explored the use of peptides in the treatment and management of HIV/AIDS. Peptides can act as inhibitors to block viral entry, fusion, or replication. Examples include enfuvirtide, a fusion inhibitor that prevents HIV from entering cells. Nanotechnology is another developing field; nanoparticles can be used to deliver antiretroviral drugs more effectively, potentially enhancing drug stability, targeting specific cells, and reducing side effects. Both peptides and nanotechnology represent innovative approaches with potential to improve HIV/AIDS treatment outcomes.