The stages of HIV infection are acute infection (also known as primary infection), latency, and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, swollen lymph nodes, inflammation of the throat, rash, muscle pain, malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts (fewer than 200 per μL), various opportunistic infections, cancers, and other conditions.
Acute HIV infection, primary HIV infection or acute seroconversion syndrome [1] : 416 is the first stage of HIV infection. It occurs after the incubation stage, before the latency stage, and the potential AIDS succeeding the latency stage.
During this period (usually days to weeks post-exposure) fifty to ninety percent of infected individuals develop an influenza or mononucleosis-like illness called acute HIV infection (or HIV prodrome), [2] [3] the most common symptoms of which may include fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and esophageal sores, and may also include, but less commonly, headache, nausea and vomiting, fatigue, ulcers in the mouth or on the genitals, enlarged liver/spleen, weight loss, thrush, night sweats and diarrhea and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. [4] The duration of symptoms varies, averaging 28 days and usually lasting at least a week. [5]
Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. As a consequence, these primary symptoms are not used to diagnose HIV infection, as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period. [6]
Symptoms and signs of primary HIV infections [6] | Sensitivity [lower-alpha 1] | Specificity [lower-alpha 2] |
---|---|---|
Fever | 88% | 50% |
Malaise | 73% | 42% |
Muscle pain | 60% | 74% |
Rash | 58% | 79% |
Headache | 55% | 56% |
Night sweats | 50% | 68% |
Sore throat | 43% | 51% |
Lymphadenopathy | 38% | 71% |
Joint pain | 28% | 87% |
Nasal congestion | 18% | 62% |
Some of those symptoms (nasal congestion, sore throat) have a sensitivity that is less than (meaning that they are more likely without HIV than with it), and are therefore slight evidence against rather than for HIV, per Bayes' theorem.
A strong immune defense reduces the number of viral particles in the bloodstream, marking the start of secondary or chronic HIV infection. The secondary stage of HIV infection can vary between two weeks and 10 years. During the secondary phase of infection, HIV is active within lymph nodes, which typically become persistently swollen, in response to large amounts of virus that become trapped in the follicular dendritic cells (FDC) network. [7] The surrounding tissues that are rich in CD4+ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4+ CD45RO+ T cells carry most of the proviral load. [8] A small percentage of HIV-1 infected individuals retain high levels of CD4+ T-cells without antiretroviral therapy. However, most have detectable viral loads and will eventually progress to AIDS without treatment. These individuals are classified as HIV controllers or long-term nonprogressors (LTNP). People who maintain CD4+ T cell counts and also have low or clinically undetectable viral load without antiretroviral treatment are known as elite controllers or elite suppressors (ES). [9] [10]
The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are opportunistic infections caused by bacteria, viruses, fungi, and parasites that are normally controlled by the elements of the immune system that HIV damages. [11] These infections affect nearly every organ system.[ citation needed ]
A declining CD4+/CD8+ ratio is predictive of the progression of HIV to AIDS. [12]
People with AIDS also have an increased risk of developing various cancers such as Kaposi's sarcoma, cervical cancer, and cancers of the immune system known as lymphomas. Additionally, people with AIDS often have systemic symptoms of infection like fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss. [13] [14] The specific opportunistic infections that AIDS patients develop depend in part on the prevalence of these infections in the geographic area in which the patient lives.[ citation needed ]
Pneumocystis pneumonia (PCP) (originally known as Pneumocystis carinii pneumonia) is relatively rare in healthy, immunocompetent people, but common among HIV-infected individuals. [15] It is caused by Pneumocystis jirovecii .
Before the advent of effective diagnosis, treatment, and routine prophylaxis in Western countries, it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 cells per μL of blood. [16]
Tuberculosis (TB) is unique among infections associated with HIV because it is transmissible to immunocompetent people via the respiratory route, and it is not easily treatable once identified. [17] Multidrug resistance is a serious problem. Tuberculosis with HIV co-infection (TB/HIV) is a major world health problem according to the World Health Organization: in 2007, 456,000 deaths among incident TB cases were HIV-positive, a third of all TB deaths and nearly a quarter of the estimated 2 million HIV deaths in that year. [18] Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per μL), TB typically presents as a pulmonary disease. In advanced HIV infection, TB often presents atypically with extrapulmonary (systemic) disease a common feature. Symptoms are usually constitutional and are not localized to one particular site, often affecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system. [19]
Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV-infected individuals, this is normally due to fungal (candidiasis) or viral (herpes simplex-1 or cytomegalovirus) infections. In rare cases, it could be due to mycobacteria. [20]
Unexplained chronic diarrhea in HIV infection is due to many possible causes, including common bacterial ( Salmonella , Shigella , Listeria or Campylobacter ) and parasitic infections; and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and viruses, [21] astrovirus, adenovirus, rotavirus and cytomegalovirus, (the latter as a course of colitis).
In some cases, diarrhea may be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. It may also be a side effect of antibiotics used to treat bacterial causes of diarrhea (common for Clostridioides difficile ). In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients and may be an important component of HIV-related wasting. [22]
HIV infection may lead to a variety of neuropsychiatric sequelae, either by infection of the now susceptible nervous system by organisms, or as a direct consequence of the illness itself. [23]
Toxoplasmosis is a disease caused by the single-celled parasite Toxoplasma gondii ; it usually infects the brain, causing toxoplasma encephalitis, but it can also infect and cause disease in the eyes and lungs. [24] Cryptococcal meningitis is an infection of the meninx (the membrane covering the brain and spinal cord) by the fungus Cryptococcus neoformans . It can cause fevers, headache, fatigue, nausea, and vomiting. Patients may also develop seizures and confusion; left untreated, it can be lethal.[ citation needed ]
Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the gradual destruction of the myelin sheath covering the axons of nerve cells impairs the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severely weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis. [25]
HIV-associated dementia (HAD) is a metabolic encephalopathy induced by HIV infection and fueled by immune activation of HIV-infected brain macrophages and microglia. These cells are productively infected by HIV and secrete neurotoxins of both host and viral origin. [26] Specific neurological impairments are manifested by cognitive, behavioral, and motor abnormalities that occur after years of HIV infection and are associated with low CD4+ T cell levels and high plasma viral loads.[ citation needed ]
Prevalence is 10–20% in Western countries [27] but only 1–2% of HIV infections in India. [28] [29] This difference is possibly due to the HIV subtype in India. AIDS-related mania is sometimes seen in patients with advanced HIV illness; it presents with more irritability and cognitive impairment and less euphoria than a manic episode associated with true bipolar disorder. Unlike the latter condition, it may have a more chronic course. This syndrome is less frequently seen with the advent of multi-drug therapy.[ citation needed ]
People with HIV infections have substantially increased incidence of several cancers. This is primarily due to co-infection with an oncogenic DNA virus, especially Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV) (also known as human herpesvirus-8 [HHV-8]), and human papillomavirus (HPV). [30] [31]
Kaposi's sarcoma (KS) is the most common tumor in HIV-infected patients. The appearance of this tumor in young homosexual men in 1981 was one of the first signals of the AIDS epidemic. Caused by a gammaherpes virus called Kaposi's sarcoma-associated herpes virus (KSHV), it often appears as purplish nodules on the skin, but can affect other organs, especially the mouth, gastrointestinal tract, and lungs. High-grade B cell lymphomas such as Burkitt's lymphoma, Burkitt's-like lymphoma, diffuse large B-cell lymphoma (DLBCL), and primary central nervous system lymphoma present more often in HIV-infected patients. These particular cancers often foreshadow a poor prognosis. Epstein-Barr virus (EBV) or KSHV cause many of these lymphomas. In HIV-infected patients, lymphoma often arises in extranodal sites such as the gastrointestinal tract. [32] When they occur in an HIV-infected patient, KS and aggressive B cell lymphomas confer a diagnosis of AIDS.[ citation needed ]
Invasive cervical cancer in HIV-infected women is also considered AIDS-defining; it is caused by human papillomavirus (HPV). [33]
In addition to the AIDS-defining tumors listed above, HIV-infected patients are at increased risk of certain other tumors, notably Hodgkin's disease, anal and rectal carcinomas, hepatocellular carcinomas, head and neck cancers, and lung cancer. Some of these are caused by viruses, such as Hodgkin's disease (EBV), anal/rectal cancers (HPV), head and neck cancers (HPV), and hepatocellular carcinoma (hepatitis B or C). Other contributing factors include exposure to carcinogens (cigarette smoke for lung cancer), or living for years with subtle immune defects.[ citation needed ]
The incidence of many common tumors, such as breast cancer or colon cancer, does not increase in HIV-infected patients. In areas where HAART is extensively used to treat AIDS, the incidence of many AIDS-related malignancies has decreased, but at the same time malignant cancers overall have become the most common cause of death of HIV-infected patients. [34] In recent years, an increasing proportion of these deaths have been from non-AIDS-defining cancers.[ citation needed ]
In line with the treatment of cancer, chemotherapy has shown promise in increasing the number of uninfected T-cells and diminishing the viral load. [35]
People with AIDS often develop opportunistic infections that present with non-specific symptoms, especially low-grade fevers and weight loss. These include opportunistic infection with Mycobacterium avium-intracellulare and cytomegalovirus (CMV). CMV can cause colitis, as described above, and CMV retinitis can cause blindness.[ citation needed ]
Talaromycosis due to Talaromyces marneffei is now the third most common opportunistic infection (after extrapulmonary tuberculosis and cryptococcosis) in HIV-positive individuals within the endemic area of Southeast Asia. [36]
An infection that often goes unrecognized in people with AIDS is Parvovirus B19. Its main consequence is anemia, which is difficult to distinguish from the effects of antiretroviral drugs used to treat AIDS itself. [37]
The human immunodeficiency viruses (HIV) are two species of Lentivirus that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs as a strategy to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death. HAART also prevents the transmission of HIV between serodiscordant same-sex and opposite-sex partners so long as the HIV-positive partner maintains an undetectable viral load.
The spread of HIV/AIDS has affected millions of people worldwide; AIDS is considered a pandemic. The World Health Organization (WHO) estimated that in 2016 there were 36.7 million people worldwide living with HIV/AIDS, with 1.8 million new HIV infections per year and 1 million deaths due to AIDS. Misconceptions about HIV and AIDS arise from several different sources, from simple ignorance and misunderstandings about scientific knowledge regarding HIV infections and the cause of AIDS to misinformation propagated by individuals and groups with ideological stances that deny a causative relationship between HIV infection and the development of AIDS. Below is a list and explanations of some common misconceptions and their rebuttals.
AIDS-related lymphoma describes lymphomas occurring in patients with acquired immunodeficiency syndrome (AIDS).
An opportunistic infection is an infection caused by pathogens that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune system, an altered microbiome, or breached integumentary barriers. Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system, and can, in some cases, act as commensals until the balance of the immune system is disrupted. Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.
AIDS-defining clinical conditions is the list of diseases published by the Centers for Disease Control and Prevention (CDC) that are associated with AIDS and used worldwide as a guideline for AIDS diagnosis. CDC exclusively uses the term AIDS-defining clinical conditions, but the other terms remain in common use.
The CDC Classification System for HIV Infection is the medical classification system used by the United States Centers for Disease Control and Prevention (CDC) to classify HIV disease and infection. The system is used to allow the government to handle epidemic statistics and define who receives US government assistance.
Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in some cases of HIV/AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not eradicated. The virus can reactivate and begin producing large amounts of viral progeny without the host becoming reinfected by new outside virus, and stays within the host indefinitely.
Fever of unknown origin (FUO) refers to a condition in which the patient has an elevated temperature (fever) but, despite investigations by one or more qualified physicians, no explanation is found.
The human immunodeficiency virus (HIV) is a retrovirus that attacks the immune system. It can be managed with treatment. Without treatment it can lead to a spectrum of conditions including acquired immunodeficiency syndrome (AIDS). Effective treatment for HIV-positive people involves a life-long regimen of medicine to suppress the virus, making the viral load undetectable. There is no vaccine or cure for HIV. An HIV-positive person on treatment can expect to live a normal life, and die with the virus, not of it.
Idiopathic CD4+ lymphocytopenia (ICL) is a rare medical syndrome in which the body has too few CD4+ T lymphocytes, which are a kind of white blood cell. ICL is sometimes characterized as "HIV-negative AIDS", though, in fact, its clinical presentation differs somewhat from that seen with HIV/AIDS. People with ICL have a weakened immune system and are susceptible to opportunistic infections, although the rate of infections is lower than in people with AIDS.
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) co-infection is a multi-faceted, chronic condition that significantly impacts public health. According to the World Health Organization (WHO), 2 to 15% of those infected with HIV are also affected by HCV, increasing their risk of morbidity and mortality due to accelerated liver disease. The burden of co-infection is especially high in certain high-risk groups, such as intravenous drug users and men who have sex with men. These individuals who are HIV-positive are commonly co-infected with HCV due to shared routes of transmission including, but not limited to, exposure to HIV-positive blood, sexual intercourse, and passage of the Hepatitis C virus from mother to infant during childbirth.
HIV superinfection is a condition in which a person with an established human immunodeficiency virus infection acquires a second strain of HIV, often of a different subtype. These can form a recombinant strain that co-exists with the strain from the initial infection, as well from reinfection with a new virus strain, and may cause more rapid disease progression or carry multiple resistances to certain HIV medications.
The HIV set point is the viral load or number of virions in the blood of a person infected with HIV. HIV infections are broken down into three stages: acute infection, asymptomatic infection, and AIDS. The acute infection stage refers to the first weeks after infection, where the majority of infected individuals display severe flu-like symptoms such as fever, myalgia, sore throat, swollen lymph nodes, arthralgia, fatigue, headache, and sometimes rash. At this stage, viral loads reach high levels and the number of CD4 helper T cells in the blood begins to drop. At this point, seroconversion, the development of antibodies, occurs and the CD4 T cell counts begin to recover as the immune system attempts to fight the virus, marking the HIV set point. The higher the viral load at the set point, the faster the virus will progress to AIDS; the lower the viral load at the set point, the longer the patient will remain in clinical latency, the next stage of the infection. The asymptomatic or clinical latency phase is marked by slow replication of the HIV virus, followed by steady depletion of CD4 T cells with little to no symptoms. For individuals that are rapid progressors, this phase can be short lived, with an average of 2-3 years. Long-term progressors (LTNPS) can remain stable in this stage for over a decade. An uninfected person has 500-1500 CD4 T cells/μL of blood. When this count lowers to less than 500 CD4 T cells/μL, opportunistic infections can occur where the immune system is no longer able to fight pathogens it would have easily cleared in an unimpaired state. The infection progresses to AIDS when the count falls below 200 CD4 T cells/μL, at which point opportunistic infections can be lethal. At this stage, an infected person has 2-3 years of life expectancy. The use of antiretroviral therapy (ART) can greatly slow the progression of the virus to AIDS. The set point is not completely fixed and constant, but can be quite dynamic with significant fluctuations.
Diffuse infiltrative lymphocytosis syndrome (DILS) is a rare multi-system complication of HIV believed to occur secondary to an abnormal persistence of the initial CD8+ T cell expansion that regularly occurs in an HIV infection. This persistent CD8+ T cell expansion occurs in the setting of a low CD4+/CD8+ T cell ratio and ultimately invades and destroys tissues and organs resulting in the various complications of DILS. DILS classically presents with bilateral salivary gland enlargement (parotitis), cervical lymphadenopathy, and sicca symptoms such as xerophthalmia and xerostomia, but it may also involve the lungs, nervous system, kidneys, liver, digestive tract, and muscles. Once suspected, current diagnostic workups include (1) confirming HIV infection, (2) confirming six or greater months of characteristic signs and symptoms, (3) confirming organ infiltration by CD8+ T cells, and (4) exclusion of other autoimmune conditions. Once the diagnosis of DILS is confirmed, management includes highly active antiretroviral therapy (HAART) and as-needed steroids. With proper treatment, the overall prognosis of DILS is favorable.
AntiViral-HyperActivation Limiting Therapeutics (AV-HALTs) are an investigational class of antiretroviral drugs used to treat Human Immunodeficiency Virus (HIV) infection. Unlike other antiretroviral agents given to reduce viral replication, AV-HALTs are single or combination drugs designed to reduce the rate of viral replication while, at the same time, also directly reducing the state of immune system hyperactivation now believed to drive the loss of CD4+ T helper cells leading to disease progression and Acquired Immunodeficiency Syndrome (AIDS).
The Berlin patient is an anonymous person from Berlin, Germany, who was described in 1998 as exhibiting prolonged "post-treatment control" of HIV viral load after HIV treatments were interrupted.
HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.
The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reported that TB is the leading cause of death in those with HIV. In 2019, TB was responsible for 30% of the 690,000 HIV/AIDS related deaths worldwide and 15% of the 1.4 million global TB deaths were in people with HIV or AIDS. The two diseases act in combination as HIV drives a decline in immunity, while tuberculosis progresses due to defective immune status. Having HIV makes one more likely to be infected with tuberculosis, especially if one's CD4 T-cells are low. CD4 T-cells below 200 increases one's risk of tuberculosis infection by 25 times. This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection. The risk of TB generally remains high in HIV-infected patients, remaining above the background risk of the general population even with effective immune reconstitution and high CD4 cell counts with antiretroviral therapy.
It is now known that 50 to 90 percent of patients acutely infected with HIV experience at least some symptoms of the acute retroviral syndrome.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)Seventy-five percent experienced symptoms consistent with acute retroviral syndrome; although 83% sought medical care for these symptoms, only 15% were appropriately diagnosed at that initial medical visit, suggesting opportunities to diagnose these individuals earlier were missed.
{{cite journal}}
: CS1 maint: multiple names: authors list (link)