HIV AIDS overview: Difference between revisions
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{{AIDS}} | {{AIDS}} | ||
{{CMG}}; {{AE}} {{SSK}}, {{TarekNafee}} | {{CMG}}; "{{cv}}"; {{AE}} {{SSK}}, {{TarekNafee}}, {{Marjan}} | ||
==Overview== | ==Overview== | ||
'''Acquired immune deficiency syndrome''' ('''AIDS''') is a disease caused by the '''[[HIV|human immunodeficiency virus]] (HIV)''' that leads to the progressive deterioration of the immune system. | '''Acquired immune deficiency syndrome''' ('''AIDS''') is a disease caused by the '''[[HIV|human immunodeficiency virus]] (HIV)''' that leads to the progressive deterioration of the immune system. In the late stages of the condition, individuals become susceptible to [[opportunistic infection|opportunistic infections]] and neoplastic proliferation. HIV is [[Transmission (medicine)|transmitted]] via direct contact of an exposed [[mucous membrane]] or the bloodstream with [[bodily fluid|bodily fluids]] (e.g., [[blood]], [[semen]], [[vaginal fluid]], [[preseminal fluid]], or [[breast milk]]) that contain HIV particles. HIV is a global pandemic; according to UNAIDS an estimated 37.9 million individuals were living with the disease in 2018. Of these, 36.2 million were adults and 1.7 million were children (< 15 years old). An estimated 1.7 million individuals worldwide became newly infected with HIV in 2018. Since the start of the epidemic until 2018, 74.9 million people have become infected with HIV and 32.0 million people have died from AIDS-related illnesses. In 2018, 79% of all people living with HIV knew their HIV status, and about 8.1 million people did not know that they were living with HIV. Although several antiretroviral treatment regimens for HIV exist, they lead to a "functional" cure clearing the [[virus]] from the blood. There is currently no known "sterilizing cure" due to the existence of a "latent reservoir". Still, modern [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]] has significantly decreased the morbidity and mortality associated with the disease. There are two proven cases of HIV sterilizing cure after bone marrow transplant for cancer: the first, initially known as "the Berlin patient" had leukemia and was presented at the 2008 Conference on Retroviruses and Opportunistic Infections. In 2010 the patient identified himself as Timothy Ray Brown; the second patient, called "the London patient" who had Hodgkin's lymphoma and was also submitted to bone marrow transplant, had his case presented at the same conference in 2019. | ||
==Classification== | ==Classification== | ||
Many definitions have been developed for [[epidemiology|epidemiological]] surveillance of HIV/AIDS; these include the ''Bangui definition'' and the ''1994 Expanded World Health Organization AIDS Case Definition''. However, these systems are neither sensitive nor specific for clinical staging. In developing countries, the [[World Health Organization]] staging system for HIV infection and disease, which uses clinical and laboratory data, is widely employed. The [[Centers for Disease Control and Prevention|Centers for Disease Control]] (CDC) Classification System for HIV/AIDS is another primary system used that is chiefly based on [[CD4+ T cells|CD4 T-lymphocyte]] counts. | Many definitions have been developed for [[epidemiology|epidemiological]] surveillance of HIV/AIDS; these include the ''Bangui definition'' and the ''1994 Expanded World Health Organization AIDS Case Definition''. However, these systems are neither sensitive nor specific for clinical staging. In developing countries, the [[World Health Organization]] staging system for HIV infection and disease, which uses clinical and laboratory data, is widely employed. The [[Centers for Disease Control and Prevention|Centers for Disease Control]] (CDC) Classification System for HIV/AIDS is another primary system used that is chiefly based on [[CD4+ T cells|CD4 T-lymphocyte]] counts. There is a further clinical differentiation between having the virus, but not the disease (HIV-positive) or having the disease (any AIDS-defining condition or a CD4+ count below 200 cells/mm<sup>3</sup>). | ||
==Pathophysiology== | ==Pathophysiology== | ||
HIV causes AIDS by depleting [[CD4+]] T helper [[lymphocyte]]s. The [[virus]] is acquired via either sexual contact, exposure to contaminated blood, or [[vertical transmission|mother-to-child transmission]]. Once the [[virus]] is acquired, it disseminates to the majority of lymphoid organs where it enters a period of rapid viral replication. This leads to the acute phase of the infection characterized by a very elevated viral titer and an acute drop in CD4 T-lymphocyte count. As the immune response mounts, viral replication and the CD4 | HIV causes AIDS by depleting the body's supply of [[CD4+]] T helper [[lymphocyte]]s. The [[virus]] is acquired via either sexual contact, exposure to contaminated blood, or [[vertical transmission|mother-to-child transmission]]. Once the [[virus]] is acquired, it disseminates to the majority of [[lymphoid organs]] where it enters a period of rapid [[viral replication]]. This leads to the acute phase of the infection, which is characterized by a very elevated viral titer (viral load) and an acute drop in [[T helper cell|CD4 T-lymphocyte]] count. As the immune response mounts, [[viral replication]] and the [[T helper cell|CD4 T cell]] depletion rate drops. The immune system continues to deteriorate, but at a slower pace. This is known as the chronic phase of HIV infection. The HIV virus causes [[T helper cell|CD4 T cell]] death through a variety of mechanisms, including cytopathic single-cell destruction, syncytia formation, [[autoimmunity]], and superantigen formation. | ||
==Causes== | ==Causes== | ||
AIDS is caused by the human immunodeficiency virus (HIV). HIV is a [[retrovirus]] classified into the family | AIDS is caused by the human immunodeficiency virus (HIV). HIV is a [[retrovirus]] classified into the family ''[[Retroviridae]]'' and the sub-family ''orthoretrovirinae'', that replicate in a host cell through the process of reverse transcription, and the genus ''Lentivirus'', which are known to cause chronic and deadly diseases characterized by long incubation periods. Two main subspecies of HIV exist: HIV-1 and HIV-2. HIV-1 is composed of two copies of single-stranded [[RNA]] enclosed by a conical [[capsid]] comprising the viral protein p24. The genome consists of several major genes that code for structural and functional proteins. These include the ''gag'', ''pol'', ''env'', ''tat'', and ''nef'' genes. Two enzymes that are critical for all [[retroviruses]] are [[reverse transcriptase]], which transcribes the viral RNA into double-stranded DNA and [[integrase]], which integrates this newly formed DNA into the host genome. It is a well-known fact that no two HIV genomes are the same, not even from the same person, causing some to speculate that HIV is a "[[Quasispecies model|quasispecies]]" of a virus. | ||
==Differentiating AIDS from other | ==Differentiating HIV infection and AIDS from other diseases== | ||
Acute HIV infection may be asymptomatic or may cause a mononucleosis-like syndrome. It | Acute HIV infection may be asymptomatic or may cause a [[mononucleosis]]-like syndrome. It must be differentiated from similar diseases that cause [[fever]], [[fatigue]], [[sore throat]], [[myalgia]], and [[lymphadenopathy]] such as [[toxoplasmosis|acute toxoplasmosis]], acute [[CMV]]/[[EBV]] infections, and [[acute viral hepatitis]]. AIDS should be considered in all patients presenting with symptoms of [[immunodeficiency]] or [[opportunistic infections]]. It should be distinguished from various medical states that cause [[immunosuppression]], including [[common variable immune deficiency]] (CVID), [[chemotherapy]] treatment, [[steroid]] therapy, and severe [[malnutrition]]. | ||
==Epidemiology and Demographics== | ==Epidemiology and Demographics== | ||
HIV is a global [[pandemic]]. In | HIV is a global [[pandemic]]. In 2018, an estimated 37.9 million people worldwide were living with the disease. Since the start of the epidemic until 2018, 74.9 million people have become infected with HIV and 32.0 million people have died from AIDS-related illnesses, including approximately 770,000 patients, and 1.7 million people newly infected with HIV in 2018 alone. Over three-fourths of AIDS-related deaths are confined to Sub-Saharan Africa. Despite advances in [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]] (ART) and reduction of both the [[Mortality rate|mortality]] and the [[morbidity]] of HIV infection with regular use of these agents, routine access to ART is not available in all countries. As the end of June 2019, 24.5 million people were receiving ART in the world. | ||
==Risk Factors== | ==Risk Factors== | ||
The majority of HIV infections are acquired through unprotected sexual intercourse. The exposures with the highest risk of contracting disease include contaminated blood transfusions, childbirth, needle sharing, and receptive anal intercourse. | The majority of HIV infections are acquired through unprotected sexual intercourse. The exposures with the highest risk of contracting the disease include contaminated [[blood transfusions]], [[childbirth]], [[needle sharing]], and receptive anal intercourse. In 2016, needle sharing was the cause of aproximately 20% of all new HIV infections. [[Infectivity]] varies throughout the course of the disease and is closely associated with the HIV [[viral load]]. | ||
==Screening== | ==Screening== | ||
The | The primary determinant of the [[morbidity]] and [[mortality]] of HIV infections is adequate [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral therapy]]. For that reason, early detection is essential in improving outcomes. In 2006, the [[Centers for Disease Control]] announced an initiative for voluntary, routine testing of all Americans aged 13–64 during visits to healthcare facilities. An estimated 25% of infected individuals were unaware of their status. Routine [[prenatal]] HIV testing was also recommended for all women as part of their normal gestational screening tests. | ||
==Natural history, complications, and prognosis== | ==Natural history, complications, and prognosis== | ||
There is currently no cure for HIV/[[AIDS]]. HIV infection leads to progressive decline in CD4+ T-lymphocyte count | There is currently no cure for HIV/[[AIDS]]. HIV infection leads to a progressive decline in [[CD4 T cells|CD4+ T-lymphocyte]] count, which increases the risk of succumbing to [[opportunistic infections]] and malignancies. HIV has a variable rate of progression that is determined by specific host and viral factors.The median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals. With the advent of [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|highly active antiretroviral therapy]] (HAART), both [[morbidity]] and [[mortality]] have dramatically decreased. Survival and the rate of [[CD4 T cells|CD4+ T-lymphocyte]]-count recovery is influenced by age, baseline [[CD4 T cells|CD4+ T-lymphocyte]] count, baseline [[viral load]], and initial and sustained viral suppression. In areas where [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|highly active antiretroviral therapy]] is widely available, the development of [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|highly active antiretroviral therapy]] as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected patient to near normal (assuming full compliance with HAART). HIV infection makes individuals highly susceptible to severe [[opportunistic infections]] and [[neoplastic]] disease. Major complications of HIV/AIDS include ''[[Pneumocystis jirovecii]]'' [[pneumonia]], disseminated [[Mycobacterium avium complex]] infection, [[Cryptococcus|cryptococcal meningitis]], [[cytomegalovirus]] [[retinitis]], [[Kaposi sarcoma]], and [[primary CNS lymphoma]]. | ||
==Opportunistic infections== | ==Opportunistic infections== | ||
Major opprtunistic infections characteristic of AIDS include viral infections | Major [[opprtunistic infections]] characteristic of AIDS include such [[viral infections]] as [[CMV retinitis]], mucosal [[HSV]], and [[varicella zoster]]; [[bacterial infections]] such as [[bacillary angiomatosis]], [[tuberculosis]], [[mycobacterium avium complex]], and [[syphilis]]; and [[fungal infections]] such as [[cryptococcosis]], mucocutaneous [[candidiasis]], [[coccidiomycosis]], and [[pneumocystis jirovecii]] [[pneumonia]]. It is important to recognize that the relationship between opportunistic infections (OIs) and HIV infection is bi-directional. HIV causes the [[immunosuppression]] that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs, as well as other co-infections that may be common in HIV-infected persons, such as [[sexually transmitted infections]] (STIs), can adversely affect the natural history of HIV infection by causing reversible increases in circulating [[viral load]], which could accelerate HIV progression and increase the likelihood of transmission of HIV.The widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable. | ||
==HIV Co-infections== | ==HIV Co-infections== | ||
[[Tuberculosis]], [[hepatitis B]] and [[hepatitis C]] are three of the most common co-infections found in patients with HIV owing mostly to their mode of transmission and epidemiological distribution. | [[Tuberculosis]], [[hepatitis B]] and [[hepatitis C]] are three of the most common co-infections found in patients with HIV owing mostly to their mode of transmission and epidemiological distribution. Co-infetions may manifest differently in patients with HIV due to the altered immune response. Accordingly, screening for these infections is recommended in all patients diagnosed with HIV. | ||
==HIV and pregnancy== | ==HIV and pregnancy== | ||
Approximately one | Approximately one in four HIV-positive women are unaware of their disease status, which puts them at high risk of passing the [[virus]] to their children. [[Vertical transmission|Mother-to-child transmission]] is the most common way in which children become infected with HIV. Virtually all AIDS cases in U.S. children are the result of [[Vertical transmission|mother-to-child transmission]]. HIV transmission is reduced from 25% to less than 2% in women taking antiretroviral therapy (ART) before and during birth, and if their babies are given therapy after birth. Accordingly, universal “opt-out” HIV testing is recommended for all pregnant women early in every pregnancy.Triple therapy should be administered to all pregnant women diagnosed with HIV. However, regardless of the [[antenatal]] ART regimen, [[zidovudine]] should be administered to the mother as an [[intravenous infusion]] during [[labor]], and to the [[neonate]] orally for 6 months after birth. | ||
==HIV infection in infants== | ==HIV infection in infants== | ||
The use of ART during pregnancy in HIV-infected women has resulted in a dramatic decrease in the transmission | The use of ART during pregnancy in HIV-infected women has resulted in a dramatic decrease in the rate of transmission to infants, which is currently less than 2% in the United States. The number of infants with AIDS in the United States continues to decline. For infants born to mothers with unknown HIV status, rapid HIV antibody testing of the mother and/or infant is recommended as soon as possible after birth, with immediate initiation of infant antiretroviral [[prophylaxis]] if the rapid test is positive. Virologic assays that directly detect HIV must be used to diagnose HIV infection in infants younger than 18 months. HIV antibody testing cannot establish HIV infection in this age group because maternal HIV antibodies may persist and interfere with the interpretation of a positive HIV antibody test. The treatment of children living with HIV infection is associated with challenges of adherence, [[drug resistance]], reproductive health planning, management of multiple drugs, and long-term complications from HIV and its treatments. | ||
__NOTOC__ | |||
==Diagnosis== | ==Diagnosis== | ||
===Case Definition=== | ===Case Definition=== | ||
AIDS is defined as an the presence of either of the following in a patient with HIV infection: a CD4+ T | AIDS is defined as an the presence of either of the following in a patient with HIV infection: a [[T helper cell|CD4+ T cell]] count below 200 cells/µl, a [[T helper cell|CD4+ T cell]] percentage of total [[lymphocytes]] of less than 15%, or the presence of any of the 27 specified AIDS-defining illnesses. | ||
===History and symptoms=== | ===History and symptoms=== | ||
Acute HIV should be suspected in patients with flu-like or mononucleosis-like symptoms within 2-4 weeks of exposure to HIV virus or participation in high risk behaviors. Important historical questions for patients with diagnosed HIV/AIDS include: most recent CD4 count and viral load | Acute HIV should be suspected in patients with [[flu]]-like or [[mononucleosis]]-like symptoms within 2-4 weeks of exposure to HIV virus or participation in high-risk behaviors. Important historical questions for patients with diagnosed HIV/AIDS include: most recent [[T helper cell|CD4 T cell]] count and [[viral load]], date of testing, previous and current ART regimens and adherence to treatment, prior [[drug resistance]] testing, current [[antibiotic]] [[prophylaxis]], and history of AIDS-defining illnesses. Although a significant proportion of patients are asymptomatic, those who manifest an acute illness present with [[fever]], [[lymphadenopathy]], [[rash]], [[fatigue]], and [[myalgia]]. This stage is usually followed by a clinical latency period throughout which patients may not experience any symptoms. AIDS defines the final stage of HIV infection and indicates significant [[immunodeficiency]]. AIDS classically presents with [[weight loss]], [[night sweats]], [[fatigue]], and symptoms of [[opportunistic infections]] (or AIDS-defining illnesses) such as [[diarrhea]], mucosal sores, [[cough]], and [[cognitive]] and [[neurological]] deficits. | ||
===Physical examination=== | ===Physical examination=== | ||
The physical examination of a patient with HIV/AIDS can be variable depending on the stage of the disease. Physical exam findings may be related to the virus itself or secondary to the opportunistic infections of late disease. Findings include fever, lymphadenopathy, rash, oral thrush, retinal infiltrates, crackles on auscultation, and focal neurologic deficits. | The physical examination of a patient with HIV/AIDS can be variable depending on the stage of the disease. Physical exam findings may be related to the virus itself or secondary to the [[opportunistic infections]] that are characteristic of late disease. Findings include [[fever]], [[lymphadenopathy]], [[rash]], [[oral thrush]], retinal infiltrates, [[crackles]] on [[auscultation]], and focal neurologic deficits. | ||
===Laboratory Findings=== | ===Laboratory Findings=== | ||
Important laboratory tests for the initial evaluation of patients with suspected HIV infection include screening tests with high sensitivity such as ELISA, dot blot, and latex agglutination assays | Important laboratory tests for the initial evaluation of patients with suspected HIV infection include screening tests with high sensitivity such as [[ELISA]], [[dot blot]], and latex agglutination assays; and confirmatory tests with high specificity such as [[Western blot]] assays, P24 antigen assays, and nucleic acid testing. Two surrogate markers, the [[T helper cell|CD4 T cell]] count (CD4 count) and the plasma HIV [[RNA]] [[viral load]], are routinely used to asses immune function and levels of [[viremia]]. Resistance testing is becoming of greater importance in the management of HIV/AIDS patients given the increased resistance to certain antiretroviral agents. | ||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
Cardiac abnormalities observed in patients with HIV include pericardial effusion, myocarditis, [[dilated cardiomyopathy]], and/or endocardial involvement at any stage of the disease. On [[ECG]], patients may exhibit increased heart rate, prolonged QT interval, and non-specific ST-T changes. | Cardiac abnormalities observed in patients with HIV include [[pericardial effusion]], [[myocarditis]], [[dilated cardiomyopathy]], and/or [[endocardial]] involvement at any stage of the disease. On [[ECG]], patients may exhibit [[increased heart rate]], [[prolonged QT interval]], and non-specific ST-T changes. | ||
===Chest X Ray=== | ===Chest X Ray=== | ||
Chest X-ray findings in HIV/AIDS are related to the development of opportunistic lung infections. They include ground-glass infiltrates suggestive of ''Pneumocystis jirovecii'' pneumonia, lobar consolidation, pleural effusions, loculated empyemas, and lymphadenopathy. | Chest X-ray findings in HIV/AIDS are related to the development of [[opportunistic infections|opportunistic lung infections]]. They include ground-glass infiltrates suggestive of ''Pneumocystis jirovecii'' [[pneumonia]], lobar consolidation, [[pleural effusions]], loculated [[empyema|empyemas]], and [[lymphadenopathy]]. | ||
===CT=== | ===CT=== | ||
CT scans of chest are an important | CT scans of the chest are an important aspect of the work-up of HIV patients presenting with [[pulmonary]] symptoms. A CT scan may show similar findings to those observed on [[chest X-rays]], but carry the advantage of having greater sensitivity in the detection of early [[interstitial lung disease]], [[lymphadenopathy]], and [[pulmonary]] [[nodules]]. | ||
===MRI=== | ===MRI=== | ||
MRI is the neuroimaging modality of choice for the work-up of HIV-positive patients with suspected [[CNS disease]]. MRI can aid in the diagnosis of [[primary CNS lymphoma]], [[AIDS dementia complex]], and cerebral [[toxoplasmosis]]. The AIDS-[[dementia]] complex is characterized by [[diffuse]] [[cerebral atrophy]], enlargement of the cerebral ventricles, and diffuse white matter hypoattenuation. Cerebral [[toxoplasmosis]] presents with ring enhancing lesions with surrounding [[edema]] that may closely resemble [[primary CNS lymphoma]]. | |||
==Treatment== | ==Treatment== | ||
__NOTOC__ | |||
===Medical Therapy=== | ===Medical Therapy=== | ||
The primary goal of [[antiretroviral therapy]] (ART) is to reduce HIV-associated [[morbidity]] and [[mortality]]. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of [[plasma]] [[HIV]] [[RNA]] ([[viral load]]) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease | The primary goal of [[antiretroviral therapy]] (ART) is to reduce HIV-associated [[morbidity]] and [[mortality]]. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of [[plasma]] [[HIV]] [[RNA]] ([[viral load]]) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease. Major classes of agents used in the treatment of HIV include: [[Non-nucleoside reverse transcriptase inhibitors]] (NNRTIs), [[nucleoside reverse transcriptase inhibitors]] (NRTIs), [[protease inhibitors]] (PIs), [[fusion inhibitor]]s, [[CCR5]] antagonists, and [[integrase inhibitors]]. All regimens are combinations of at least 3 agents, preferably with 2 NRTIs. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated [[inflammation]] and its associated complications. | ||
===Surgery=== | |||
HIV-infected patients may require surgery to treat infections and diseases associated with the condition. [[Childbirth]] and [[organ transplant]] are two of the many conditions that may necessitate surgery in an HIV-positive patient. | |||
===Primary Prevention=== | ===Primary Prevention=== | ||
There is currently no [[HIV vaccine|vaccine]] or cure for [[HIV]] or AIDS. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called [[post-exposure prophylaxis]] (PEP). | There is currently no [[HIV vaccine|vaccine]] or cure for [[HIV]] or AIDS to date. The only known methods of prevention are based on avoiding exposure to the [[virus]] or, failing that, an [[HIV AIDS medical therapy#Anti Retroviral Therapy (ART)|antiretroviral treatment]] directly after a highly significant exposure, called [[post-exposure prophylaxis]] (PEP). | ||
===Secondary Prevention=== | ===Secondary Prevention=== | ||
Secondary prevention encompasses measures to reduce the complications of [[HIV]] as well as spread of the disease in the population. | Secondary prevention encompasses measures to reduce the complications of [[HIV]] as well as spread of the disease in the population. | ||
===Cost-Effectiveness of Therapy=== | ===Cost-Effectiveness of Therapy=== | ||
HIV and AIDS | HIV and AIDS slow economic growth by destroying human capital. Without proper [[nutrition]], health care, and medicine that is available in developed countries, large numbers of people are falling victim to [[AIDS]]. They will not only be unable to work, but will also require significant and expensive medical care. It is expected that this will likely cause a collapse of economies and societies in certain regions. In some heavily infected areas, the epidemic has left behind many orphans who are cared for by elderly grandparents. | ||
===Future or Investigational Therapies=== | ===Future or Investigational Therapies=== | ||
Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage [[drug resistance]]. | Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage [[drug resistance]]. To learn more about HIV vaccine [[HIV vaccine|click here.]] | ||
[[Category:HIV/AIDS]] | [[Category:HIV/AIDS]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Immune system disorders]] | [[Category:Immune system disorders]] | ||
[[category:viral diseases]] | [[category:viral diseases]] | ||
[[Category:Pandemics]] | [[Category:Pandemics]] | ||
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{{WH}} | {{WH}} | ||
{{WS}} | {{WS}} | ||
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Latest revision as of 15:21, 23 February 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; "Carla Vorsatz, M.D.[2]"; Associate Editor(s)-in-Chief: Serge Korjian M.D., Tarek Nafee, M.D. [3], Marjan Khan M.B.B.S.[4]
Overview
Acquired immune deficiency syndrome (AIDS) is a disease caused by the human immunodeficiency virus (HIV) that leads to the progressive deterioration of the immune system. In the late stages of the condition, individuals become susceptible to opportunistic infections and neoplastic proliferation. HIV is transmitted via direct contact of an exposed mucous membrane or the bloodstream with bodily fluids (e.g., blood, semen, vaginal fluid, preseminal fluid, or breast milk) that contain HIV particles. HIV is a global pandemic; according to UNAIDS an estimated 37.9 million individuals were living with the disease in 2018. Of these, 36.2 million were adults and 1.7 million were children (< 15 years old). An estimated 1.7 million individuals worldwide became newly infected with HIV in 2018. Since the start of the epidemic until 2018, 74.9 million people have become infected with HIV and 32.0 million people have died from AIDS-related illnesses. In 2018, 79% of all people living with HIV knew their HIV status, and about 8.1 million people did not know that they were living with HIV. Although several antiretroviral treatment regimens for HIV exist, they lead to a "functional" cure clearing the virus from the blood. There is currently no known "sterilizing cure" due to the existence of a "latent reservoir". Still, modern antiretroviral therapy has significantly decreased the morbidity and mortality associated with the disease. There are two proven cases of HIV sterilizing cure after bone marrow transplant for cancer: the first, initially known as "the Berlin patient" had leukemia and was presented at the 2008 Conference on Retroviruses and Opportunistic Infections. In 2010 the patient identified himself as Timothy Ray Brown; the second patient, called "the London patient" who had Hodgkin's lymphoma and was also submitted to bone marrow transplant, had his case presented at the same conference in 2019.
Classification
Many definitions have been developed for epidemiological surveillance of HIV/AIDS; these include the Bangui definition and the 1994 Expanded World Health Organization AIDS Case Definition. However, these systems are neither sensitive nor specific for clinical staging. In developing countries, the World Health Organization staging system for HIV infection and disease, which uses clinical and laboratory data, is widely employed. The Centers for Disease Control (CDC) Classification System for HIV/AIDS is another primary system used that is chiefly based on CD4 T-lymphocyte counts. There is a further clinical differentiation between having the virus, but not the disease (HIV-positive) or having the disease (any AIDS-defining condition or a CD4+ count below 200 cells/mm3).
Pathophysiology
HIV causes AIDS by depleting the body's supply of CD4+ T helper lymphocytes. The virus is acquired via either sexual contact, exposure to contaminated blood, or mother-to-child transmission. Once the virus is acquired, it disseminates to the majority of lymphoid organs where it enters a period of rapid viral replication. This leads to the acute phase of the infection, which is characterized by a very elevated viral titer (viral load) and an acute drop in CD4 T-lymphocyte count. As the immune response mounts, viral replication and the CD4 T cell depletion rate drops. The immune system continues to deteriorate, but at a slower pace. This is known as the chronic phase of HIV infection. The HIV virus causes CD4 T cell death through a variety of mechanisms, including cytopathic single-cell destruction, syncytia formation, autoimmunity, and superantigen formation.
Causes
AIDS is caused by the human immunodeficiency virus (HIV). HIV is a retrovirus classified into the family Retroviridae and the sub-family orthoretrovirinae, that replicate in a host cell through the process of reverse transcription, and the genus Lentivirus, which are known to cause chronic and deadly diseases characterized by long incubation periods. Two main subspecies of HIV exist: HIV-1 and HIV-2. HIV-1 is composed of two copies of single-stranded RNA enclosed by a conical capsid comprising the viral protein p24. The genome consists of several major genes that code for structural and functional proteins. These include the gag, pol, env, tat, and nef genes. Two enzymes that are critical for all retroviruses are reverse transcriptase, which transcribes the viral RNA into double-stranded DNA and integrase, which integrates this newly formed DNA into the host genome. It is a well-known fact that no two HIV genomes are the same, not even from the same person, causing some to speculate that HIV is a "quasispecies" of a virus.
Differentiating HIV infection and AIDS from other diseases
Acute HIV infection may be asymptomatic or may cause a mononucleosis-like syndrome. It must be differentiated from similar diseases that cause fever, fatigue, sore throat, myalgia, and lymphadenopathy such as acute toxoplasmosis, acute CMV/EBV infections, and acute viral hepatitis. AIDS should be considered in all patients presenting with symptoms of immunodeficiency or opportunistic infections. It should be distinguished from various medical states that cause immunosuppression, including common variable immune deficiency (CVID), chemotherapy treatment, steroid therapy, and severe malnutrition.
Epidemiology and Demographics
HIV is a global pandemic. In 2018, an estimated 37.9 million people worldwide were living with the disease. Since the start of the epidemic until 2018, 74.9 million people have become infected with HIV and 32.0 million people have died from AIDS-related illnesses, including approximately 770,000 patients, and 1.7 million people newly infected with HIV in 2018 alone. Over three-fourths of AIDS-related deaths are confined to Sub-Saharan Africa. Despite advances in antiretroviral therapy (ART) and reduction of both the mortality and the morbidity of HIV infection with regular use of these agents, routine access to ART is not available in all countries. As the end of June 2019, 24.5 million people were receiving ART in the world.
Risk Factors
The majority of HIV infections are acquired through unprotected sexual intercourse. The exposures with the highest risk of contracting the disease include contaminated blood transfusions, childbirth, needle sharing, and receptive anal intercourse. In 2016, needle sharing was the cause of aproximately 20% of all new HIV infections. Infectivity varies throughout the course of the disease and is closely associated with the HIV viral load.
Screening
The primary determinant of the morbidity and mortality of HIV infections is adequate antiretroviral therapy. For that reason, early detection is essential in improving outcomes. In 2006, the Centers for Disease Control announced an initiative for voluntary, routine testing of all Americans aged 13–64 during visits to healthcare facilities. An estimated 25% of infected individuals were unaware of their status. Routine prenatal HIV testing was also recommended for all women as part of their normal gestational screening tests.
Natural history, complications, and prognosis
There is currently no cure for HIV/AIDS. HIV infection leads to a progressive decline in CD4+ T-lymphocyte count, which increases the risk of succumbing to opportunistic infections and malignancies. HIV has a variable rate of progression that is determined by specific host and viral factors.The median time from infection to the development of AIDS ranges from 8 to 10 years among untreated individuals. With the advent of highly active antiretroviral therapy (HAART), both morbidity and mortality have dramatically decreased. Survival and the rate of CD4+ T-lymphocyte-count recovery is influenced by age, baseline CD4+ T-lymphocyte count, baseline viral load, and initial and sustained viral suppression. In areas where highly active antiretroviral therapy is widely available, the development of highly active antiretroviral therapy as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected patient to near normal (assuming full compliance with HAART). HIV infection makes individuals highly susceptible to severe opportunistic infections and neoplastic disease. Major complications of HIV/AIDS include Pneumocystis jirovecii pneumonia, disseminated Mycobacterium avium complex infection, cryptococcal meningitis, cytomegalovirus retinitis, Kaposi sarcoma, and primary CNS lymphoma.
Opportunistic infections
Major opprtunistic infections characteristic of AIDS include such viral infections as CMV retinitis, mucosal HSV, and varicella zoster; bacterial infections such as bacillary angiomatosis, tuberculosis, mycobacterium avium complex, and syphilis; and fungal infections such as cryptococcosis, mucocutaneous candidiasis, coccidiomycosis, and pneumocystis jirovecii pneumonia. It is important to recognize that the relationship between opportunistic infections (OIs) and HIV infection is bi-directional. HIV causes the immunosuppression that allows opportunistic pathogens to cause disease in HIV-infected persons. OIs, as well as other co-infections that may be common in HIV-infected persons, such as sexually transmitted infections (STIs), can adversely affect the natural history of HIV infection by causing reversible increases in circulating viral load, which could accelerate HIV progression and increase the likelihood of transmission of HIV.The widespread use of ART starting in the mid-1990s has had the most profound influence on reducing OI-related mortality in HIV-infected persons in those countries in which these therapies are accessible and affordable.
HIV Co-infections
Tuberculosis, hepatitis B and hepatitis C are three of the most common co-infections found in patients with HIV owing mostly to their mode of transmission and epidemiological distribution. Co-infetions may manifest differently in patients with HIV due to the altered immune response. Accordingly, screening for these infections is recommended in all patients diagnosed with HIV.
HIV and pregnancy
Approximately one in four HIV-positive women are unaware of their disease status, which puts them at high risk of passing the virus to their children. Mother-to-child transmission is the most common way in which children become infected with HIV. Virtually all AIDS cases in U.S. children are the result of mother-to-child transmission. HIV transmission is reduced from 25% to less than 2% in women taking antiretroviral therapy (ART) before and during birth, and if their babies are given therapy after birth. Accordingly, universal “opt-out” HIV testing is recommended for all pregnant women early in every pregnancy.Triple therapy should be administered to all pregnant women diagnosed with HIV. However, regardless of the antenatal ART regimen, zidovudine should be administered to the mother as an intravenous infusion during labor, and to the neonate orally for 6 months after birth.
HIV infection in infants
The use of ART during pregnancy in HIV-infected women has resulted in a dramatic decrease in the rate of transmission to infants, which is currently less than 2% in the United States. The number of infants with AIDS in the United States continues to decline. For infants born to mothers with unknown HIV status, rapid HIV antibody testing of the mother and/or infant is recommended as soon as possible after birth, with immediate initiation of infant antiretroviral prophylaxis if the rapid test is positive. Virologic assays that directly detect HIV must be used to diagnose HIV infection in infants younger than 18 months. HIV antibody testing cannot establish HIV infection in this age group because maternal HIV antibodies may persist and interfere with the interpretation of a positive HIV antibody test. The treatment of children living with HIV infection is associated with challenges of adherence, drug resistance, reproductive health planning, management of multiple drugs, and long-term complications from HIV and its treatments.
Diagnosis
Case Definition
AIDS is defined as an the presence of either of the following in a patient with HIV infection: a CD4+ T cell count below 200 cells/µl, a CD4+ T cell percentage of total lymphocytes of less than 15%, or the presence of any of the 27 specified AIDS-defining illnesses.
History and symptoms
Acute HIV should be suspected in patients with flu-like or mononucleosis-like symptoms within 2-4 weeks of exposure to HIV virus or participation in high-risk behaviors. Important historical questions for patients with diagnosed HIV/AIDS include: most recent CD4 T cell count and viral load, date of testing, previous and current ART regimens and adherence to treatment, prior drug resistance testing, current antibiotic prophylaxis, and history of AIDS-defining illnesses. Although a significant proportion of patients are asymptomatic, those who manifest an acute illness present with fever, lymphadenopathy, rash, fatigue, and myalgia. This stage is usually followed by a clinical latency period throughout which patients may not experience any symptoms. AIDS defines the final stage of HIV infection and indicates significant immunodeficiency. AIDS classically presents with weight loss, night sweats, fatigue, and symptoms of opportunistic infections (or AIDS-defining illnesses) such as diarrhea, mucosal sores, cough, and cognitive and neurological deficits.
Physical examination
The physical examination of a patient with HIV/AIDS can be variable depending on the stage of the disease. Physical exam findings may be related to the virus itself or secondary to the opportunistic infections that are characteristic of late disease. Findings include fever, lymphadenopathy, rash, oral thrush, retinal infiltrates, crackles on auscultation, and focal neurologic deficits.
Laboratory Findings
Important laboratory tests for the initial evaluation of patients with suspected HIV infection include screening tests with high sensitivity such as ELISA, dot blot, and latex agglutination assays; and confirmatory tests with high specificity such as Western blot assays, P24 antigen assays, and nucleic acid testing. Two surrogate markers, the CD4 T cell count (CD4 count) and the plasma HIV RNA viral load, are routinely used to asses immune function and levels of viremia. Resistance testing is becoming of greater importance in the management of HIV/AIDS patients given the increased resistance to certain antiretroviral agents.
Electrocardiogram
Cardiac abnormalities observed in patients with HIV include pericardial effusion, myocarditis, dilated cardiomyopathy, and/or endocardial involvement at any stage of the disease. On ECG, patients may exhibit increased heart rate, prolonged QT interval, and non-specific ST-T changes.
Chest X Ray
Chest X-ray findings in HIV/AIDS are related to the development of opportunistic lung infections. They include ground-glass infiltrates suggestive of Pneumocystis jirovecii pneumonia, lobar consolidation, pleural effusions, loculated empyemas, and lymphadenopathy.
CT
CT scans of the chest are an important aspect of the work-up of HIV patients presenting with pulmonary symptoms. A CT scan may show similar findings to those observed on chest X-rays, but carry the advantage of having greater sensitivity in the detection of early interstitial lung disease, lymphadenopathy, and pulmonary nodules.
MRI
MRI is the neuroimaging modality of choice for the work-up of HIV-positive patients with suspected CNS disease. MRI can aid in the diagnosis of primary CNS lymphoma, AIDS dementia complex, and cerebral toxoplasmosis. The AIDS-dementia complex is characterized by diffuse cerebral atrophy, enlargement of the cerebral ventricles, and diffuse white matter hypoattenuation. Cerebral toxoplasmosis presents with ring enhancing lesions with surrounding edema that may closely resemble primary CNS lymphoma.
Treatment
Medical Therapy
The primary goal of antiretroviral therapy (ART) is to reduce HIV-associated morbidity and mortality. This goal is best accomplished by using highly-active ART to maximally inhibit HIV replication, as defined by achievement and maintenance of plasma HIV RNA (viral load) below detectable levels, restoration of normal CD4 cell count, and prevention of transmission of the disease. Major classes of agents used in the treatment of HIV include: Non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), fusion inhibitors, CCR5 antagonists, and integrase inhibitors. All regimens are combinations of at least 3 agents, preferably with 2 NRTIs. Durable viral suppression improves immune function and quality of life, lowers the risk of both AIDS-defining and non-AIDS-defining complications, and prolongs life. Based on emerging evidence, additional benefits of ART include a reduction in HIV-associated inflammation and its associated complications.
Surgery
HIV-infected patients may require surgery to treat infections and diseases associated with the condition. Childbirth and organ transplant are two of the many conditions that may necessitate surgery in an HIV-positive patient.
Primary Prevention
There is currently no vaccine or cure for HIV or AIDS to date. The only known methods of prevention are based on avoiding exposure to the virus or, failing that, an antiretroviral treatment directly after a highly significant exposure, called post-exposure prophylaxis (PEP).
Secondary Prevention
Secondary prevention encompasses measures to reduce the complications of HIV as well as spread of the disease in the population.
Cost-Effectiveness of Therapy
HIV and AIDS slow economic growth by destroying human capital. Without proper nutrition, health care, and medicine that is available in developed countries, large numbers of people are falling victim to AIDS. They will not only be unable to work, but will also require significant and expensive medical care. It is expected that this will likely cause a collapse of economies and societies in certain regions. In some heavily infected areas, the epidemic has left behind many orphans who are cared for by elderly grandparents.
Future or Investigational Therapies
Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. To learn more about HIV vaccine click here. Template:WH Template:WS