AIDS

AIDS [ɛɪ̯t͡s] ( acronym of Acquired Immune Deficiency Syndrome , also Acquired Immune Deficiency Syndrome) ^[1] describes a specific combination of symptoms that occur in humans as a result of the destruction of the immune system caused by HIV infection immune system occur. ^[2] Patients develop life-threatening opportunistic infections and tumors .

AIDS was recognized as an independent disease by the US Centers for Disease Control and Prevention (CDC) on December 1, 1981 , based on the definition of the coincidence of certain signs of illness as AIDS . AIDS is one of the sexually transmitted diseases . According to the United Nations Joint Program on HIV/AIDS (UNAIDS), there were approximately 37.9 million HIV-positive people worldwide in 2019. In 2019 there were about 1.7 million new HIV infections (4650 per day) and about 0.77 million people died as a result of HIV/AIDS. 35 million people have died from AIDS since the epidemic began. ^[3]The proportion of people infected with HIV is around 0.8% of the 15 to 49 year olds on a global average, but reaches values ​​of around 25% in individual African countries. ^[4] A vaccination is not available. Due to the more effective treatment of HIV-infected people with new drugs, AIDS has become rarer in Central Europe . ^[5]

Definition and Classification

Classification in the ICD-10

In the globally recognized WHO medical diagnostic classification system ICD-10 , both HIV infection and numerous diseases as a result of HIV infection can be coded. The exact type of secondary disease is encoded in a fourth digit in the version of the ICD-10 most recently updated by the World Health Organization for 2013, for example: B20.6 Pneumocystis pneumonia due to HIV disease .

Classification of HIV infection and AIDS definition

CDC definition

According to the case definitions of the US Centers for Disease Control and Prevention (CDC), a confirmed positive HIV test is considered proof of HIV infection. ^[6] The assessment of HIV infection by degree of severity including AIDS was significantly changed in 2008. Until then, clinical findings and laboratory values ​​were classified separately and presented as a letter-number code. Asymptomatic diseases as well as diseases associated with HIV but not defining AIDS were also included. ^[7] Since 2008, only the AIDS-defining diseases are considered. Classification according to the number of CD4-positive T lymphocytes ( T helper cells) and the list of AIDS-defining diseases remained unchanged.

The letter-number coding, which is still widespread in practice, is therefore outdated. It should be noted that the case definition is primarily used for epidemiological surveillance of HIV and AIDS and not as a guide for clinical diagnostics. A case classification cannot be lowered again; it may therefore say nothing about the current status of a patient.

HIV classification in adults and adolescents* [6]
stage	CD4 + cell count per µl	in percent of all lymphocytes
1	≥ 500	> 29%	and not an AIDS-defining disease
2	200-499	14-28%	and not an AIDS-defining disease
3 (AIDS)	< 200	< 14%	or at least one AIDS-defining disease
unknown	No values		and no AIDS-defining disease finding available
* Proof of HIV infection is required

AIDS is defined as evidence of HIV infection and an AIDS-defining disease (stage 3) or evidence of HIV infection and a CD4 cell count < 200 cells or < 14%. The AIDS-defining diseases/symptoms defined by the CDC are: ^[8]

• Candidiasis (fungal infection) of the bronchi , trachea , or lungs
• Esophageal candidiasis (fungal infection of the esophagus )
• CMV infections (except liver, spleen, lymph nodes)
• CMV retinitis (retinitis with loss of vision )
• Encephalopathy , HIV-related
• Herpes simplex infections: chronic ulcers (lasting > 1 month; or bronchitis, pneumonia, esophagitis)
• Histoplasmosis , disseminated or extrapulmonary
• Isosporiasis , chronic, intestinal, persisting for more than one month
• Kaposi's sarcoma
• Coccidioidomycosis , disseminated or extrapulmonary
• Cryptococcosis , extrapulmonary
• Cryptosporidiosis , chronic, intestinal, > 1 month present
• Burkitt lymphoma
• Lymphoma , immunoblastic
• Lymphoma, primary cerebral
• " Mycobacterium avium complex" or M. kansasii , disseminated or extrapulmonary
• Mycobacteriosis, other or unidentified species disseminated or extrapulmonary
• Pneumocystis pneumonia
• Pneumonias, bacterial recurrent (> two within one year)
• Progressive multifocal leukoencephalopathy
• Salmonella - sepsis , recurrent
• tuberculosis
• toxoplasmosis , cerebral
• Wasting Syndrome (caused by HIV)
• Cervical carcinoma , invasive

European definition

According to the European Commission 's case definition , a confirmed positive HIV test is considered proof of HIV infection. ^{[9] [10]} An assessment of the severity of the HIV infection is not made.

AIDS is defined as evidence of HIV infection and one of the diseases defined in the European case definition for AIDS. These are identical to those of the CDC list (see there). An AIDS diagnosis based solely on laboratory values ​​without any clinical findings (CDC stage 3) was rejected. ^[11]

The European case definition is used for epidemiological surveillance of HIV and AIDS.

WHO definition

According to the WHO case definition, a confirmed positive HIV test is considered proof of HIV infection. ^[12]

Immunological and clinical HIV classification in adults and adolescents* [12]
stage	symptoms	CD4 + cell count per µl % of all lymphocytes
1	Asymptomatic	≥ 500	Asymptomatic disease(s)
2	mild symptoms	350-499	Disease defined for this stage, e.g. B. Herpes zoster
3	Advanced Symptoms	< 350	Disease defined for this stage, e.g. B. Oral hairy cell leukoplakia
4 (AIDS)	Serious Symptoms	<200 <15%	or at least one of the AIDS-defining diseases
* Proof of HIV infection is required

For epidemiological surveillance in adults and adolescents, advanced HIV infection is defined as evidence of HIV infection and clinical stage 3 or 4 disease. ^[12]

In adults and adolescents, AIDS is defined as evidence of HIV infection and an AIDS-defining disease (stage 4) or evidence of HIV infection and a CD4 cell count < 200 cells or < 15%.

The AIDS-defining disorders/symptoms are broadly identical to those in the CDC listing.

transmission

The HI virus is transmitted with the body fluids blood , semen , vaginal secretions , liquor and breast milk . Potential portals of entry are fresh, still bleeding wounds in the mucous membranes (conjunctiva, oral, nasal, vaginal and anal mucosa) or insufficiently keratinized, easily injured areas of the outer skin ( glans , inside of the foreskin of the penis ). The most common routes of infection are unprotected vaginal or anal intercourse , the use of contaminated syringes for intravenous drug use and ingestionOral sex (if mucous membrane contact with semen or menstrual blood). During receptive oral sex with intact oral mucosa, contact with pre- ejaculate or vaginal secretion represents a negligible risk of infection, as does passive oral sex. Men who have sex with men are considered a risk group. How high the risk is during sexual intercourse depends primarily on the viral load in the semen , in the vaginal secretions and in the blood. This is particularly high in the first few weeks after infection, before antibodies have formed, then decreases and increases again in the late stages of the disease.

HIV is not transmitted through saliva , sweat , tears , droplet infection , or through insect bites. Nor does the contamination of intact skin with virus-containing (body) fluid lead to infection. Physical contact in everyday social interactions, the shared use of crockery, cutlery, etc., and the shared use of sanitary facilities do not pose a risk of infection. ^{[13] [14]}

Patients with full-blown AIDS are at risk of infection with typical opportunistic pathogens: viruses of the herpes group , candida , streptococci , pneumococci , meningococci and many others. Partners of patients with full-blown AIDS should also be informed about these pathogens and their routes of infection. For example, the full vaccination protection of contact persons also indirectly reduces the risk for AIDS patients of contracting vaccine-preventable infections. This is especially true for vaccinations that people with immunodeficiency cannot receive. ^{[15] [16]}

Estimated risk of transmission by route of infection ^[17]

route of infection	Risk per 10,000 contacts with an infectious source	In percent
parenterally
blood transfusion	9 250	92.5
Drug injection with used needle	63	0 0.63
pinprick through the skin	23	0 0.23
Sexual (unprotected intercourse)
Anal intercourse, receiving partner	138	0 1.38
Vaginal intercourse, receiving partner	8th	0 0.08
Anal intercourse, introducing partner	11	0 0.11
Vaginal intercourse, introducing partner	4	0 0.04
oral sex	low 1	–
1 Cases of HIV transmission through oral sex have been scientifically documented but are rare. A precise estimate of the risk is not available due to the poor data situation.

Transmission mother/child

The risk of a child being infected by an HIV-infected mother during pregnancy or childbirth is estimated at 10 to 30%. ^[18] If the mother is known to have HIV infection, the risk of transmission to the child can be reduced by giving antiretroviral drugs (to the mother before and to the child after birth), giving birth by cesarean section and not breastfeeding the child be reduced by one percent. ^[13]

However, breastfeeding is recommended in developing countries despite the mother's HIV infection, provided antiretroviral drugs are used to reduce the risk of infection. ^[19] This is because breastfeeding has important advantages over processed foods, especially when they are prepared under poor sanitation conditions or with unclean water, as is often the case in developing countries. In addition, breast milk improves the chances of survival for HIV-infected infants who, for example, were infected before or during birth. ^[20] The WHO therefore recommends exclusive breastfeeding for a period of six months, even for HIV-positive mothers.^[21]

Transmission through blood transfusions

Blood transfusions also carry the risk of HIV infection. However, routine monitoring of blood donations , as is carried out in Germany, greatly reduces this, so that nowadays the risk of contracting an HIV infection via transfusion of a blood product is negligible.

In the first few years after the discovery of HIV (1981), the risk of infection via contaminated blood products was very high, since there were still no reliable laboratory tests for detecting the HI virus to test blood donors. In addition, the risk of infection when infected blood products are transfused is particularly high (approx. 90 percent). People suffering from hemophilia , the bleeding disease, who had to have coagulation factor concentrates transfused regularly, were particularly affected . These clotting factor concentrates were made from numerous plasma donations. As a result, by the late 1980s, approximately 50% of the approximately 15,000 hemophiliacs in the United States were infected with HIV. ^[22]In Germany, too, around 1,800 of the approximately 3,000 hemophiliacs and a further 460 people were infected through blood product transfusions, although there was already the option (albeit very expensive) of virus inactivation of the plasma preparations at that time. ^[23] The "blood scandal" that subsequently developed in the German public sphere ultimately led to the dissolution of the Federal Health Office in 1994 , which had been the supervisory authority for the safety of blood products, by the then Federal Health Minister Horst Seehofer . ^[24] Due to the scandals with HIV or hepatitis C virus-infected blood products, the blood transfusion system in Germany and other countries was subjected to rigorous and strict legal controls. Testing of all blood products for HIV antibodies has been a legal requirement in the USA and Germany since 1985 , which has reduced the risk of infection to significantly less than 1:100,000 (almost all transfusion-related infections occurred before 1985). However, there is still a small residual risk, since antibodies can only be detected a few weeks after the virus infection (“ diagnostic gap ”). Since May 1, 2004, every blood donation in Germany has not only been tested for antibodies, but also directly for the presence of HIV RNArequired by law. In this way, fresh infections can also be detected. The risk of acquiring an HIV infection via an infected blood product was estimated at 1 in 4.3 million or less in Germany in 2008. ^[25]

Transmission through needles/cannulas/needle-sticks

Especially in the early days of the epidemic, many intravenous drug users became infected by sharing hypodermic needles. Doctors and nursing staff also have a certain risk of infection from needlestick injuries in the operating room or after punctures on infected patients. The risk of infection from needle sticks depends very much on the circumstances. The risk of infection is given as an average of 0.3% and increases with the following factors: very deep injuries (16 times higher), visible traces of blood on the needle or the needle was previously in a vein or arteryof the carrier (in each case increased five-fold), with high viral load of the carrier (increased six-fold). The risk with hollow needles is higher than with closed needles.

The risk of sharing a cannula , e.g. B. when injecting heroin to become infected is around 0.7% and decreases with the time interval between injections , but only slowly, since blood trapped in the cannula can remain infectious for days. Although it is generally possible to boil the needles, commercially available needles are often not suitable for this because the plastics used are not heat-resistant. Chemical disinfection with bleach or other disinfectants can significantly reduce the risk, but is not sufficient to reliably rule out transmission. ^{[26] [27]}

Special case – use of non-sterile, reused cutting tools in female genital mutilation

Due to the multiple use of razor blades or other tools in female genital mutilation, also known as female genital mutilation, which often occurs in large numbers within a limited period of time, bacteria and viruses, including HIV, can be transmitted. ^[28] AIDS rates of sometimes more than 20% in the younger population of South African regions indicate the extent of the problem. ^[29]

transmission through sexual intercourse

The individual risk of infection with HIV through sexual intercourse is very variable and depends on many factors. Infection is possible after a single sexual intercourse, but there are also known cases in which no infection occurred despite several years of unprotected sexual contact with an infected partner. Having another sexually transmitted disease at the same time increases the risk of infection by a factor of 5 to 10, and a high viral load of the carrier by a factor of 10 to 30. Newly infected people have a high viral load in the first few weeks because the body does not have any specific antibodies against the HI virus at this stage. Sexual intercourse during menstrual bleedingof the woman is associated with an increased risk of infection for both partners, circumcised men have a lower risk of infection. Overall, the risk of infection does not seem to be constant across the number of contacts, so the risk of individual contacts may be significantly underestimated. With antiretroviral therapy, the risk of transmission decreases significantly due to the falling viral load in the blood and secretions.

• Vaginal intercourse: Unprotected vaginal intercourse is associated with a comparatively high risk (0.05–0.1% per sex act).
• Dry sex : The risk of infection is significantly increased here, as tears and bleeding of the vaginal mucosa are common due to the painful friction and condoms (if used) rarely remain functional in the dry environment. ^{[30] [31]}
• Small tears often appear in the mucous membrane during anal intercourse, which means that the risk is significantly higher compared to vaginal intercourse.
• Fellatio , oral sex with sperm intake through the mouth: The risk of infection is very low, but an infection cannot be ruled out.
• The risk of infection from pre- ejaculate is very small and negligible with oral sex. ^[32]
• Cunnilingus , oral sex in women: The risk is also considered to be extremely low as long as there is no contact with menstrual blood.
• Anilingus : The risk is estimated to be extremely low.
• Other sexual practices that do not involve contact with mucous membranes, blood, semen or vaginal secretions have an extremely low risk of infection.

Post-exposure prophylaxis

After a risk situation, there is sometimes the option of counteracting a possible HIV infection. Such measures include washing the penis after intercourse, squeezing the puncture wounds, and treating with disinfectant . In addition, there is the possibility of drug -based post-exposure prophylaxis (PEP). This offers the best possible protection when treatment is started within two hours of exposure, but may still be effective up to 24 hours after intravenous and up to 72 hours after other exposures via the mucous membranes. ^[18] Therefore, if there is a reasonable suspicion of infection, a doctor should always be consulted immediatelycontacted who can provide information about possible measures and initiate them. The medication for PEP essentially corresponds to the antiretroviral therapy of an HIV-positive patient and usually lasts four weeks.

HIV testing

HIV tests are divided into screening tests and confirmation tests. The aim of a screening test ( e.g. ELISA screening test ) is to detect as many infected people as possible – at the price that some non-infected people are also falsely tested positive. If a person tests positive in the search test, a confirmation test (in Germany and the USA: Western blot confirmation test) is required in many countries to prevent a false positive diagnosis. HIV tests are usually carried out in a laboratory. However, there are also quick tests that can sometimes show a result after just a few minutes without technical aids. ^[33]

An HIV test may only be carried out with the express consent of the person concerned. Testing without the patient's knowledge is not legally permissible and can be prosecuted accordingly.

Anonymized Reporting Obligations

In Germany, the direct or indirect detection of HIV without a name is notifiable according to § 7 paragraph 3 of the Infection Protection Act (IfSG). A positive HIV test must therefore be reported anonymously by the laboratory to the Robert Koch Institute in Berlin ( Section 8 paragraph 1 number 2, 3 or paragraph 4, Section 10 paragraphs 2 and 4 IfSG).

In Austria, only AIDS is notifiable , not just HIV infection . Because an AIDS disease is defined according to the AIDS Act ^[34] if there is evidence of an infection with the HI virus and at least one indicator disease ^[35] ( § 1 AIDS Act). Such an illness and any death caused by it must be reported ( Section 2 of the AIDS Act). The notification must be made to the Ministry of Health in Vienna within one week of the diagnosis being made. However, only the initials (first letter of the first and last name), gender and date of birth and relevant anamnestic and clinical information are to be transmitted (§ 3 AIDS law).

In Switzerland, fulfilled clinical criteria for the disease AIDS and the positive laboratory analysis result for the HI virus must be reported according to the Epidemics Act (EpG) in conjunction with the Epidemics Ordinance and Annex 1 or Annex 3 of the FDHA Ordinance on the Reporting of Transferable Observations human diseases . The doctor, hospital, etc. (only) must report the first name code, place of residence, date of birth, gender, nationality and country of origin, and the laboratory must report (only) the first name code, place of residence, date of birth and gender of the person.

course of the disease

HIV infection has four stages:

acute phase

Two to six weeks after infection, flu-like symptoms such as fever , night sweats , swollen lymph nodes , and nausea can occur.

The most common symptoms of acute HIV infection are (ranked according to the probability of occurrence): ^[36]

• 80% fever
• 78% exhaustion , tiredness
• 68% malaise , feeling sick
• 54% headaches
• 54% loss of appetite
• 54% arthralgia (joint pain)
• 51% rash
• 51% night sweats
• 49% myalgia (muscle pain)
• 49% nausea
• 46% diarrhea (diarrhea)
• 46% fever and rash (as a combination)
• 44% pharyngitis or dysphagia
• 37% oral ulcerations (mouth ulcers)
• 34% Stiff neck (probably due to the swollen lymph nodes also located there)
• 32% weight loss greater than 2.5 kg
• 24% photophobia

However, some patients do not notice the above symptoms, or they do not have them. Since the symptoms are very unspecific and can have many other causes, HIV infections often go undetected at first. An HIV-positive diagnosis cannot be made solely on the basis of symptoms of the acute phase, but only by means of an HIV test.

A positive HIV RNA test by RT-PCR and a negative or “borderline” confirmatory test are used to diagnose an acute HIV infection. ^[36] HIV infections six weeks or more in the past are usually diagnosed using antibody/antigen screening tests rather than PCR.

latency period

During this time, the virus multiplies in the body. Those affected, if they know about their infection, suffer at best psychologically, but physical symptoms often do not appear. Meanwhile, the number of CD4 ⁺ helper cells usually decreases continuously until a severe immune deficiency develops (< 200 CD4 ⁺ cells/microliter). ^[37] The latency period lasts on average nine to eleven years. There are patients who develop AIDS within months of being infected, as well as those who, despite being infected in the 1980s and without antiretroviral therapy , have not progressed to AIDS to date. ^[38]

AIDS-Related Complex (ARC)

This term was formerly used for clinical stage B of the CDC classification (that is, the occurrence of clinical symptoms that do not belong to the AIDS-defining diseases). If left untreated, the transition to the full AIDS picture follows. ^[39]

disease phase

The diagnosis of AIDS is made when an HIV-positive person has certain infections or malignancies called AIDS-defining diseases ( CDC classification 3). These include particularly opportunistic infections caused by viruses , bacteria , fungi or parasites , e.g. B. oral thrush , herpes , pneumococcal or meningococcal infections. Some of these can be prevented with vaccinations . ^{[15] [16]} There are also other diseases such as Kaposi's sarcoma ,malignant lymphoma , HIV encephalopathy and wasting syndrome .

For the (intact) immune system of a healthy person, opportunistic pathogens are usually harmless. However, the compromised immune system of an HIV-positive person cannot adequately ward off the pathogens; the infections mentioned above occur. If left untreated, they are often fatal. The number of T-helper cells in the blood of an HIV-infected person serves as a measure of the destruction of the immune system.

therapy

The indication for treatment of an HIV infection results from clinical findings (HIV-associated symptoms and diseases, opportunistic infections), immune status (CD4-positive T helper lymphocytes) and viral dynamics (HI viral load) in the infected patient. ^[40]

Highly Active Antiretroviral Therapy (HAART)

Highly active antiretroviral therapy (HAART) is the drug combination therapy of at least three antiretroviral agents . The aim of HAART is to reconstitute the immune system and prevent the onset of the AIDS syndrome. A successful HAART pushes the viral load (concentration of the HI virus) ^[41] in the blood below the detection limit, whereupon the number of CD4 ⁺-cells increases again, strengthening the immune system against opportunistic infections and other AIDS-defining diseases. Since the virus quickly develops resistance to individual active ingredients, therapy using three antiretroviral active ingredients has become established. With current drugs, these three active ingredients are combined in one tablet that is taken once a day.

Antiretroviral therapy can significantly increase the life expectancy of HIV-infected people, but cannot completely eradicate the virus - and thus not bring about a cure. In addition, sometimes serious side effects can occur, which can usually be counteracted by changing the combination of active ingredients. Once started, ART should not be discontinued to prevent resistance development. For the same reason, regular tablet intake is essential (see Adherence ).

Basic combinations (nucleoside/nucleotide combinations such as tenofovir/emtricitabine or abacsavir/lamivudine) have been (2009) combined with an NNRTI (such as efavirenz or nevirapine) or a PI (such as atazanavir, fosamprenavir, lopinavir or saquinavir) for initial therapy. ^[42]

Due to new medical study results as well as the development and approval of new antiretroviral drugs and substance classes, HAART is in a continuous development process. Nevertheless, there are clear guidelines at national, ^{[43] [44]} European ^[45] and international ^[46] level on the various aspects of antiretroviral therapy. Several drug classes are currently used: nucleoside and nucleotide analogues (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), HIV protease inhibitors (PI), entry and fusion inhibitors as well asintegrase inhibitors .

The criteria for the best time to start HAART are defined in the respective national guidelines. They weigh the risk of contracting AIDS against the risks of possible long-term toxicity and the development of resistance.

The European recommendation at the start of therapy takes into account three factors: the patient's clinical picture, his CD4 ⁺ value and the viral load.

HAART is strongly recommended for patients who already have AIDS-defining diseases (CDC C). HAART is also recommended in the presence of diseases that indicate a weakened immune system but are not AIDS-defining (CDC B). This also applies to patients who are symptom-free but whose CD4 ⁺ cell count is below 350. It is also recommended that HAART be started in patients with a CD4 ⁺ between 350 and 500 when the viral load is high (>100,000).

Due to the far-reaching consequences for the patient, the decision is made individually so that the patient is sufficiently informed about the risks and side effects and is mentally prepared for the therapy.

active ingredients

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Nucleoside analogues , also known as nucleoside reverse transcriptase inhibitors (NRTI, colloquially “nukes”), act on reverse transcriptase , an enzyme in the HI virus that “translates” the viral RNA genome into double-stranded DNA. Another viral enzyme, integrase , then incorporates this viral DNA into the human host cell's DNA. The NRTI represent an alternative substrate and compete with the physiological (“endogenous”) nucleosides , but differ from them in a modified sugar molecule. The incorporation of the NRTI hinders the structure of the double-strand bond and therefore leads to chain breaks in the viral DNA.

The active ingredients zidovudine (azidothymidine, AZT) and stavudine (d4T) correspond to the DNA building block thymidine , lamivudine (3TC) to cytidine , while didanosine (ddl) is a guanosine analogue, analogous to inosine and abacavir . A combination of analogues with the same starting point (e.g. AZT and d4T) does not make sense.

Numerous side effects can occur during therapy with NRTIs. Headaches , gastrointestinal complaints, a feeling of fullness or nausea, vomiting and diarrhea as well as general tiredness are common. Lactic acidosis (a build-up of lactic acid in the blood), myelotoxicity (bone marrow damage), damage to peripheral nerves and inflammation of the pancreas can occur as a result of prolonged use . Lipodystrophy , a rearrangement of body fat that can also be observed during therapy with HIV protease inhibitors, can also occur if NRTIs are taken for a long time.

Many of these side effects are a result of mitochondrial toxicity : mitochondria , which are responsible for providing energy in cells, also need nucleosides. The incorporation of NRTIs instead of nucleosides leads to metabolic disorders and degeneration of the mitochondria. ^[47] There are significant differences in the toxicity of the individual substrates.

NRTI are taken up unchanged into the cell and activated there by phosphorylation . They are mainly eliminated via the kidneys (renal) and therefore have little interaction with drugs that are metabolized in the liver.

Other NRTIs are emtricitabine and tenofovir . ^[48]

Non-nucleoside reverse transcriptase inhibitors (NNRTI)

While NRTIs inhibit reverse transcriptase as “wrong” building blocks, nonnucleoside reverse transcriptase inhibitors (NNRTI) bind directly to this enzyme, close to the substrate binding site for nucleosides. There are currently three NNRTIs on the market: nevirapine (NVP), delavirdine (DLV), and efavirenz (EFV). While nevirapine and efavirenz are about equally effective, delavirdine hardly plays a role in therapy and is not (yet) approved in Germany. Another NNRTI is etravirine .

As a single substance, NNRTIs show only a limited effect; in combination therapy with two NRTIs, they are equivalent to HIV protease inhibitors from an immunological-virological point of view. So far, no study has been able to show that survival time is improved and the disease progresses more slowly than with HAART. ^[49] However, an improvement in quality of life has been described. ^[50] Only studies on improved CD4 ⁺ cell counts and lower viral loads were used for approval ( surrogate marker studies). Due to their good tolerability and the lower number of pills, they are often preferred to HIV protease inhibitors. NNRTIs are quite sensitive: even a point mutationsufficient to induce resistance of the virus to the active substance. In addition, there are cross-resistances: If a virus shows resistance to an NNRTI, all NNRTIs are usually ineffective. NNRTIs are metabolized in the liver ( cytochrome P450 system).

The side effect profiles of the individual active ingredients differ significantly. In therapy with nevirapine, the main focus is on allergic reactions and liver toxicity. A rash occurs in up to 20% of patients and leads to discontinuation of nevirapine in 7%. To reduce the risk of allergies, nevirapine is given at a low dose at the beginning of therapy. The dose is then gradually increased. Liver toxicity is a rare but potentially life-threatening side effect of nevirapine. Therefore, the liver values ​​(especially the transaminases ) should be closely monitored at the beginning of therapy .

The side effects of efavirenz, on the other hand, primarily affect the central nervous system . They usually occur at the beginning of therapy and then subside. During the first four weeks of a study, two-thirds of the patients experienced dizziness , nearly half experienced nightmares , and about a third experienced light-headedness and difficulty sleeping. However, these tend to decrease over time. While nevirapine is used to prevent mother-to-child transmission ( PMTCT  = Prevention of Mother-to-Child Transmission), efavirenz is contraindicated in pregnancy. In view of the effect on the central nervous system, the roadworthiness is questionable. An advantage of efavirenz over nevirapine is reduced liver toxicity.

Delavirdine is inferior to the other active substances because of the high number of pills and the fact that it is taken three times a day. In addition, it is currently not approved for the German market.

Protease Inhibitors (PI)

If the HIV enzyme HIV protease cannot cleave the viral macromolecule gag-pol polyprotein , non-infectious virus particles are produced. HIV protease inhibitors (such as atazanavir , darunavir , fosamprenavir , indinavir , nelfinavir , saquinavir , and tipranavir ^[51]) were modeled with the knowledge of the molecular structure of the enzyme in such a way that they can bind directly in the active site of the protease. The good efficacy of HIV protease inhibitors has been demonstrated using clinical endpoints. They have contributed to a significant improvement in therapy. ^[52] In long-term treatment, however, there are some problems that can lead to disturbances in lipid metabolism and subsequently lipodystrophy (disorders of fat distribution) and dyslipidemia (elevated blood lipid levels). The reason probably lies in the mitochondrial toxicity, since HIV protease inhibitors apparently damage the mitochondria in a similar way to the NRTI. ^[47]Other side effects are gastrointestinal complaints.

The breakdown of HIV protease inhibitors takes place in the liver by the cytochrome P450 enzyme system. The HIV protease inhibitor ritonavir (RTV) inhibits this system. A move has therefore been made to co-administer other protease inhibitors with ritonavir to slow degradation and increase plasma half-life. This is called a "booster". There is now the HIV protease inhibitor lopinavir (LPV/r) combined with a booster dose of ritonavir. ^[53] This results in an almost 100-fold greater plasma concentration of lopinavir and a greater barrier to resistance. Therefore, lopinavir/ritonavir (trade name Kaletra ) is mostly used after other medications have failed (“salvage range”).

Another problem is the interaction of HIV protease inhibitors with many other substances: on the one hand via the cytochrome P450 enzyme system with components of grapefruit, on the other hand there is a mutual interaction (both mutual weakening and mutual strengthening) with estrogen, which leads to the simultaneous Use of HIV protease inhibitors and hormonal contraceptives prevented. ^[54]

entry inhibitors

Entry inhibitors interrupt the entry of the virus into the host cell.

Fusion Inhibitors (FI)

In early 2003, the first fusion inhibitor , enfuvirtide (ENF, developed under the name T-20 ) was brought to market. T-20 binds to the transmembrane protein gp41, which is important for the fusion of the virus with the cell membrane of the T helper cells, and thus blocks the entry of the virus into the cell. The substance is particularly interesting because it does not trigger any mitochondrial toxicity and thus no lipodystrophy syndrome.

At 36 amino acids, T-20 is too large to be taken orally. In its current form, T-20 must be injected subcutaneously or administered via an IV pump every day. Skin irritation at the puncture site is a common side effect.

Initial studies have shown that simply adding T-20 to traditional antiretroviral therapy has limited success. However, two large studies comparing T-20 to optimized HAART versus optimized HAART without T-20 showed significantly better scores in the T-20 arm of the study. This suggests that those patients who have other drug options will benefit most from T-20. ^[55]

Apparently, T-20 can lead to interactions with granulocytes, which lead to increased infections in some patients.

Rapid resistance development of the virus is also quite likely. However, viral adaptation to the human host of the resistant strains appears to be reduced.

Nevertheless, T-20 gives patients who have to change their therapy due to side effects or resistance an option. However, T-20 is not the first choice at the start of therapy, and not just because of the study situation. According to the manufacturer F. Hoffmann-La Roche AG , T-20 is one of the most complex substances to produce in the company's history. This is reflected in the price, which is more than 24,000 euros per year, higher than some triple combinations of conventional antiretroviral drugs.

Furthermore, since spring 2007 there has been maraviroc (MVC) in the expanded access program for the final treatment of HIV patients who no longer have any other treatment options.

Research is being done on other fusion inhibitors and on a weekly T-20 injection.

Integrase Inhibitors (II)

After many failures and difficulties in the 1990s, the development of integrase inhibitors began to gain momentum in the 2000s. At that time, the principle of strand transfer inhibition was discovered. ^[56] Since 2005, there has also been rapid progress in clinical studies, at the latest after the first data from the phase III studies on raltegravir (MK-0518) integrase inhibitors are the next new group of substances in HIV therapy. MK-0518 is now approved in the Expanded Access Program, i.e. for the final treatment of HIV patients who otherwise have no other treatment options. ^[57]

CCR5 coreceptor inhibitors (CCR5I)

• Maraviroc (see above) ^[58]

monoclonal antibody

In March 2018, the FDA approved the first HIV-1 inhibitor and long-acting monoclonal antibody Ibalizumab-uiyk ( Trogarzo ; manufacturer TaiMed Biologics , Taiwan and Theratechnologies , Canada) for the treatment of those patients who are "multi-resistant" to treatment with all of the above treatment regimens are. The FDA approved the submission under Fast Track , Priority Review , and Breakthrough Therapy . Trogarzo also received the orphan drugStatus that provides incentives to support and encourage the development of drugs for orphan diseases. ^{[59] [60] [61]}

Experimental therapies

maturation inhibitors

Maturation inhibitors (“maturation inhibitors”) inhibit the budding of new virions . As with integrase inhibitors, an antiretroviral effect was demonstrated in vivo for the first time in 2005. Bevirimat (PA-457) is a derivative of betulinic acid , which can be isolated as a triterpene carboxylic acid from birch or plane tree bark and is used as a cytostatic against melanoma . PA-457 inhibits the budding or maturation of new virions. ^[62] Phase IIa studies have already been published. ^[63]Phase IIb trials are sluggish due to unexpected difficulties in dose finding. ^[64]

Tre recombinase

Researchers from the Heinrich Pette Institute in Hamburg, the Leibniz Institute for Experimental Virology and the Max Planck Institute for Molecular Cell Biology and Genetics in Dresden are working with the promising approach of specifically cutting out the HIV genome from the DNA of infected host cells and thus the infection of these cells to undo. To do this, they have developed a special enzyme – Tre recombinase – that acts as “gene scissors”. The enzyme is only activated in the presence of the proviral DNA, i.e. only in infected cells. In 2013, after several promising experiments in vitro ^[65] , scientists succeeded in producing “humanized” ^[66]To rid mice of HIV and thus “cure” them. However, these transgenic mice carried the gene for the Tre recombinase in their genome from the start. ^[67] Whether an efficient therapy for HIV infections or a cure can be developed with the help of the Tre recombinase cannot yet be estimated. The researchers hope to be able to investigate the effectiveness of the Tre recombinase in humans as part of a clinical study in the near future .

Monoclonal Antibodies

A single dose of a multi-antibody cocktail was effective for an average of 56 days in infected rhesus monkeys. Some animals remained healthy afterwards. ^[68]

stem cell transplant

In early 2013, a paper gave hope for a cure, showing that long-term viral reduction followed by hematopoietic stem cell therapy might eradicate HIV completely. ^[69] This seemed to work for the time being, but both patients treated in this way in Boston suffered a recurrence after a few weeks without the virus and now have to be treated with antiretrovirals again. ^[70] While the American Timothy Ray Brown , who also received a stem cell transplant, is still the first healed AIDS patient. ^{[71] [72]}

gene therapy

Partial removal of the coreceptor CCR5 from the genome of the CD4-positive T cells using adoptive cell transfer and genome editing can slow down the drop in the concentration of CD4-positive T cells. ^[73]

prevention

Prevention is the most effective measure against HIV. In general, contact with foreign blood and sperm should be avoided. Through the use of condoms (also femidoms and sachets ), sterile needles when taking drugs , getting piercings , tattoos and other bloody methods of body modification as well as in the medical field as well as a strict blood control in the context of blood donations one can become a evade infection very safely. Caution is also required with methods that cause wounds in the field of BDSM . The UNESCOstarted EDUCAIDS , a worldwide program to educate the population in 2004. Pre- exposure prophylaxis (PrEP) is also used successfully ^[74] as a preventive measure, in which HIV-negative people take antiretroviral HIV therapy drugs to protect themselves from a possible HIV infection. After an event with a risk of infection, the probability of infection can be reduced if so-called post- exposure prophylaxis is carried out.

A sufficiently effective HIV vaccine does not yet exist. The high mutation rate of the HI virus has so far failed many years of research into vaccines that are supposed to promote the formation of protective antibodies against the surface protein gp120. When the drug was successfully tested against the very similar SIV (SI virus, simian immunodeficiency virus) of monkeys, the HI virus had changed the structure of its gp120 surface protein in the wild.

Prophylaxis of opportunistic infections

The Standing Committee on Vaccination (STIKO) at the Robert Koch Institute (RKI) classifies people with an immune deficiency caused by the HI virus as a risk group for opportunistic infectious diseases. They fall ill more often than people with a healthy immune system and also suffer more severe courses. The STIKO therefore advises those affected to keep the age-appropriate standard vaccinations complete and up to date. Since the immune response can be weakened by the AIDS infection, vaccinations should be carried out if possible after the immune system has been stabilized using antiretroviral therapy. If necessary, booster vaccinations are necessary for the vaccination to be successful. ^{[16] [75]}For a number of indication vaccinations, STIKO has published application instructions together with various medical specialist societies. Inactivated vaccines in particular are considered to be well tolerated by immunocompromised patients. These vaccines include vaccines against influenza , herpes zoster , pneumococci and meningococci of serogroups A, C, W, Y and B. Live vaccines e.g. B. against mumps, measles, rubella , varicella or rotavirus, are contraindicated depending on the CD4 value and should only be given after an individual risk-benefit assessment by the doctor treating you. ^{[15] [16]}

The indication for primary prophylaxis of opportunistic infections depends on the extent of the immunosuppression . CD4 thresholds above which certain HIV-associated diseases are unlikely:

• below 50/µl: CMV retinitis, cryptosporidiosis and atypical mycobacteriosis ( MOTT )
• below 100/µl cerebral toxoplasmosis, HIV encephalopathy, cryptococcosis and miliary tuberculosis
• below 250/µl Pneumocystis jirovecii pneumonia, thrush esophagitis and progressive multifocal leukoencephalopathy
• below 350/µl zoster caused by herpes zoster virus, ulcers caused by herpes simplex virus (HSV) and oral thrush
• without limit of the threshold: Kaposi's sarcoma, pulmonary tuberculosis and bacterial pneumonia and meningitis

In contrast to primary prophylaxis, which depends on the CD4 cell count, secondary prophylaxis or post-exposure prophylaxis (see also post- exposure prophylaxis ) is carried out as maintenance therapy after the disease has already gone through:

• Administration of cotrimoxazole after pneumonia caused by Pneumocystis jirovecii (PCP) and toxoplasmosis
• Isoniazid (INH) in patients at risk after tuberculosis
• Azithromycin after atypical mycobacteriosis
• Pneumococcal vaccination after bacterial pneumonia
• Exposure prophylaxis after infection with cryptosporidia (avoid drinking tap water)
• no primary prophylaxis recommended (status: 2009) after CMV retinitis, candidiasis, HSV , varicella zoster virus and cryptococci ^[76]

epidemiology

The prevalence is 0.0059 worldwide, 0.0007 in Germany and 0.0011 in Austria (as of 2006).

General

Global statistics of the HIV/AIDS epidemic

Year	People living with HIV	new infections	deaths	people under therapy	source
2000	28.9 million	3.2 million	1.5 million	0.8 million
2005	31.8 million	2.5 million	2.0 million	2.2 million
2010	33.3 million	2.2 million	1.5 million	7.5 million
2011	33.9 million	2.2 million	1.4 million	9.1 million
2012	34.5 million	2.2 million	1.4 million	11 million
2013	35.2 million	2.1 million	1.3 million	13 million
2014	35.9 million	2.1 million	1.2 million	15 million
2015	36.7 million	2.1 million	1.1 million	17 million
2016	36.7 million	1.8 million	1.0 million	20.9 million	[77]
2017	36.9 million	1.8 million	0.9 million	20.9 million	[78]
2018	37.9 million	1.7 million	0.77 million	23.3 million	[79]
2019	38.0 million	1.7 million	0.69 million	25.4 million	[80]
2020	37.7 million	1.5 million	0.68 million	27.5 million	[81]

From an epidemiological perspective, the global pattern of HIV distribution and its uneven distribution was unusual compared to most other viruses.

The first discovered HI virus was HIV-1, subtype B from the main group M. This virus first appeared around 1925 in Central Africa. ^[82] After genetic analysis of numerous HIV subtypes from all over the world, an international team of researchers came to the conclusion that this virus arrived in Haiti from Africa around 1966 . The investigations also show that there is a high probability that the virus first spread within Haiti and then from there throughout the world. It reached the USA from Haiti in 1969, which could be traced using virus samples from the first known AIDS patients from Haiti. ^[83]In the United States, the virus initially spread very slowly among the heterosexual population, before spreading more rapidly among the high-risk group of homosexual men a little later.

While the HIV epidemic in the US began as early as the 1980s, there were some countries that appeared to be spared from HIV, but were then swept up by the virus at great speed. This was particularly the case in Eastern Europe and Asia in the mid-1990s. In other countries, such as Cameroon , the prevalence of HIV has remained stable for years and then skyrocketed. There does not appear to be an upper limit for HIV prevalence either. For example, the rate of pregnant women with HIV in urban centers in Botswana rose from 38.5% to 55.6% in four years after 1997.

Sustainably successful combating of HIV/AIDS in African high-prevalence countries must include a reduction in both AIDS-related deaths and new infections. Data from some countries hit hard by the HIV epidemic, such as Kenya, Rwanda, Uganda and Zimbabwe, show that there are a number of measures that can reduce the rate of new infections. The foundations of this success are the nationwide introduction of sex education classes, the increasing uptake of antiretroviral therapy, nationwide campaigns to increase condom acceptance, HIV testing with results announced the same day, and self-help kits for sexually transmitted diseases . However, these successes can only be achieved with financial means, which many of theHigh-endemic countries in Africa cannot raise it alone. A political will to actively combat this disease is also indispensable.

According to data from Uganda, the prevalence of HIV in pregnant women has dropped from almost 30% in 1992 to 5.4% in 2007. ^[5] Uganda's success model is not without controversy: Improved data collection and the dramatic mortality rate of people with HIV/AIDS have also contributed to the reduction in HIV prevalence. In Zimbabwe, the prevalence decreased from 29% (1997) to 16% (2007). An interdisciplinary UNAIDS study concluded that the main causal factor was a change in sexual behavior leading to a significant reduction in the number of sexual partners through reductions in extramarital, commercial and casual sex. ^[84]

Worldwide

Southern Africa is still particularly hard hit by the epidemic. In 2012, 70% of all new HIV infections among adults took place here. However, it is evident that the education and prevention programs are successful. Between 2001 and 2012, annual new HIV infections in southern Africa fell by 34%. Globally, new HIV infections fell by 50% or more between 2001 and 2012 in 26 countries, including Ethiopia, Ghana, India, Thailand and Ukraine. On the other hand, there has been an increase in new infections in Eastern Europe and Central Asia as well as the Middle East and North Africa. The country with the highest HIV rate in the world is Swaziland , where 26.5% of adults (aged 15 to 49) were infected with HIV in 2012. ^[4]

Germany

HIV infections in Germany (as of the end of 2018)
(All figures are estimates)

Statistical size	Number
HIV infected	87,900
Of these men	70,600 (80%)
Of these women	17,300 (20%)
Distribution according to risk of infection
Men who have sex with men	54,200 (73.5%)
heterosexually infected	10,900 (14.8%)
Injecting drug users	0 8,200 (11.1%)
Blood products infected	00. 450 (0.6%)
New infections in 2018
In total	0 2,400
Of these men	0 2,000 (80%)
Of these women	00. 400 (20%)
AIDS deaths
Since the beginning of the epidemic	29,200
In 2018	00. 440
Medical care 2018
Estimated number of people who are unaware of their HIV infection	10,600 (5%)
HIV-infected people on antiretroviral therapy	87,900 (93%)
Source: Epidemiological Bulletin Robert Koch Institute 2019

In 1986, the number of new HIV infections peaked at almost 6,000 infections.

In 1987, for example, the Bavarian state government , in the fight against the spread of the HI virus, considered a legislative initiative to tighten up the then federal epidemic law. Compulsory tests for applicants for the public service and prisoners were planned, as well as the expulsion of HIV-positive foreigners and the quarantine of infected people "in special homes". ^{[85] [86]}

In the 1990s, there were around 2,000 new HIV infections each year. From 2000 to 2005, the number of new infections rose steadily each year, particularly among men who have sex with men (MSM). Since 2005, annual new infections seem to have stabilized at around 3,000. In Germany, AIDS is one of the rather insignificant causes of death compared to other causes of death, with around 460 deaths per year . According to data from the Robert Koch Institute (RKI), a total of around 28,100 people in Germany succumbed to the consequences of immune deficiency by the end of 2015. In 2015, an estimated 84,700 people in Germany (about one person in 1000) were infected with HIV. ^[87]The incidence of new infections varies greatly from region to region. In large cities (Berlin, Cologne, Hamburg, Stuttgart, Frankfurt am Main) it was between 10 and 13/100,000 inhabitants in 2012, while it was significantly lower in rural areas. However, an analysis of the number of reports since 2000 shows that, especially among MSM, the number of reports outside of the big cities has increased more than the reports from the big cities and that the numbers are therefore slowly aligning. ^[88] According to the RKI, 10 to 12 percent of MSM in large cities are HIV-positive. ^[89]

According to estimates by the RKI, around 82% of the approximately 3,200 newly infected people in 2015 were men. 64% of those newly infected are men who have sex with men; about 13% of transmissions were through heterosexual intercourse (and counting), 9% of infections through infected syringes associated with injecting drug use, and less than 1% mother-to-child transmissions during pregnancy and delivery. According to estimates, the number of people who are HIV positive in Germany who have not yet been diagnosed is around 12,600. ^[87] The risk of infection for men who have sex with men is therefore significantly higher than for unprotected sex in heterosexual couples. The disease affects all social groups and social classes. ^[90]

The data on the spread of HIV and AIDS determined by the RKI can only be compared with previously published estimates to a limited extent, since additional data and information as well as the adjustment of the survey methodology change the calculations from year to year. The RKI therefore adapts the annual evaluation to the changing data situation and, for example, interpolates data from the early days of the HIV epidemic in order to make an overall trend visible.

The continued rise in other sexually transmitted diseases remains a cause for concern . Not only does this increase the risk of HIV infection, it also shows that the acceptance of condoms is declining and the preventive measures of the last few decades are obviously losing their effectiveness.

Austria

At the beginning of 2008, around 12,000 to 15,000 people were living with HIV in Austria, around half of them in Vienna . The number of new infections has been around 450 per year since 2003 (2015: 428 ^[91] ). The lowest rate was in 1997 with 297, the highest in 1993 with 561 new infections. The number of new infections has now remained relatively constant. Between 1983 and May 5, 2008, 2,608 people contracted AIDS in Austria and 1,468 died. From 2003, with 50 new cases, they rose to 65 in 2004.

In 2006, almost 42% of new infections were through heterosexual contacts (1998 it was 27%), 28.6% through homosexual contacts and 20.5% through injecting drug use.

Around one million HIV antibody tests are carried out in Austria every year (of which 500,000 are financed by donations). One problem is that the tests are often carried out in the wrong target group (pensioners). On the one hand, a lot is tested, on the other hand, many of those affected only become aware of the HIV infection in the course of the actual illness.

Switzerland

In Switzerland, 519 positive HIV tests were reported in 2014. Since 2008 there has been a continuous, slightly decreasing trend in the number of HIV diagnoses. The cantons of Zurich , Vaud and Geneva are particularly badly affected .

In 2014, 50% of infections occurred in men who have sex with men. The number of infections after heterosexual intercourse follows with 39.1%. Infections after drug use are falling continuously and are at 1.6%.

In men (both homosexual and straight) HIV infection occurred more often through casual sex than through sex with a steady partner. On the other hand, women were mainly infected in a stable partnership. Accordingly, a stable partnership does not necessarily protect against HIV. ^[92]

Africa

The HIV/AIDS pandemic is at its worst in sub- Saharan Africa . 24.7 million people live here with an HIV infection (about one in twenty adults is infected). The main routes of transmission of HIV differ fundamentally from those in Europe and North America: Heterosexual sexual intercourse is by far the most common route of transmission in Africa, accounting for around 50% of HIV infections. A further 5 to 10% of infections occur through infected blood transfusions. Transmission of the virus from HIV-positive pregnant women to their newborns during pregnancy, childbirth and breastfeeding is another route of transmission. In some countries, the life expectancy had increased due to the immunodeficiency diseasereduced by more than ten years. In the meantime the situation has improved. In 2013, about half of those infected in sub-Saharan Africa knew their HIV status. Of these, 87% received antiretroviral therapy. ^[93]

There seem to be a number of factors that favor the spread of the HI virus: while in Europe and North America, shortly after the discovery of the HI virus, the mass media informed large parts of the population with information campaigns about the deadly dangers of HIV infection and prevention, AIDS remained a taboo subject in many parts of Africa. This gave the HI virus almost twenty years more time to spread unhindered.

successor states of the Soviet Union

The first HIV infections in the Soviet Union were not registered until the late 1980s. An epidemic spread began in the early 1990s, initially almost exclusively among injectable drug users. The main route of infection was the sharing of needles. As drug addiction spread after the collapse of the Soviet Union, the number of HIV infections also increased.

To this day, where up to 60% of new infections occur sexually, depending on the region, their emergence in the drug milieu shapes the appearance of the HIV epidemic in the successor states of the Soviet Union. Ukraine was the hardest hit and in terms of the characteristics of the epidemic it is exemplary for many regions of the former Soviet Union .

According to information provided at the beginning of the World AIDS Conference in 2018, new infections in Eastern Europe and Central Asia were the only regions in the world to increase between 2010 and 2016, with 80 percent of this affecting Russia , ^[94] where the number of new infections in 2017 was twice as high as according to UNAIDS 2005. ^[95] In 2019, the consumer protection authority there counted just over a million people infected and around 80 new infections every day, according to Vadim Pokrovsky. ^[96]

story

origin theories

The simian immunodeficiency virus (SIV) found in monkey species is almost identical to the human HI virus . It may have existed for at least 32,000 to 75,000 years, based on comparisons of samples taken from Bioko Island in the Gulf of Guinea off Africa and mainland Africa. ^[97] A major distinction is made between the African SIVcpz (from chimpanzee ), from which HIV-1 descends, and the Asian SIVmac (from macaque ), from which the rarer HIV-2 descends.

Genetic analyzes by virologists at the University of Alabama at Birmingham in 2003 show that SIVcpz is a combination of two viral strains found in monkeys and collared mangabeys . Because these species of chimpanzees are hunted and eaten, the chimpanzees could have become infected with the two strains of the virus, which could then have formed the SI virus in their bodies. ^[98]

According to the researchers, the transmission of this SI virus to humans probably took place before the 1930s through injuries sustained when hunting or eating chimpanzees, although there are indications that this occurred in isolated cases earlier. Further scientific investigations showed that the HI virus first appeared in West Africa, but it has not been clarified with absolute certainty whether there were not several virus foci. Recent phylogenetic studies, i.e. comparisons of relationships between the different subtypes of HIV and between HIV and SIV, suggest that several independent transmissions from chimpanzees to humans took place in Cameroon and/or its neighboring countries.

The oldest blood sample known to contain HIV antibodies was taken from an adult male in Congo in 1959. However, the authenticity of this sample has not been clarified with certainty. ^[99] HIV genes were found in old paraffin DNA samples from a woman who died in the Congo (1960, lymph node tissue), an American youth (1969) and a Norwegian sailor (1976).

conspiracy theory

In addition to the currently accepted theory, the KGB , as part of the “ Infection ” disinformation campaign directed against the United States, spread the claim that a novel virus had been discovered by US researchers looking for suitable agents for biological warfare in Africa at the US military laboratory Fort Detrick multiplied and examined, and finally escaped in the process. ^[100]

A scientifically supported hypothesis of an artificial origin of HIV was then developed by Jakob Segal from 1985 onwards .

First infections

The earliest documented infection with HIV-1 was found in blood samples taken in 1959 from a man in Léopoldville ( Belgian Congo ). Comparison with later samples from a Norwegian seaman's family who died of AIDS in 1976 suggests divergence from a common ancestor from the 1940s to early 1950s. It is believed that HIV-1 jumped to humans a few years earlier. However, the genetic difference between HIV-1 and HIV-2 also suggests that these subtypes diverged much earlier. ^[101] Geneticist Bette Korber of Los Alamos National Laboratoryin 2000, using the 1959 sample, dated the first transmission to around 1931. Evolutionary biologist Michael Worobey of the University of Arizona , in 2008, using an additional 1960 sample, dated the first transmission to between 1884 and 1924 He surmises that the establishment of the colonial cities helped the virus gain a foothold. ^[102]

First descriptions of the disease

In 1981, Michael S. Gottlieb described an accumulation of a rare form of pneumonia in the June 5 issue of the Morbidity and Mortality Weekly Report . This form, caused by the fungus Pneumocystis jirovecii , almost exclusively affects patients with severe immunodeficiency, but Gottlieb found it in five previously healthy homosexual men in Los Angeles. ^[103] Similar reports from other US cities followed. In addition, other opportunistic diseases - such as Kaposi's sarcoma - have also increased – found to predominantly affect patients with a weakened immune system. ^[104]

Early on, acquired immunodeficiency disease, which can be sexually transmitted, was considered a likely cause. Initially there was no official name, and references were often made to the names of the diseases, such as lymphadenopathy or Kaposi's sarcoma , sometimes with a reference to homosexual men; ^{[105] [106]} the CDC task force was named Kaposi's Sarcoma and Opportunistic Infections , which was also used for reports. ^{[107] [108]} In the general press, from May 1982 onwards, Gay Related Immune Deficiency (GRID) ^[109] orGay People's Immuno Deficiency Syndrome (GIDS). However, further epidemiological studies in the USA showed that the disease also occurred among hemophiliacs , ^[110] recipients of blood (e.g. through blood transfusions ) ^[111] and heterosexual drug users, suggesting parenteral transmission in addition to sexual transmission. In search of a name, the CDC also created the name "the 4H disease", referring to the supposed main affected groups: Haitians , homosexuals , haemophiles and heroin addicts . ^[112]On July 27, 1982, a conference agreed on the descriptive name Acquired Immune Deficiency Syndrome and the abbreviation AIDS, ^[113] which was used from August 1982 ^[2] and from September 1982 at the CDC ^[114] and in French language area as “Syndrome d'Immuno-Déficience Acquise” (SIDA).

In West Germany, Der Spiegel was first reported on May 31, 1982 under the title Der Schreck von drüben , ^[115] and the disease was first diagnosed in July 1982 in a patient from Frankfurt am Main. ^[116] In Austria, the first two cases were reported in April 1983, and the Austrian daily newspapers reported for the first time in the spring of 1983 on the occasion of the first death. Many media reported in lurid tones; Der Spiegel characterized the disease as “homosexual plague” or “gay plague”. ^{[117] [118]} As a result, the HOSI Vienna created with Klaus Wolffand Christian Kunz published an information leaflet aimed at gay men and published it together with the "Vienna Working Group for Public Health". It was the first AIDS information booklet in Europe. ^[119]

Isolation of the virus and first therapies

In 1983, a French research group led by Françoise Barré-Sinoussi and Luc Montagnier isolated a previously unknown retrovirus , lymphadenopathy virus (LAV), which they suspected to be the cause of AIDS. ^[120] A causal relationship between the virus and the immunodeficiency disease was claimed shortly thereafter. In 1984, a virus discovered in AIDS patients was named Human T-cell Lymphotropic Virus-III (HTLV-III) at the US Cancer Institute. ^[121] In March 1985 further reports on LAV and HTLV-III revealed that they are identical. In 1985, Robert Gallo receivedthe US patent for the first ELISA antibody test to receive US regulatory approval. In 1986, the name human immunodeficiency virus (HIV) ^[122] was established for the virus. A year later, in 1987, the first therapeutic agent, AZT (Retrovir), was approved. In 1989, pentamidine inhalation was introduced in HIV patients to prevent Pneumocystis pneumonia.

In January 1982, Gay Men's Health Crisis (GMHC) was founded as the oldest organization to support people living with AIDS in New York City . In 1983 the AIDS-Hilfe was founded in Berlin, followed in 1985 in Vienna and the Swiss AIDS-Hilfe . In the same year, the first world AIDS conference took place in Atlanta (USA) , and with Rock Hudson the first world star died as a result of immunodeficiency. In March 1987, the activist political initiative Act Up split off from the GMHC .

When a question about AIDS was raised at a routine White House press conference on October 15, 1982, the subject was ridiculed. ^[123] The then US President Ronald Reagan found official words for the first time in May 1987 at the 3rd International AIDS Conference in Washington. Elizabeth Taylor had previously written him a pleading letter to help break the archaic stigma ("gay disease"). By then, 36,058 US citizens had been diagnosed, 20,849 had died as a result, and the infection had been detected in 113 countries. ^[124]

In 1985, Norman L. Letvin established the first non-human primate model for research into HIV after he was able to isolate the simian immunodeficiency virus (SIV) and demonstrate that it causes AIDS-like damage to the immune system and immune system in Indian rhesus monkeys caused deaths. ^[125]

The WHO Global Program on HIV/AIDS has been active since 1987 , from which UNAIDS emerged in 1996. In 1988, the WHO declared December 1st as World AIDS Day . In 2000, subsequent US President Bill Clinton declared AIDS an "enemy of the state" because the epidemic could topple governments, wreak havoc on the global economy and trigger ethnic conflicts. ^[124]

social development

In the beginning, the disease was perceived by the public as a problem for “fringe groups” such as homosexuals and drug addicts. However, this changed dramatically with the advent of HIV testing. Because even people without clinical symptoms had antibodies, which indicated a symptom-free latency period of several years, during which the virus might also have been passed on. In 1984, research found that AIDS in Kinshasa was equally prevalent in men and women, regardless of drug use and blood transfusions.

In the USA it was reported in 1985 that in examined hemophiliacs ("hemophiliacs") who had been infected through stored blood, the infection rate of the wives was 70%. The realization that the risk of infection from heterosexual intercourse appeared to be significantly higher than initially assumed led to great public interest. The combination of the now known routes of infection and the long latency period gave epidemiological projections a pessimistic picture.

In 1985, the activist and director Rosa von Praunheim organized the first major AIDS benefit in Germany, in Berlin's Tempodrom , and won well-known artists such as Herbert Grönemeyer , André Heller and Wolf Biermann for it . Von Praunheim made A Virus knows no Moral , the first German film about AIDS, and publicly campaigned for education and safer sex. ^[126] In 1987 the Federal Office for Health Education launched a large-scale media education campaign in the Federal Republic of Germany with the slogan Don't give AIDS a chance . The best known was a commercial from 1989Hella von Sinnen , who also acted as nurse Rita in A virus knows no morality , as a cashier who shouted loudly across the store: "Tina, how much do the condoms cost?" when the customer, played by Ingolf Lück , wanted to buy them. ^[127]

The annual doubling of new cases in the Federal Republic only lasted from 1984 to 1987, after which the increase in the number of cases was less steep until the numbers leveled off at around 2000 in 1993. As a result, public interest in HIV/AIDS quickly changed again. In 2015, around 2.1 million people were newly infected with the virus worldwide, and around 1.1 million people died from it in the same year. ^[77]

Red ribbon becomes symbol for fight against AIDS

In 1990, the Red Ribbon was established at the San Francisco AIDS Conference to protest discrimination against HIV-infected people. A year later, the red ribbon became an international symbol for the fight against AIDS. In 1992, the World AIDS Congress was moved from Boston to Amsterdam due to US entry requirements. In addition, the Mercury Phoenix Trust was established by the remaining Queen members in memory of Freddie Mercury .

Changes after the introduction of the PCR test for HIV

In 1994, the HIV- PCR was established as an important diagnostic test for therapy control of the course of infection. The following year, 1995, the first HIV protease inhibitor, saquinavir, was commercialized in the United States. The following year, nevirapine became the first non-nucleoside reverse transcriptase inhibitor to be approved. Due to the intensive combination therapy, the death rate in the USA fell drastically in 1997. In 2003, enfuvirtide (Fuzeon) was the first fusion inhibitor approved in the United States. In 2004 the WHO started the 3 by 5 initiative: In 2005 three million infected people were to be supplied with medication.

Different theses

Despite solid scientific evidence, a very small number of scientists dispute either the existence of HIV or the link between HIV and AIDS. These include in particular the German-American retrovirologist Peter Duesberg ^[128] and the chemist Kary Mullis . Her theses influenced former President of South Africa , Thabo Mbeki , who appointed Duesberg as a member of the South African AIDS Advisory Commission in 2001. ^[129] In South Africa, about 15.3% of the population had HIV/AIDS in 2001, and about 200,000 people died of AIDS there that same year. ^[4] Kary Mullis is pro-discovery of PCR-procedure, for which he received the Nobel Prize in Chemistry and with which, among other things, HI viruses are detected in the body of those affected. However, he himself has never done any research on HIV or AIDS. ^[130] However, after describing himself as a possible alien abduction victim and declaring his fondness for astrology , his reputation as a scientist has suffered greatly. ^[131]

The position of the AIDS deniers is classified as a dangerous conspiracy theory and sharply criticized by the overwhelming majority of medical professionals and scientists. The Robert Koch Institute also commented on these positions. ^[132] In South Africa , public health policies based on denying the link between HIV and AIDS delayed the introduction of HIV therapy until 2004. It is believed that as a result of these policies, between 2000 and 2005, there were at least premature deaths from AIDS 330,000 people came and that 35,000 newborns were infected with HIV due to a lack of HIV infection prevention. ^{[133] [134] [135] [136] [137]}

Socio-Ethical Assessment

The disease syndrome AIDS has become a serious challenge worldwide for those directly affected, in medicine, science, but also for all those who care for sick people or live with them.

Far from any stigmatization ^[138] of AIDS patients (see: Discrimination against people with HIV/AIDS ), it is important to find ways and means of helping them more effectively: be it through therapeutic measures that are still not sufficiently available , be it in terms of symptomatic therapy ^[139] and palliative medicine . ^[140] Comprehensive and effective prevention is also required .

The search for an ethically justifiable strategy to combat HIV/AIDS sometimes leads to the opposite: some emphasize the absolute necessity of an exclusively or primarily "technical" protection against the spread of the disease. Others see this answer as insufficient or reject it for reasons of religious ethics. They re-emphasize the value of permanent marital fidelity or, in specific cases, call for temporary or complete abstinence . The propagation of condoms as protection against AIDS is questionable from a religious-Christian point of view. It is argued that this is how one becomes with promiscuityand promotes an irresponsible lifestyle associated with certain sexual practices, which exposes oneself and others to mortal danger. However, these demands are to be seen in the context of the moral teachings, which are particularly widespread in the Catholic Church and which rate promiscuity negatively. Since the Catholic Church had considerable social influence during the spread of AIDS in Africa, numerous new infections were accepted as a result of the years of obstruction to education and prevention (e.g. sex education in schools and the distribution of condoms). ^[141] In the interview book Licht der Welt , published in 2010, the head of the Roman Catholic Church, Pope Benedict XVI , emphasized .that he does not see the use of condoms "of course as a real and moral solution". A justified individual case for an exception to this attitude could be that male prostitutes use a condom. This could then be "a first step towards moralization" and help to develop an awareness "that not everything is permitted and you can't do everything you want". In principle, however, the Pope continued to reject the use of condoms in the fight against the global epidemic. ^[142]

People living with HIV and AIDS are often subject to stigma and discrimination. A study by the German AIDS Aid in 2012 came to the conclusion that 77% of the more than 1100 HIV-positive people surveyed had been discriminated against in the year before the survey – from gossip to insults to physical attacks. More positive people lost their jobs because of discrimination than because of health reasons. Dismissals were related to discrimination in 84% of cases. Around 20% of those surveyed had been refused medical treatment (e.g. at the dentist) in the year before the survey because of HIV. ^[143]Apart from open rejection, HIV patients also repeatedly report delayed appointments, separate treatment times or discrimination, e.g. B. with reference to labour-intensive hygiene guidelines. However, the scientific specialist association German AIDS Society (DAIG e. V.) and the German Working Group of Resident Physicians in the Care of HIV-Infected Persons (DAGNÄ) emphasize that in the dental treatment of HIV-infected persons no hygienic requirements that go beyond the standard measures apply or needed to prevent HIV transmission. ^[144]

In Austria in particular, the term “social AIDS” has been retained for the discrimination against HIV-positive people. ^[145] Even doctors who are in principle obliged to treat them refuse treatment in individual cases ("[...] have no desire to expose themselves to such a risk [...]"). ^[146] In Hanau and the Main-Kinzig-Kreis , a survey with telephone contact and questionnaire was started, but with little response. Practice staff did not know what to do with the terms HIV and AIDS. The main reason for a refusal was the alleged higher hygiene requirements in the treatment of people with HIV. It is generally necessary to work hygienically in a practice so that there is no risk of transmission.^[147] About 16% of HIV-positive people in Germany are still unaware of their infection. The AIDS support and other organizationswant to educate the public throughout the yearWorld AIDS Day on December 1st is also used for this purpose, and the Life Ball in Vienna, which has meanwhile gained international recognition, not only wants to collect donations, but also wants to use the media presence to fight against stigmatization with positive slogans.

See also

• List of personalities who died from AIDS

literature

guidelines

• S2k guidelines for antiretroviral therapy for HIV infection from the German AIDS Society (DAIG). In: AWMF online (as of 2014)
• S2k guideline Antiretroviral therapy for HIV infection in children and adolescents of the German AIDS Society (DAIG). In: AWMF online (as of 2019)
• S2 guideline for HIV pre-exposure prophylaxis (PrEP) of the German AIDS Society (DAIG). In: AWMF online (as of 2018)
• S2k guideline Antiretroviral therapy for HIV infection in children and adolescents of the German AIDS Society (DAIG). In: AWMF online (as of 2019)
• S2k guideline HIV therapy in pregnancy and in HIV-exposed newborns of the German AIDS Society (DAIG). In: AWMF online (as of 2020)

magazine

• The scientific journal AIDS Reviews is published quarterly and publishes reviews that deal with various aspects of HIV and AIDS.

Miscellaneous

chronologically

• Peter Lichtenberg, Michael Malm (editor): AIDS: facts and consequences. Interim report of the Enquete Commission of the 11th German Bundestag "Dangers of AIDS and effective ways to contain it". Publisher: German Bundestag, Public Relations Department. Down to business. Themes of Parliamentary Advice, Vol. 3/88. Bonn 1988, ISBN 3-924521-22-0 (283 pages).
• Birgit Adam : The punishment of Venus. A cultural history of venereal diseases. Orbis, Munich 2001, ISBN 3-572-01268-6 , here: pp. 23-25 ​​(HIV infection/AIDS) and 205-233 (AIDS - the lust epidemic of today?)
• Hansjoerg Dilger: Life with AIDS. Illness, Death, and Social Relations in Africa . An ethnography. Campus, Frankfurt am Main 2005, ISBN 3-593-37716-0 .
• Bärbel Häcker: AIDS. In: Werner E. Gerabek , Bernhard D. Haage, Gundolf Keil , Wolfgang Wegner (eds.): Encyclopedia of Medical History. De Gruyter, Berlin/ New York 2005, ISBN 3-11-015714-4 , pp. 20–22.
• Allan Stratton: What nobody talks about. Novel. Deutscher Taschenbuch Verlag, Munich 2005, ISBN 3-423-78204-8 .
• Bartholomäus Grill, Stefan Hippler: God, AIDS, Africa. The Deadly Silence of the Catholic Church . With a foreword by Henning Mankell. Bastei Lübbe, Bergisch Gladbach 2009, ISBN 978-3-404-60615-3
• James Chin: The AIDS Myth. Medical facts versus political correctness. Translated by Catherine Hornung. Ares Verlag , Graz 2009, ISBN 3-902475-50-1 .
• Susanne Roeßiger: Safer Sex and Solidarity. The collection of international AIDS posters in the German Hygiene Museum. In: Zeithistorische Forschungen / Studies in Contemporary History 10 (2013), pp. 502-514.
• Henning Tümmers: "Don't give AIDS a chance". A prevention message in two German states. In: Zeithistorische Forschungen / Studies in Contemporary History 10 (2013), pp. 491-501.
• Henning Tummers: AIDS. Autopsy of a threat in divided Germany. Wallstein Verlag, Goettingen 2017, ISBN 978-3-8353-3005-4 .
• W. David Hardy: Fundamentals of HIV Medicine 2019. Oxford 2019, [email protected] (English).

web links

• German AIDS Aid
• German AIDS Foundation
• Austrian AIDS Aid
• AIDS Education Switzerland Information material for download
• AIDS-Hilfe Schweiz (many brochures can be downloaded)
• UNAIDS – United Nations Joint Program on HIV/AIDS (English, French, Russian, Spanish)
• German working group of established physicians in the care of HIV-infected people (DAGNÄ e. V.) - Information, current developments and list of established HIV specialist practices
• www.hivbuch.de – Detailed and up-to-date information on the subject of HIV and AIDS
• HIV/AIDS: key data and trends for Germany and the federal states. In: rki.de.
• Johannes Georg Gostomzyk: Acquired Immune Deficiency Syndrome (AIDS). In: Historical Encyclopedia of Bavaria . May 28, 2013.
• Sine Maier-Bode, Hildegard Kriwet: Aids. In: planet-wissen.de . ARD

itemizations