In addition, HIV infections were observed in about 9. The trends in the three main groups affected in Germany proceeded differently: the first peak of infections occurred simultaneously in the groups of MSM and IVD in the mids. In the following years up to the beginning of the s, the number of new HIV infections decreased significantly in both groups. This trend continued in the group of IVD up to with a largely constant low level of new infections since Also in the group of MSM significantly fewer infections occurred during the s.
However, in the period between and a significant increase in HIV infections in MSM was observed and reached a considerably higher plateau in The number of those infected via heterosexual contacts hetero-domestic in Germany has been rising significantly slower in the course of the epidemic than in the MSM and IVD groups. Since the number of new infections in heterosexually infected persons has remained on a constant level.
Autonomous heterosexual infection chains have a minor impact on the spread of the HIV epidemic in Germany. Considering the number of reported new infections, large regional differences can be observed. Especially in densely populated urban areas among others Rhine-Ruhr, Rhine-Main and major cities, the incidence of new diagnoses is much higher than in the remaining regions.
In , the ratio of men to women in the group of new infections was 3. Since the percentage of newly diagnosed cases has been rather stable. In Eastern Europe i. Newly diagnosed HIV infections and modes of transmission in different European countries in www. The molecular epidemiologic data show that HIV-1 group M subtypes have different regional prevalence patterns.
The prevalence of HIV-1 subtypes and HIV-2 in European countries reflects the historic connection of these countries to the corresponding endemic regions in Africa [ 12 , 17 , 93 ]. Africa is the continent that is affected most by HIV infections. The estimated HIV prevalence in Africa varies widely and lies between 0.
Heterosexual contacts are the main route of infection in Africa, and sex work and sexual violence contribute significantly to the spread of the disease. Approximately one third of those infected with HIV received antiretroviral therapy in [ 89 ]. In Asia, about 1. The epidemic is concentrated in distinct groups with a high risk of exposure, such as MSM, sex workers, drug users and transsexuals [ 89 ].
This is a further indication for the continuous evolution of HIV-1 group M in humans. The main mode of transmission is sexual contact among men [ ].
At the beginning of the epidemic the prevalent subtype B strain had a defect in Nef and a lower pathogenicity [ ]. Approximately 1. The main route of transmission is sexual contact between men. About one third of all persons infected with HIV receive antiretroviral therapy [ ]. In Canada, 2, new HIV infections were reported in , the lowest number determined since introduction of the reporting system in In Canada also, MSM represent the mainly affected group.
In Latin America, approximately 1. Further recombinants are found in Brazil and in neighbouring countries [ 16 ]. A general distinction can be made between two principles of detection: antibody and virus detection. HIV antibody screening tests are used for the primary diagnosis followed by a confirmation test in the case of a reactive result in the screening assay. In addition to the ELISA enzyme linked immunosorbent assay or variants of this test system, particle agglutination tests are used.
Depending on the manufacturer, additional antigens derived from the reverse transcriptase and the p24 protein are included in the test systems [ 11 , , , ].
Depending on the immune response and the antibody titre, an infection can be detected serologically after 3 weeks but usually after weeks [ ]. In rare cases, HIV-infected individuals with complete immunosuppression might be HIV antibody-negative, but they have HIV-typical clinical symptoms and measurable virus titres in the blood [ ].
Because ELISAs were developed also for the detection of low antibody levels with the highest sensitivity, false-positive results occur, especially when immune complexes are present in the serum, e.
Furthermore, false-positive results were reported for individuals with autoimmune diseases or allergies and for pregnant women. Mistakes in pre-test conditioning can lead to false-positive screening tests, e. Since the information about a positive HIV finding has far-reaching consequences for the infected individual, it is recommended in cases of a positive result in the initial analysis to test a second, independently taken blood sample.
In the same sample the amount of viral genomes viral load should also be determined using NAT in order to identify the need for antiviral treatment [ , ]. Virus isolation in cell culture takes approximately 6 weeks and is often unsuccessful and costly. For diagnostics in blood establishments virus isolation is of no relevance. The p24 protein forms the inner capsid.
Each virus particle contains approximately 2, p24 molecules [ ]. Detection of p24 antigen is performed using a combination of polyclonal or monoclonal antibodies, following the principle of the sandwich ELISA technique. In the course of the infection, free or particle-bound p24 can be found in plasma.
In some AIDS patients, high levels of p24 antigen can be observed. There is no direct correlation between the number of HIV particles determined by NAT and the p24 antigen concentration in plasma, because p24 is shed from infected cells without associated viral nucleic acid. A positive p24 antigen test result must also be confirmed. Most of the HIV-1 p24 antigen tests react also with the HIV-2 p25 antigen, but in some systems with reduced sensitivity.
Screening of blood donations for p24 protein in addition to HIV antibodies is not mandatory in Germany [ ]. For analysis of the viral load and the presence of HIV in blood donations, RNA is extracted from virus particles in plasma.
Genome detection can be done either via direct amplification of defined target sequences or through the use of probes with subsequent signal amplification.
One genome equivalent ge equals 1. In plasma pools, virus particles can be concentrated, e. For quality control and quantification, standard materials are available [ , , ]. NAT systems have been developed and made commercially available that use primers binding preferentially and stringently to the genome of HIV-1 M:B; therefore, with a few exceptions, viruses of the type HIV-1 M:B are detected with the highest sensitivity.
Depending on the test design and the target sequence, e. Taking into account the genetic variability of the HIV genome, it is advantageous and therefore has become compulsory for Germany in to use so-called dual-target amplification techniques, i.
At present, only tests from a few manufacturers are used in Germany for the screening of blood donations with commercial NAT tests. However, since several blood establishments and manufacturers of plasma derivatives have developed their own HIV amplification assays, so-called homemade or in-house assays [ , , ].
In case a test system is sufficiently sensitive, e. In order to avoid contamination of the NAT assays, fully automated processing systems have been established [ ]. For quantitative HIV-2 genome detection, commercial tests have become available in [ 38 ].
For quality control and quantification, an international standard for HIV-2 has been developed [ ]. In Germany, every year approximately 7. The HIV prevalence among new donors has been largely stable since 6. However, an upward trend of seroconversions was observed in repeat donors from 2. This increase is almost entirely due to an increase in HIV infection among male repeat donors.
Most of these donors have both a reactive antibody test and a positive NAT. Almost in all cases there was a sexual exposure; nearly half of the infected men indicated sexual contacts with men as the most likely route of infection. Almost all of the HIV-positive donors MSM and heterosexuals would have been deferred from blood donation on the base of their risk of exposure.
In previous years, it was noticed that a significantly higher proportion of HIV-infected persons was found in the population of plasma donors compared to whole blood donors. This difference is becoming increasingly larger in the population of repeat donors. Whereas the HIV incidence in the group of repeat whole blood donors increased between and from 1.
The reasons for this increase are unclear. The site of plasma donation centres in cities may play a role as well as the higher proportion of young male plasma donors. The trend described for Germany is not observed in other countries [ ]. Criteria are defined for the permanent or temporary deferral from donation with respect to the transmission of HIV. Permanently deferred from donation are the following:.
From a scientific perspective it appears to be justified to implement a temporary deferral for those persons with a high-risk sexual behaviour that they have verifiably changed.
There is currently an intensive discussion on a national and international level whether lifetime deferral of MSM and of sex workers could be replaced by a sufficient temporary deferral, taking into account the last sexual contact between men or in sex work, respectively [ , , ]. Reactive screening test results must be followed by a serologic confirmation test or a NAT assay. An additional second blood sample has to be investigated for confirmation of an HIV infection see 1.
Until the results are clarified, the donation is separated and should be preserved for additional investigations. The donor is deferred until the final results are available [ ].
According to current knowledge, the vast majority of reactive HIV antibody screening test results of blood donors are non-specific, i. The diagnostic window period, which is between 3 and 6 weeks for antibody screening tests, can be shortened by application of NAT.
Depending on the level of viraemia, the sensitivity of the assay used and the infecting HIV, an infection can be detected as early as about 11 days post infection see also 1. Reference materials for the detection of different HIV-1 genotypes are available [ ]. Despite the high labour input and costs, screening with NAT is justifiable, because the majority of potential HIV transmissions by cellular blood components have been prevented through NAT in recent years [ , , , , , , ].
In view of the high costs of NAT and the currently low incidence in blood donors, the financial investment for the elimination of infectious, but still HIV antibody-negative donations is high, but justified. The costs are estimated to be about EUR 7. In several cases, NAT tests containing only primers directed against only one genome region were not able to detect HIV with mutations in the target region of the primers. To increase safety, it has been made mandatory to use at least two different target regions for donor screening dual target NAT [ , ].
Sequence analysis of several genome regions can be used to clarify reliably an etiologic relationship of an HIV transmission by the donation [ , , ]. According to the haemotherapy guidelines, the state of health and pre-existing relevant diseases have to be assessed by using a donor history questionnaire and a confidential interview. This can help to identify and defer persons whose donation could represent a health risk to themselves or could be associated with the risk of transmitting a disease to others.
For further queries and explanations a physician has to be available. The medical history should cover all issues of the donor selection criteria exclusion criteria of the haemotherapy guidelines. These constitute a legally binding basis for decision-making in selecting donors. Since an updated standardised donor history questionnaire is available www. Perinatally HIV-infected children who since birth have been effectively treated with antiviral drugs for years may be antibody-negative due to early suppression of HIV replication and could theoretically become potential blood donors.
Recommendations on how to inform a donor with positive HIV test results are given in the vote on look-back procedures of the Arbeitskreis Blut [ ].
HIV-infected donors should be informed in person and in writing by the blood establishment. HIV-infected donors should be counselled and referred to a general practitioner or a specialised centre for further care. The counselling should include information about the HIV transmission routes and the possibility of antiretroviral therapy [ , ] see also 3. The information given should also include the fact that they are no longer suitable as a blood, plasma or organ donor in Germany.
In South Africa, the possibility of exceptions in cases of kidney transplantation to HIV-infected recipients is suggested [ ]. Clarification of the possible origin of the donor's infection is of epidemiologic interest. Efforts should be made in the donor interview to identify the route and the cause of infection, especially in order to prevent further transmission of the HIV infection. A template provided by the Robert Koch Institute with a standardized questionnaire simplifies clarification and supports a nationwide standardised registration system of HIV transmission modes in the donor population.
Prior to the introduction of compulsory testing for HIV antibodies in May and October , about 1, haemophiliacs and about transfusion recipients were infected in Germany with HIV by blood donations and plasma derivatives [ ].
With the introduction of antibody screening tests and obligatory virus inactivation procedures in the production process of plasma derivatives, the number of HIV and hepatitis virus infections by transfusion declined significantly, especially in the first 2 years. According to reports to the Paul Ehrlich Institute, 2 HIV transmissions by cellular blood components red blood cell concentrates have occurred after the introduction of NAT screening in [ ].
Both transmissions were due to very recent infections and a failure of the NAT systems used. In the case of , presumably a low viral load and mutations in the primer binding region were responsible for the false-negative test results [ ].
Regarding the transmission reported in , the HIV-positive donor sample was repeatedly tested negative with the NAT system used [ ]. The risk of HIV transmission by transfusion is estimated to be very low. Based on the data on donor testing and haemovigilance in the time period between and , a risk of transmission of 1 in 9.
Taking recent risk models that include specified interdonation intervals into the assessment, the remaining residual risk of an undetected infectious whole blood donation is estimated to be As recommended for HIV-infected donors, plasma and lymphocytes of the HIV-infected recipient should also be stored [ ] in order to possibly clarify the origin of infection and the transmission using molecular methods see 2.
There is no protective immunity against HIV. The older a patient is at the time of infection, the higher the risk to develop immunodeficiency at an early stage of infection [ , , ]. Since , attempts were made to develop a vaccine against HIV with high expenditures regarding both personnel and finances. So far all trials have been unsuccessful, although new knowledge was acquired.
Therefore, it will still take many years to develop an effective and preventive vaccine [ , ]. The course of an HIV infection is always chronic, ending fatally without antiretroviral therapy. CD4 cell disintegration and clinical symptoms can be decelerated or suppressed by antiretroviral therapy for decades [ ].
With antiviral therapy it is possible to extend the phase without or with only slight symptoms for many years [ , ]. Further drugs are being developed [ ]. A combination of different active substance groups of antiviral drugs should delay the development of resistant HIV in the patient as long as possible.
So far, the percentage of patients carrying resistant HIV has remained largely stable [ ]. Therefore, a genotypic resistance test should be done prior to treatment in order to avoid a reduced effectiveness of the chosen therapy [ , ]. Overview of the drugs available for HIV therapy — see also [ ].
The decision for treatment should be made by both the specialised physician and the informed patient. The best long-term therapeutic results can be reached when treatment is started before the onset of symptoms of immunodeficiency.
In some cases, particularly in new-borns, it is indicated to start therapy early after the infection is realised, i. Also in the case of an early treatment, it is necessary to determine whether drug-resistant viruses were transmitted [ , , ].
Only some of the drugs are effective against HIV-2 [ ]. Medication with antiviral drugs and the effect of the drugs on viral replication can lead to the recovery of functions of the immune system and consequently to an improvement or disappearance of clinical symptoms. Although a combination of three or four drugs appears to be very successful in suppressing the replication of HIV, highly active antiviral therapy HAART has adverse effects that can severely reduce the quality of life.
Furthermore, antiretroviral drugs interfere partly with each other and sometimes with other medication via the cytochrome P system. Common side-effects include diarrhoea, insomnia, lack of concentration and inability to gain weight despite adequate food intake; also diabetes, anaemia and neurologic disorders are observed [ 5 , 29 ].
A supplementary immunotherapy with interleukins, e. HIV can be transmitted through body fluids such as blood, plasma or serum, genital secretions and transplanted organs such as kidney, bone and cornea; infection by artificial insemination has been documented.
Transmission via saliva and bite injuries has been reported in individual cases; recently a case was reported from China [ ]. Open lesions can be points of entry for HIV [ ]. HIV can neither be transmitted by aerosols, social contacts and stings by insects or arthropods, nor by food or water.
Blood components: Since only 2 HIV transmissions through blood components have been reported in Germany [ ]. There is evidence that immediate initiation of HIV post exposure prophylaxis can prevent an infection after needle stick injury in individual cases [ , , ]. The implementation of donor selection, antibody screening and inactivation procedures has made a transmission of enveloped viruses which are comparable in their structure to HIV no longer possible.
Due to donor selection, testing of donations for HIV antibodies and HIV-1 genome NAT , the probability of blood and blood products to be contaminated with HIV is very low, with an estimated residual risk of below 1 in 1 million see 2. In addition, plasma for fractionation, which is obtained by plasmapheresis, is frequently stored for an inventory hold period of at least 60 days before further processing. If an HIV infection is confirmed in a donor, earlier samples are re-tested in the context of a look-back process, and infectious donations from donors in the seroconversion phase still in stock can be discarded.
This voluntary measure further reduces the theoretical viral load of plasma pools for the production of plasma derivatives. The production and purification of individual proteins from plasma is not sufficient to completely rem ove HIV. Therefore additional validated procedures for an effective depletion and inactivation of viruses must be applied [ ]. No transmissions of HIV by plasma derivatives have been reported since the consistent implementation of effective methods for removing and inactivating viruses in the production process.
Accordingly, the experimentally determined inactivation capacity of the manufacturing process is supported by epidemiologic data. HIV is sensitive to heat and detergents see 1. Heat treatment of lyophilized products e. Because of the heat sensitivity of plasma proteins the inactivation procedures must be carried out under appropriate validated conditions [ ].
The product should optimally maintain its biologic activity and native conformation, while potentially contaminating viruses should be inactivated under the production conditions [ , ].
Further methods for inactivation of HIV and other viruses in blood components have been developed. These are chemical e.
Clinical trials concerning the potency and tolerability of plasma treated with methylene blue, inactivated with SD or treated with amotosalen [ ] and riboflavin [ ] have been performed only to a limited extent [ ].
A further substance to inactivate HIV in whole blood or packed red blood cells is S [ ]. Validation of the various removal and inactivation steps must be carried out following the actual production processes using HIV [ , , ]. HIV can be propagated to sufficient amounts in cell culture, enabling the spiking of the different source materials under laboratory conditions. Individual steps have to be investigated mimicking the different production processes with regard to their virus removal or inactivation capacity by determining the infectious titres at the start and the end of each production step.
The occurrence of HIV in the blood and plasma donors collectives since has been leading to a continuous increase in the viral safety requirements for the production of blood components and plasma derivatives. The initially observed diagnostic window period of days is now reduced to about 11 days due to the introduction of HIV NAT.
No HIV infection with fresh frozen plasma, which is subject to quarantine storage, has become known since Only products with a high safety margin regarding HIV and hepatitis viruses are approved by the authorities.
After detection of circulating HIV strains that were not detected in NAT assays due to mutation or deletion of primer-binding regions, it has become mandatory to use dual-target NAT in order to increase the safety of blood products. However, HIV is genetically variable, and there is a need for continuous research to sustain the achieved level of safety.
Continuous monitoring of circulating viruses is necessary to enable the detection of emerging new variants of HIV as early as possible and to enable accordingly the adaption and improvement of HIV detection test systems. National Center for Biotechnology Information , U. Journal List Transfus Med Hemother v. Transfus Med Hemother. Published online May 9. Author information Article notes Copyright and License information Disclaimer.
Received Jan 13; Accepted Feb Karger GmbH, Freiburg. This article has been cited by other articles in PMC. Open in a separate window. Table 1 Overview of HIV-1 proteins and their function. Table 2 Newly diagnosed HIV infections and modes of transmission in different European countries in www. Confirmatory Test Western blot, Immunoblot Because ELISAs were developed also for the detection of low antibody levels with the highest sensitivity, false-positive results occur, especially when immune complexes are present in the serum, e.
Permanently deferred from donation are the following: — Persons with a confirmed HIV infection. Cost-Benefit Calculation In view of the high costs of NAT and the currently low incidence in blood donors, the financial investment for the elimination of infectious, but still HIV antibody-negative donations is high, but justified. HIV Vaccination Since , attempts were made to develop a vaccine against HIV with high expenditures regarding both personnel and finances.
Table 3 Overview of the drugs available for HIV therapy — see also [ ]. Martin Aepfelbacher Dr. Ursula Bauerfeind PD Dr. Reinhard Burger Prof. Margarethe Heiden Prof.
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