The immune cells targeted by the human immunodeficiency virus are

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. Martin Hildebrandt Prof. Bernd Jansen Dr. Ruth Offergeld Prof. Georg Pauli Dr. Uwe Schlenkrich Dr. Volkmar Schottstedt Prof. Rainer Seitz Dr. Johanna Strobel Dr. Hannelore Willkommen. References 1. Luciw PA. Human immunodeficiency viruses and their replication. In: Fields BN, editor. Philadelphia: Lippincott-Raven; Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes.

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Analysis of HIV-1 load in blood, semen and saliva: evidence for different viral compartments in a cross-sectional and longitudinal study. A decisive point is a place, event, system or function that gives an advantage when acquired by a military commander.

The mice also had elevated levels of superoxide radicals, but these effects could be remedied by administering recombinant human ACE2 rhACE2 to the mice, suppressing angiotensin II pathology. However, Wang et al determined the spike protein is capable of binding CD, a glycoprotein often related to tumor development, for entry into the cell Figure 2.

Comparative overview of viral entry and receptor downregulation. Once inside a cell, HIV uses a number of mechanisms to promote transmission of virions to other cells.

The extent of MHC class I downregulation is linked to the progression of AIDS and is thus hypothesized to be primarily for evasion of immune surveillance. The Elastic Defense was a layered defensive tactic used by the Germans in World War II that allowed them to minimize casualties when faced with overwhelming forces.

The modern equivalent is the Resilient Defense that builds upon the same pillars. These strategies utilize mobile forces and importantly connected defensive positions with artillery to repel attacking armies. In our scenario, artillery fire is replaced by cytokines and antibodies released into the system, and our troops are white blood cells fighting on fronts as they change, connected by the bloodstream in a similar fashion to the German defenses being connected by tunnels.

A puzzling report from China reported one patient developed symptoms on January 23rd and was admitted to a hospital on February 6th after chest computed tomography CT confirmed pneumonia. This interaction was confirmed via cryo-electron microscopy and both NspS and NspS complexes were observed. One study described four infants under twenty-eight days old who all had mild symptoms and one of the four was asymptomatic.

This is followed by recruitment of additional immune cells to the site of pyroptosis. This is further complicated as the early stages of HIV infection may go largely unnoticed, often being dismissed as a cold or flu. A research group following a cohort based in San Diego, California identified the most common symptoms of acute HIV infection as fever, myalgia, fatigue, headache, night sweats, pharyngitis, and gastrointestinal symptoms; whereas rash, weight loss, and arthralgia are less common, but prevalent nonetheless.

However, HIV has evolved a mechanism of escape from these proteins. As the viremia in the host begins to decline 1 to 2 weeks after reaching peak levels, the T cell response will spike.

This occurs because the host adaptive immunity takes approximately 21 days to respond to the initial inoculation of HIV. As this occurs, viremia in the host begins to decline and the host will enter the next stage of infection.

As the population of HIV declines, mutant strains are selected for and are able to escape the immune system. The first mutants will have changes in epitopes targeted by T cells, namely env and nef. As selection continues to occur, first by T cells and later by HIV-specific antibodies, HIV will begin to develop clusters of mutations throughout its genome as one of the mechanisms to escape the host immune system.

Though most of the initial strain of HIV will be gone, the few remaining will be mutant strains that are able to efficiently evade the immune system. This may allow them to defeat one threat, and then focus their remaining forces on the other threat. Therefore, although HIV infections may be considered a chronic, epidemic disease, PLWH still live with a virus waiting for an opportunity to attack.

Arbidol, generic name umifenovir, is an anti-influenza medication not currently approved in the US There were no significant differences in the rates of viral clearance for any of the groups, with each group averaging approximately 9 days for patients to test negative for SARS-CoV-2 nucleic acid.

Additionally, While not significant, the remdesivir group had a lower mortality rate than the control group, with Kaplan-Meier estimates of 7.

In this comparative review, we describe the clinical observations derived from small and large cohorts of patients co-infected with HIV and SARS-CoV-2 in several countries, as well as virological similarities and differences between these two pandemic viruses. With HIV known to deplete immune cells in the host, and successful antiretroviral therapy known to rescue immune competency, chronic HIV-infected individuals still face co-morbidities that can sometimes be life-threatening, like severe pulmonary vascular disease.

Current reports in the literature document a wide spectrum of symptoms and severities for COVID, and future research focusing on co-morbidities may elucidate the key factors that determine severity. In stark contrast, SARS-CoV-2 while it causes some lymphopenia, it has the capacity to cause friendly fire with the body, invoking severe cytokine storms that end up hurting the host, with varying degrees of COVID onset, development, and recovery.

Severe COVID has been postulated to result from damaging, elevated immune responses leading to multi-organ failure. Severity of symptoms in this case would vary depending on the individual and the progression of the viral infection. This is illustrated in Figure 3.

This may be due to chronic impact of HIV in lowering the overall immunocompetency of the patients, even when receiving antiretroviral therapy. While immunosuppression would make them more susceptible to infection, it also may decrease the immune response to infection, reducing the damage that occurs from the inflammation resulting from SARS-CoV-2 infection.

While the patients are not immunodeficient, they are immunosuppressed. In turn this would mean a weakened cytokine storm would occur when the virus has reached the lungs and entered the blood, spreading to other organs. The weakened cytokine storm would entail lower systemic inflammation and cause less damage to other organs. Based on the clinical profiles discussed above, the immune system largely determines the progression of COVID symptoms and severity of symptoms.

Following airborne exposure, effective barriers and deployment of the immune system troops can prevent spreading of the SARS-CoV-2 infection to the lower respiratory tract and eventual systemic infection.

If the virus remains in the upper respiratory tract, the yellow box in Figure 3 , only milder symptoms such as anosmia can occur. The novelty of SARS-CoV-2, along with the unknowns associated with the impact of pathogen co-infections, challenges the design of therapeutic approaches that might help patients with increased susceptibility for severe COVID illness. For COVID, an ideal strategy would block viral entry to susceptible cells, disrupt viral replication in cells, and boost the immune system while avoiding an increased release of cytokines on top of the cytokine storm.

Nevertheless, the most important defensive measure to take is still prevention of transmission. The fact that enveloped viruses like SARS-CoV-2 are susceptible to detergents and alcohols make it an easily killable target; therefore, basic hand washing and use of face coverings to contain secretions should prevail as first lines of defense.

The authors report no other conflicts of interest in this work. National Center for Biotechnology Information , U. Published online Mar Author information Article notes Copyright and License information Disclaimer. Received Jan 1; Accepted Feb This work is published and licensed by Dove Medical Press Limited.

By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4. Open in a separate window. Figure 1. Viral Transmission: Deployment SARS-CoV-2 is a respiratory virus, primarily spread from person to person through respiratory droplets containing viral particles.

Key Receptors: Decisive Point A decisive point is a place, event, system or function that gives an advantage when acquired by a military commander.

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