147-415: The subtypes of HIV include two main subtypes, known as HIV type 1 (HIV-1) and HIV type 2 (HIV-2). These subtypes have distinct genetic differences and are associated with different epidemiological patterns and clinical characteristics. HIV-1 exhibits a genetic relation to viruses indigenous to chimpanzees and gorillas that inhabit West Africa , while HIV-2 viruses are affiliated with viruses present in
294-649: A false negative result. However, based upon the HIV prevalence rates at most testing centers within the United States, the negative predictive value of these tests is extremely high, meaning that a negative test result will be correct more than 9,997 times in 10,000 (99.97% of the time). The very high negative predictive value of these tests is why the CDC recommends that a negative test result be considered conclusive evidence that an individual does not have HIV. Of course,
441-493: A long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by gag and rev proteins. The SLIP element ( TTTTTT ) is involved in the frameshift in the gag - pol reading frame required to make functional pol . The term viral tropism refers to
588-460: A 1997 survey found that about 2% of HIV-positive samples were from Group O. Its zoonotic origin is SIVgor, which infects gorillas (rather than the more common source, SIVcpz). The group caused some concern because it could not be detected by early versions of the HIV-1 test kits. More advanced HIV tests have now been developed to detect both Group O and Group N. In 2009, a newly analyzed HIV sequence
735-689: A CD4 count as an AIDS criterion was introduced in 1992; the value of 200 was chosen because it corresponded with a greatly increased likelihood of opportunistic infection. Lower CD4 counts in people with AIDS are indicators that prophylaxis against certain types of opportunistic infections should be instituted. Low CD4 T-cell counts are associated with a variety of conditions, including many viral infections, bacterial infections, parasitic infections, primary immunodeficiency, coccidioidomycosis, burns, trauma, intravenous injections of foreign proteins, malnutrition, over-exercising, pregnancy, normal daily variation, psychological stress, and social isolation. This test
882-535: A cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread". In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to
1029-481: A cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans. The molecular structure of the viral spike has now been determined by X-ray crystallography and cryogenic electron microscopy . These advances in structural biology were made possible due to
1176-705: A condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype . In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood , pre-ejaculate , semen , and vaginal fluids . Non-sexual transmission can occur from an infected mother to her infant during pregnancy , during childbirth by exposure to her blood or vaginal fluid, and through breast milk . Within these bodily fluids, HIV
1323-623: A condition of significant risk to health. When the ELISA test is combined with Western Blot, the rate of false positives is extremely low, and diagnostic accuracy is very high (see below). Modern HIV testing is highly accurate. The evidence regarding the risks and benefits of HIV screening was reviewed in July 2005 by the U.S. Preventive Services Task Force. The authors concluded that: ...the use of repeatedly reactive enzyme immunoassay followed by confirmatory western blot or immunofluorescent assay remains
1470-414: A few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection. Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time. The chance of a false-positive result in a standard two-step testing protocol
1617-526: A group P. Each group is believed to represent an independent transmission of simian immunodeficiency virus (SIV) into humans, excluding subtypes within a specific group. The complete genome sequence of HIV-1 contains a total of 39 open reading frames (ORFs) across all six possible reading frames (RFs), but only a few of them are functional. With 'M' for "major", this is by far the most common type of HIV, with more than 90% of HIV/AIDS cases caused by infection with HIV-1 group M viruses. This major HIV, which
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#17327653010061764-481: A high set-point viral load, the host will live for a shorter amount of time and there is a lower probability that the virus will be transmitted to another individual. HIV has evolved to maximize the number of infections to other hosts, and this tendency for selection to favor intermediate strains shows that HIV undergoes stabilizing selection. The virus has also evolved to become more infectious between hosts. There are three different mechanisms that allow HIV to evolve at
1911-402: A human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120 , and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope. The envelope protein, encoded by
2058-574: A key step in the progression to AIDS. A number of studies with subtype B-infected individuals have determined that between 40 and 50 percent of AIDS patients can harbour viruses of the SI and, it is presumed, the X4 phenotypes. HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to West Africa . The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) may assist
2205-406: A lab using the western blot . ELISA testing alone cannot be used to diagnose HIV, even if the test suggests a high probability that antibody to HIV-1 is present. In the United States, such ELISA results are not reported as "positive" unless confirmed by a western blot. The ELISA antibody tests were developed to provide a high level of confidence that donated blood was not infected with HIV. It
2352-769: A monkey species inhabiting the forests of Littoral West Africa. Phylogenetic analyses show that the virus most closely related to the two strains of HIV-2 which spread considerably in humans (HIV-2 groups A and B) is the SIVsmm found in the sooty mangabeys of the Tai forest , in western Ivory Coast . There are six additional known HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from sooty mangabeys to humans. Groups C and D have been found in two people from Liberia, groups E and F have been discovered in two people from Sierra Leone, and groups G and H have been detected in two people from
2499-613: A more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing. RNA can also be processed to produce mature messenger RNAs (mRNAs). In most cases, this processing involves RNA splicing to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of
2646-422: A number attached to the positive test results. Controversy exists over privacy issues. In developing countries, home-based HIV testing and counseling (HBHTC) is an emerging approach for addressing confidentiality issues. HBHTC allows individuals, couples, and families to learn their HIV status in the convenience and privacy of their home environment. Rapid HIV tests are most often used, so results are available for
2793-447: A number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4 T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4 T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to
2940-512: A number. CRF12_BF, for example, is a recombination between subtypes B and F. The spatial movement of these subtypes moved along the railways and waterways of the DRC from Kinshasa to these other areas. These subtypes are sometimes further split into sub-subtypes such as A1 and A2 or F1 and F2. In 2015, the HIV strain CRF19, a recombinant of subtype A, subtype D, and subtype G, with a subtype D protease ,
3087-823: A person is of West African descent or has had sexual contact or shared needles with such a person. West Africa is at the highest risk as it is the origin of the virus. HIV-2 has been found to be less pathogenic than HIV-1. The mechanism of HIV-2 is not clearly defined, nor the difference from HIV-1, however the transmission rate is much lower in HIV-2 than HIV-1. Both viruses can lead to AIDS in infected individuals and both can mutate to develop drug resistance. Disease monitoring in patients with HIV-2 includes clinical evaluation and CD4 cell counts, while treatment includes anti-retroviral therapy (ART), nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PI), and non-nucleoside reverse transcriptase inhibitors (NNRTIs) with
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#17327653010063234-399: A population level. One includes the continuous battle to evolve and overcome the immune system which slows down the evolution of HIV and shifts the virus’ focus towards a population level. Another includes the slow evolution of viral load due to viral load mutations being neutral within the host. The last mechanism focuses on the virus' preference to transmit founding viral strains stored during
3381-561: A positive result when tested in one month; persistently indeterminate results over a period of six months suggests the results are not due to HIV infection. In a generally healthy low-risk population, indeterminate results on western blot occur on the order of 1 in 5,000 patients. However, for those individuals who have had high-risk exposures to individuals where HIV-2 is most prevalent, Western Africa, an inconclusive western blot test may prove infection with HIV-2. The HIV proteins used in western blotting can be produced by recombinant DNA in
3528-488: A probe bound to an enzyme. The amount of virus in the sample can be quantified with sufficient accuracy to detect threefold changes. In the Quantiplex bDNA or branched DNA test, plasma is placed in a centrifuge to concentrate the virus, which is then opened to release its RNA. Special oligonucleotides that bind to viral RNA and to certain oligonucleotides bound to the wall of the vessel are added. In this way, viral RNA
3675-464: A strain of SIV found in sooty mangabees. Since HIV-1 is derived from SIVcpz, and HIV-2 from SIVsm, the genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsm. Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion
3822-558: A target T cell via a virological synapse . Secondly, an antigen-presenting cell (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions in trans (in the case of dendritic cells). Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread. A number of factors contribute to this increased efficiency, including polarised virus budding towards
3969-615: A technique called recombinant immunoblot assay (RIBA). Rapid antibody tests are qualitative immunoassays intended for use in point-of-care testing to aid in the diagnosis of HIV infection. These tests should be used in conjunction with the clinical status, history, and risk factors of the person being tested. The positive predictive value of Rapid Antibody Tests in low-risk populations has not been evaluated. These tests should be used in appropriate multi-test algorithms designed for statistical validation of rapid HIV test results. If no antibodies to HIV are detected, this does not mean
4116-635: A western blot test to confirm the positive result. Following a further increase of false positives in NYC DOHMH STD Clinics during the end of 2007 and beginning of 2008, their clinics opted to forgo further oral screenings, and instead reinstituted testing using finger-stick whole blood. Despite the increase in false positives in NYC DOHMH, the CDC still continues to support the use of noninvasive oral fluid specimens due to their popularity in health clinics and convenience of use. The director of
4263-448: Is also known to still cause AIDS. One of the prevailing challenges in the pursuit of effective management of HIV is the virus's pronounced genetic variability and rapid viral evolution . HIV-1 is the most common and most pathogenic strain of the virus. As of 2022, approximately 1.3 million such infections occur annually. Scientists divide HIV-1 into a major group (group M) and two or more minor groups, namely groups N, O and possibly
4410-420: Is also used occasionally to estimate immune system function for people whose CD4 T cells are impaired for reasons other than HIV infection, which include several blood diseases, several genetic disorders, and the side effects of many chemotherapy drugs. In general, the lower the number of T cells the lower the immune system's function will be. Normal CD4 counts are between 500 and 1500 CD4+ T cells/microliter, and
4557-460: Is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit. The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi apparatus where it is cleaved by furin resulting in
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4704-516: Is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. Repeat sequences in gp41, HR1, and HR2 then interact, causing
4851-470: Is designed to detect both the p24 antigen and HIV antibodies in a single test. Combination tests can detect HIV as early as 2–6 weeks after infection, and are recommended in laboratory testing. Nucleic-acid-based tests amplify and detect one or more of several target sequences located in specific HIV genes, such as HIV-I GAG, HIV-II GAG, HIV-env, or the HIV-pol. Since these tests are relatively expensive,
4998-411: Is determining the "cut-off" point between a positive and negative result. Researchers from Columbia University have produced an ELISA test dongle capable of testing for HIV and syphilis . It is compatible to any smartphone or computer without additional support or battery power, and takes some fifteen minutes to analyse a drop of blood. The units cost approximately $ 34 each to manufacture. Like
5145-489: Is diagnosed separately from HIV. The eclipse period is a variable period starting from HIV exposure in which no existing test can detect HIV. The median duration of the eclipse period in one study was 11.5 days. The window period is the time between HIV exposure and when an antibody or antigen test can detect HIV. The median window period for antibody/antigen testing is 18 days. Nucleic acid testing (NAT) further reduces this period to 11.5 days. Performance of medical tests
5292-410: Is estimated to be about 1 in 250,000 in a low risk population. Testing post-exposure is recommended immediately and then at six weeks, three months, and six months. HIV tests HIV tests are used to detect the presence of the human immunodeficiency virus (HIV), the virus that causes HIV/AIDS , in serum , saliva , or urine . Such tests may detect antibodies , antigens , or RNA . AIDS
5439-424: Is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities. Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV. HIV-1 testing
5586-416: Is fastened to the wall. Then new oligonucleotides that bind at several locations to this RNA are added, and other oligonucleotides that bind at several locations to those oligonucleotides. This is done to amplify the signal. Finally, oligonucleotides that bind to the last set of oligonucleotides and that are bound to an enzyme are added; the enzyme action causes a color reaction , which allows quantification of
5733-464: Is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on
5880-399: Is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive,
6027-447: Is largely confined to West Africa . HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120 nm , around 100,000 times smaller in volume than a red blood cell . It is composed of two copies of positive- sense single-stranded RNA that codes for the virus' nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24 . The single-stranded RNA
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6174-496: Is leveled by a surfactant called sodium lauryl sulfate . Some commercially prepared Western blot test kits contain the HIV proteins already on a cellulose acetate strip. Once the proteins are well-separated, they are transferred to a membrane and the procedure continues similar to an ELISA: the person's diluted serum is applied to the membrane and antibodies in the serum may attach to some of the HIV proteins. Antibodies that do not attach are washed away, and enzyme-linked antibodies with
6321-612: Is more likely, leading to immunodeficiency. Three groups of HIV-1 have been identified on the basis of differences in the envelope ( env ) region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes (or clades ), based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in
6468-485: Is often described in terms of: All diagnostic tests have limitations, and sometimes their use may produce erroneous or questionable results. Nonspecific reactions, hypergammaglobulinemia , or the presence of antibodies directed to other infectious agents that may be antigenically similar to HIV can produce false positive results. Autoimmune diseases, such as systemic lupus erythematosus , have also rarely caused false positive results. Most false negative results are due to
6615-425: Is positive. The three-gene-product approach to western blot interpretation has not been adopted for public health or clinical practice. Tests in which less than the required number of viral bands are detected are reported as indeterminate: a person who has an indeterminate result should be retested, as later tests may be more conclusive. Almost all HIV-infected persons with indeterminate western blot results will develop
6762-561: Is present as both free virus particles and virus within infected immune cells . Research has shown (for both same-sex and opposite-sex couples) that HIV is not contagious during sexual intercourse without a condom if the HIV-positive partner has a consistently undetectable viral load . HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4 T cells), macrophages , and dendritic cells . HIV infection leads to low levels of CD4 T cells through
6909-529: Is referred to as co-infection. HIV-2 seems to have lower mortality rates, less severe symptoms and slower progression to AIDS than HIV-1 alone or the co-infection. In co-infection, however, this is largely dependent on which virus was contracted first. HIV-1 tends to out compete HIV-2 for disease progression. Co-infection seems to be a growing problem globally as time progresses, with most cases being identified in West African countries, as well as some cases in
7056-428: Is then applied to the plate, followed by another wash. This secondary antibody is chemically linked in advance to an enzyme . Thus the plate will contain enzyme in proportion to the amount of secondary antibody bound to the plate. A substrate for the enzyme is applied, and catalysis by the enzyme leads to a change in color or fluorescence. ELISA results are reported as a number; the most controversial aspect of this test
7203-443: Is therefore not possible to conclude that blood rejected for transfusion because of a positive ELISA antibody test is in fact infected with HIV. Sometimes, retesting the donor in several months will produce a negative ELISA antibody test. This is why a confirmatory western blot is always used before reporting a "positive" HIV test result. Rare false positive results due to factors unrelated to HIV exposure are found more often with
7350-412: Is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase , proteases , ribonuclease and integrase . A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the viral envelope , that is composed of the lipid bilayer taken from the membrane of
7497-534: Is unknown how often such mixed packaging occurs under natural conditions. Bonhoeffer et al. suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of
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#17327653010067644-638: The African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus, which is present at high levels in the host's blood, but evokes only a mild immune response, does not cause the development of simian AIDS, and does not undergo the extensive mutation and recombination typical of HIV infection in humans. In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as rhesus or cynomologus macaques ),
7791-544: The CCR5-Δ32 mutation are resistant to infection by the R5 virus, as the mutation leaves HIV unable to bind to this co-receptor, reducing its ability to infect target cells. Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are present in the seminal fluid , which enables the virus to be transmitted from a male to his sexual partner . The virions can then infect numerous cellular targets and disseminate into
7938-445: The adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell. Entry to the cell begins through interaction of the trimeric envelope complex ( gp160 spike) on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4 , but others are known to interact) on
8085-421: The gag polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the protease inhibitor class. The various structural components then assemble to produce a mature HIV virion. Only mature virions are then able to infect another cell. The classical process of infection of
8232-514: The microtubule -based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome. HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used. DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when
8379-403: The phylogenetic tree representing the lineage of the M group of HIV-1. Co-infection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and
8526-623: The sooty mangabey , a vulnerable West African primate. HIV-1 viruses can be further stratified into groups M, N, O, and P. Among these, HIV-1 group M viruses are the most prevalent, infecting nearly 90% of people living with HIV and are responsible for the global AIDS pandemic . Group M can be further subdivided into subtypes based on genetic sequence data. Certain subtypes are known for their increased virulence or drug resistance to different medications used to treat HIV. HIV-2 viruses are generally considered to be less virulent and less transmissible than HIV-1 M group viruses, although HIV-2
8673-438: The α -chemokine receptor, CXCR4 , for entry. Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry. The α -chemokine SDF-1 , a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down-regulating the expression of CXCR4 on the surface of HIV target cells. M-tropic HIV-1 isolates that use only
8820-427: The β -chemokine receptor, CCR5 , for entry and are thus able to replicate in both macrophages and CD4 T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4 cells become depleted in
8967-587: The CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that use both, X4R5. However, the use of co-receptors alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection and HIV can also infect a subtype of myeloid dendritic cells , which probably constitute a reservoir that maintains infection when CD4 T cell numbers have declined to extremely low levels. Some people are resistant to certain strains of HIV. For example, people with
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#17327653010069114-405: The DIS (dimerization initiation signal) hairpin is exposed. The formation of the gRNA dimer is mediated by a 'kissing' interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly. The labile gRNA dimer has been also reported to achieve
9261-531: The ELISA procedure, the western blot is an antibody detection test. However, unlike the ELISA method, the viral proteins are separated first and immobilized. In subsequent steps, the binding of serum antibodies to specific HIV proteins is visualized. Specifically, cells that may be HIV-infected are opened and the proteins within are placed into a slab of gel, to which an electric current is applied. Different proteins will move with different speeds in this field, depending on their size, while their electrical charge
9408-416: The ELISA test than with the western blot. False positives may be associated with medical conditions such as recent acute illnesses and allergies. A rash of false positive tests in the fall of 1991 was initially blamed on the influenza vaccines used during that flu season, but further investigation traced the cross-reactivity to several relatively non-specific test kits. A false positive result does not indicate
9555-419: The HIV env gene, allows the virus to attach to target cells and fuse the viral envelope with the target cell's membrane releasing the viral contents into the cell and initiating the infectious cycle. As the sole viral protein on the surface of the virus, the envelope protein is a major target for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans . The density
9702-402: The HIV control program for public health at Seattle King county, reported OraQuick failed to spot at least 8 percent of 133 people found to be infected with a comparable diagnostic test. Strategies implemented to determine quality control and false positive rates were implemented. It is to be understood that any reactive OraQuick test result is a preliminary positive result and will always require
9849-551: The HIV prevalence rises. Thus a positive test in a high-risk population, such as people who frequently engage in unprotected anal intercourse with unknown partners, is more likely to correctly represent HIV infection than a positive test in a very low-risk population, such as unpaid blood donors. Many studies have confirmed the accuracy of current methods of HIV testing in the United States , reporting false-positive rates of 0.0004 to 0.0007 and false-negative rates of 0.003 in
9996-441: The HIV protein-coding sequences is translated. Mature HIV mRNAs are exported from the nucleus into the cytoplasm , where they are translated to produce HIV proteins, including Rev . As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus. Some of these full-length RNAs function as mRNAs that are translated to produce
10143-570: The HIV virological synapse in vivo . The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies. HIV differs from many viruses in that it has very high genetic variability . This diversity is a result of its fast replication cycle , with the generation of about 10 virions every day, coupled with a high mutation rate of approximately 3 x 10 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase. This complex scenario leads to
10290-596: The International AIDS Society publish lists of the most important of these; first year listing 80 common mutations, and the latest year 93 common mutations, and made available through the Stanford HIV RT and Protease Sequence Database . HIV The human immunodeficiency viruses ( HIV ) are two species of Lentivirus (a subgroup of retrovirus ) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS),
10437-512: The Ivory Coast. Each of these HIV-2 strains, for which humans are probably dead-end hosts , is most closely related to SIVsmm strains from sooty mangabeys living in the same country where the human infection was found. HIV-2 diagnosis can be made when a patient has no symptoms but positive blood work indicating the individual has HIV. The Multispot HIV-1/HIV-2 Rapid Test is currently the only FDA approved method for such differentiation between
10584-526: The LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into microRNAs that regulate the apoptosis genes ERCC1 and IER3 . The rev protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The vif protein (p23) prevents the action of APOBEC3G (a cellular protein that deaminates cytidine to uridine in
10731-578: The National Association of Community Health Centers implemented a model for offering free, rapid HIV testing to all patients between the ages of 13 and 64 during routine primary medical and dental care visits. The program increased testing rates, with 66% of the 17,237 patients involved in the study agreeing to testing (56% were tested for the first time). In September 2010, New York became the first state to require that hospitals and primary care providers offer an HIV test to all patients between
10878-491: The RT-PCR test, viral RNA is extracted from the patient's plasma and is treated with reverse transcriptase (RT) to convert the viral RNA into cDNA . The polymerase chain reaction (PCR) process is then applied, using two primers unique to the virus's genome. After PCR amplification is complete, the resulting DNA products are hybridized to specific oligonucleotides bound to the vessel wall, and are then made visible with
11025-433: The U.S.: Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition,
11172-545: The US, the Food and Drug Administration requires that all donated blood be screened for several infectious diseases, including HIV-1 and HIV-2, using a combination of antibody testing ( EIA ) and more expeditious nucleic acid testing (NAT). These diagnostic tests are combined with careful donor selection. As of 2001 , the risk of transfusion-acquired HIV in the US was approximately one in 2.5 million for each transfusion. Tests used for
11319-465: The USA. A study found that individuals who contract HIV-2 before HIV-1 tend to have a slower rate of disease progression, suggesting that the immune response to HIV-2 may limit the proliferation of HIV-1. If a pregnant mother is exposed, screening is performed as normal. If HIV-2 is present, a number of perinatal ART drugs may be given as a prophylactic to lower the risk of mother-to-child transmission. After
11466-414: The United States has been screened with nucleic-acid-based tests, shortening the window period between infection and detectability of disease to a median of 17 days (95% CI, 13–28 Days, assumes pooling of samples). A different version of this test is intended for use in conjunction with clinical presentation and other laboratory markers of disease progress for the management of HIV-1 -infected patients. In
11613-559: The United States was in 1987. The first confirmed case of HIV-2 was a Portuguese man who was treated at the London Hospital for Tropical Diseases and later died in 1987. He was believed to have been exposed to the disease in Guinea-Bissau where he lived between 1956 and 1966. His pathological diagnosis at the time was cryptosporidiosis and enterovirus infection , but an analysis of his stored serum in 1987 found that he
11760-638: The United States, one emerging standard of care is to screen all patients for HIV in all health care settings. In 2006, the Centers for Disease Control (CDC) announced an initiative for voluntary, routine testing of all Americans aged 13–64 during health care encounters. An estimated 25% of infected individuals were unaware of their status; if successful, this effort was expected to reduce new infections by 30% per year. The CDC recommends elimination of requirements for written consent or extensive pre-test counseling as barriers to widespread routine testing. In 2006,
11907-604: The YBF380 variant reacted with an viral envelope antigen from SIVcpz rather than with those of Group M or Group O, indicating it was indeed a novel strain of HIV-1. As of 2015, fewer than 20 Group N infections have been recorded. The O ("Outlier") group has infected about 100,000 individuals located in West-Central Africa and is not usually seen outside of that area. It is reportedly most common in Cameroon, where
12054-446: The above listed therapies are being looked into as well, also showing variable effect depending on the types of therapies combined. While the mechanisms are not clearly understood for HIV-1 and HIV-2, it is known that they use different pathways and patterns, making the algorithms used to evaluate HIV-1 resistance-associated mutations irrelevant to HIV-2. Each virus can be contracted individually, or they can be contracted together in what
12201-528: The actual numbers vary depending on the testing population. This is because interpreting of the results of any medical test (assuming no test is 100% accurate) depends upon the initial degree of belief, or the prior probability that an individual has, or does not have a disease. Generally the prior probability is estimated using the prevalence of a disease within a population or at a given testing location. The positive predictive value and negative predictive value of all tests, including HIV tests, take into account
12348-409: The adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process,
12495-409: The addition of CCR5 co-receptor antagonists and fusion inhibitors . Choice of initial and/or second-line therapy for HIV-2 has not yet been defined. HIV-2 appears to be resistant to NNRTIs intrinsically, but may be sensitive to NRTIs, though the mechanism is poorly understood. Protease inhibitors have shown variable effect, while integrase inhibitors are also being evaluated. Combination regimens of
12642-423: The advent of AIDS. HIV-positive patients acquire an enormously broad spectrum of opportunistic infections, which was particularly problematic prior to the onset of HAART therapies; however, the same infections are reported among HIV-infected patients examined post-mortem following the onset of antiretroviral therapies. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be
12789-467: The ages of 13 and 64 years. An evaluation of the law's impact found that it increased testing significantly throughout the state. HIV antibody tests are specifically designed for routine diagnostic testing of adults; these tests are inexpensive and extremely accurate. Antibody tests may give false negative (no antibodies were detected despite the presence of HIV) results during the window period , hence an interval of three weeks to six months between
12936-403: The animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection. Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host. SIVcpz appears to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to
13083-399: The antibodies. The combination of these two methods is highly accurate The UNAIDS/WHO policy statement on HIV Testing states that conditions under which people undergo HIV testing must be anchored in a human rights approach that pays due respect to ethical principles . According to these principles, the conduct of HIV testing of individuals must be Considerable controversy exists over
13230-504: The blood is screened by first pooling some 8–24 samples and testing these together; if the pool tests positive, each sample is retested individually. Although this results in a dramatic decrease in cost, the dilution of the virus in the pooled samples decreases the effective sensitivity of the test, lengthening the window period by four days (assuming a 20-fold dilution, ~20hr virus doubling time, detection limit 50 copies/ml, making limit of detection 1,000 copies/ml). Since 2001, donated blood in
13377-454: The capability to attach to the person's antibodies determine to which HIV proteins the person has antibodies. There are no universal criteria for interpreting the western blot test: The number of viral bands that must be present may vary. If no viral bands are detected, the result is negative. If at least one viral band for each of the GAG, POL , and ENV gene-product groups are present, the result
13524-592: The cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III). HIV-1 is more virulent and more infective than HIV-2, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2
13671-470: The cell types a virus infects. HIV can infect a variety of immune cells such as CD4 T cells , macrophages , and microglial cells . HIV-1 entry to macrophages and CD4 T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with chemokine co-receptors . Macrophage-tropic (M-tropic) strains of HIV-1, or non- syncytia -inducing strains (NSI; now called R5 viruses ) use
13818-414: The child is born, a standard six-week regimen of these prophylactics should be initiated. Breast milk may also contain viral particles of HIV-2; therefore, breastfeeding is strictly advised against. The rapid evolution of HIV can be attributed to its high mutation rate. During the early stages of mutation, evolution appears to be neutral due to the absence of an evolutionary response. However, when examining
13965-500: The client between 15 and 30 minutes. Furthermore, when an HIV-positive result is communicated, the HTC provider can offer appropriate linkages for prevention, care, and treatment. Testing that has only a number attached to the specimen that will be delivered for testing. Items that are confirmed positive will not have the HIV infected individual's name attached to the specimen. Sites that offer this service advertise this testing option. In
14112-459: The collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid. After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During
14259-411: The counts may fluctuate in healthy people, depending on recent infection status, nutrition, exercise, and other factors. Women tend to have somewhat lower counts than men. As a result of an increase in false positive rates with rapid oral HIV testing in 2005, New York City's Department of Health and Mental Hygiene added the option of testing finger-stick whole blood after any reactive result, before using
14406-447: The development of AIDS. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period . Lentiviruses are transmitted as single-stranded , positive- sense , enveloped RNA viruses . Upon entry into
14553-577: The development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation ( radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress
14700-459: The diagnosis of HIV infection in a particular person require a high degree of both sensitivity and specificity . In the United States, this is achieved using an algorithm combining two tests for HIV antibodies. If antibodies are detected by an initial test based on the ELISA method, then a second test using the western blot procedure determines the size of the antigens in the test kit binding to
14847-526: The early stages of infection. This preference of the virus to transmit its stored genome copies explains why HIV evolves more quickly within the host than between hosts. HIV is evolving toward a milder form, but it is still "an awfully long way" from no longer being deadly, with severe variants still appearing. Isolates of HIV-1 and HIV-2 with resistance to antiretroviral drugs arise through natural selection and genetic mutations, which have been tracked and analyzed. The Stanford HIV Drug Resistance Database and
14994-405: The ethical obligations of health care providers to inform the sexual partners of individuals infected with HIV that they are at risk of contracting the virus. Some legal jurisdictions permit such disclosure, while others do not. More state funded testing sites are now using confidential forms of testing. This allows for monitoring of infected individuals easily, compared to anonymous testing that has
15141-413: The facilities to securely store such information, and schools generally do not have the capacity to provide counseling for HIV-positive pupils. In South Africa, anyone over the age of 12 may request an HIV test without parental knowledge or consent. Some 80,000 pupils in three provinces were tested under this programme before it ended. The CD4 T-cell count is not an HIV test, but rather a procedure where
15288-415: The general population. The p24 antigen test detects the presence of the p24 protein of HIV (also known as CA), the capsid protein of the virus. Monoclonal antibodies specific to the p24 protein are mixed with the person's blood. Any p24 protein in the person's blood will stick to the monoclonal antibody and an enzyme-linked antibody to the monoclonal antibodies to p24 causes a color change if p24
15435-431: The generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens,
15582-576: The generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching. HIV-1 infection causes chronic inflammation and production of reactive oxygen species . Thus, the HIV genome may be vulnerable to oxidative damage , including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses
15729-552: The genetic information that is transmitted from parental to progeny genomes. Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy . Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It
15876-415: The immune response to target epitopes. The RNA genome consists of at least seven structural landmarks ( LTR , TAR , RRE , PE, SLIP, CRS, and INS), and nine genes ( gag , pol , and env , tat , rev , nef , vif , vpr , vpu , and sometimes a tenth tev , which is a fusion of tat , env and rev ), encoding 19 proteins. Three of these genes, gag , pol , and env , contain information needed to make
16023-472: The inexpensive enzyme immunoassay screening tests indicates that, in 1,000 HIV test results of healthy individuals, about 15 of these results will be a false positive . Confirming the test result (i.e., by repeating the test, if this option is available) could reduce the ultimate likelihood of a false positive to about 1 result in 250,000 tests given. The sensitivity rating, likewise, indicates that, in 1,000 test results of HIV infected people, 3 will actually be
16170-521: The integrated DNA provirus is transcribed into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a pseudodiploid form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized by a tandem three-way junction within the gRNA monomer, in which the SD and AUG hairpins , responsible for splicing and translation respectively, are sequestered and
16317-491: The number of CD4 T-cells in the blood is determined. A CD4 count does not check for the presence of HIV. It is used to monitor immune system function in HIV-positive people. Declining CD4 T-cell counts are considered to be a marker of progression of HIV infection. A normal CD4 count can range from 500 cells/mm3 to 1000 cells/mm3. In HIV-positive people, AIDS is officially diagnosed when the count drops below 200 cells/μL or when certain opportunistic infections occur. This use of
16464-410: The patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system . In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus. T-tropic strains of HIV-1, or syncytia -inducing strains (SI; now called X4 viruses ) replicate in primary CD4 T cells as well as in macrophages and use
16611-448: The person has not been infected with HIV. It may take several months after HIV infection for the antibody response to reach detectable levels, during which time rapid testing for antibodies to HIV will not be indicative of true infection status. For most people, HIV antibodies reach a detectable level after two to six weeks. Although these tests have high specificity, false positives do occur. Any positive test result should be confirmed by
16758-429: The prior probability of having a disease along with the accuracy of the testing method to determine a new degree of belief that an individual has or does not have a disease (also known as the posterior probability ). The chance that a positive test accurately indicates an HIV infection increases as the prevalence or rate of HIV infection increases in the population. Conversely, the negative predictive value will decrease as
16905-406: The remaining 5.3% were composed of other subtypes and CRFs. Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes. The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009. The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006. HIV-2's closest relative is SIVsm,
17052-425: The reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes. The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of
17199-519: The single-stranded viral DNA and/or interferes with reverse transcription ). The vpr protein (p14) arrests cell division at G2/M . The nef protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules. Nef also interacts with SH3 domains . The vpu protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called
17346-412: The site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase diffusion of virions, and clustering of HIV entry receptors on the target cell towards the contact zone. Cell-to-cell spread is thought to be particularly important in lymphoid tissues , where CD4 T cells are densely packed and likely to interact frequently. Intravital imaging studies have supported the concept of
17493-673: The specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person. HIV deaths in 2014 excluding
17640-483: The standard method for diagnosing HIV-1 infection. A large study of HIV testing in 752 U.S. laboratories reported a sensitivity of 99.7% and specificity of 98.5% for enzyme immunoassay, and studies in U.S. blood donors reported specificities of 99.8% and greater than 99.99%. With confirmatory Western blot, the chance of a false-positive identification in a low-prevalence setting is about 1 in 250 000 (95% CI, 1 in 173 000 to 1 in 379 000). The specificity rate given here for
17787-556: The structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles. HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 will bind to any appropriate RNA. HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself. Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV ). Upon infection and replication catalyzed by reverse transcriptase, recombination between
17934-496: The structural proteins for new virus particles. For example, env codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, tat , rev , nef , vif , vpr , and vpu (or vpx in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The two tat proteins (p16 and p14) are transcriptional transactivators for
18081-427: The target cell surface. Gp120 binds to integrin α 4 β 7 activating LFA-1 , the central integrin involved in the establishment of virological synapses , which facilitate efficient cell-to-cell spreading of HIV-1. The gp160 spike contains binding domains for both CD4 and chemokine receptors. The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120
18228-413: The target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded enzyme, reverse transcriptase , that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded enzyme, integrase , and host co-factors . Once integrated,
18375-437: The test is often used in combination with an antibody test to effectively cover a longer portion of the window period. It is less useful as a standalone test, as it has low sensitivity and only works during the early time period after infection. The presence of p24 antigen diminishes as the body increases production of antibodies to the p24 protein, making p24 more difficult to detect later. A combination, or 4th generation assay,
18522-506: The time of HIV exposure and the production of measurable antibodies to HIV seroconversion is implemented. Most people develop detectable antibodies approximately 18 to 30 days after exposure, although some do seroconvert later. The vast majority of people (99%) have detectable antibodies by two months after HIV exposure. During the window period, an infected person can transmit HIV to others although their HIV infection may not be detectable with an antibody test. Antiretroviral therapy during
18669-414: The two HIV envelope glycoproteins, gp41 and gp120 . These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as
18816-484: The two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle
18963-506: The two viruses. Recommendations for the screening and diagnosis of HIV has always been to use enzyme immunoassays that detect HIV-1, HIV-1 group O, and HIV-2. When screening the combination, if the test is positive followed by an indeterminate HIV-1 western blot , a follow-up test, such as amino acid testing, must be performed to distinguish which infection is present. According to the NIH, a differential diagnosis of HIV-2 should be considered when
19110-570: The viral DNA into the host cell's genome is carried out by another viral enzyme called integrase . The integrated viral DNA may then lie dormant, in the latent stage of HIV infection. To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF- κ B (nuclear factor kappa B), which is upregulated when T cells become activated. This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection. During viral replication,
19257-451: The viral RNA in the original sample. Monitoring the effects of antiretroviral therapy by serial measurements of plasma HIV-1 RNA with this test has been validated for patients with viral loads greater than 25,000 copies per milliliter. The South African government announced a plan to start screening for HIV in secondary schools by March 2011. This plan was cancelled due to concerns it would invade pupils' privacy, schools typically don't have
19404-536: The virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host, but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected. The HIV virion enters macrophages and CD4 T cells by
19551-405: The virus in several different individuals, convergent mutations can be found appearing in these viral populations independently. HIV evolution within a host influences factors including the virus' set-point viral load . If the virus has a low set-point viral load, the host will live longer, and there is a greater probability that the virus will be transmitted to another individual. If the virus has
19698-425: The virus is captured in the mucosa by DCs. The presence of FEZ-1 , which occurs naturally in neurons , is believed to prevent the infection of cells by HIV. HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by pH -independent, clathrin-mediated endocytosis of HIV-1 has also been reported and
19845-463: The virus may become latent , allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed , producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from
19992-403: The virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the antisense cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus . The integration of
20139-540: The virus. This virus has also lost a function of the nef gene that is present in most SIVs. For non-pathogenic SIV variants, nef suppresses T cell activation through the CD3 marker. Nef 's function in non-pathogenic forms of SIV is to downregulate expression of inflammatory cytokines , MHC-1 , and signals that affect T cell trafficking. In HIV-1 and SIVcpz, nef does not inhibit T-cell activation and it has lost this function. Without this function, T cell depletion
20286-475: The whole organism. However, a selection process leads to a predominant transmission of the R5 virus through this pathway. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants that can infect a variety of T cells through CXCR4. These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark
20433-463: The window period can delay the formation of antibodies and extend the window period beyond 12 months. This was not the case with patients that underwent treatment with post-exposure prophylaxis (PEP). Those patients must take ELISA tests at various intervals after the usual 28-day course of treatment, sometimes extending outside of the conservative window period of 6 months. The enzyme-linked immunosorbent assay (ELISA), or enzyme immunoassay (EIA),
20580-509: The window period. Tests selected to screen donor blood and tissue must provide a high degree of confidence that HIV will be detected if present (that is, a high sensitivity is required). A combination of antibody , antigen and nucleic acid tests are used by blood banks in Western countries. The World Health Organization estimated that, as of 2000 , inadequate blood screening had resulted in 1 million new HIV infections worldwide. In
20727-454: Was found to be strongly associated with rapid progression to AIDS in Cuba . This is not thought to be a complete or final list, and further types are likely to be found. The 'N' stands for "non-M, non-O". This group was discovered by a Franco-Cameroonian team in 1998, when they identified and isolated the HIV-1 variant strain, YBF380, from a Cameroonian woman who died of AIDS in 1995. When tested,
20874-537: Was infected with HIV-2. Many test kits for HIV-1 will also detect HIV-2. There are eight known HIV-2 groups, designated A to H. Of these, only groups A and B are pandemic . Group A is found mainly in West Africa, but has also spread to Angola, Mozambique, Brazil, India, Europe, and the US. Despite the presence of HIV-2 globally, Group B is mainly confined to West Africa. HIV-2 is closely related to SIV endemic in sooty mangabeys ( Cercocebus atys atys ) (SIVsmm),
21021-540: Was present in the sample. In blood donation screening, this test is no longer used routinely in the US or the EU since the objective was to reduce the risk of false negatives in the window period. Nucleic acid testing (NAT) is more effective for this purpose, and p24 antigen testing is no longer indicated if a NAT test is performed. In general diagnostics, p24 antigen tests are used for early detection of HIV, as p24 antigen rises soon after infection relative to antibodies, and
21168-448: Was recently suggested to constitute the only route of productive entry. Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow
21315-647: Was reported to have greater similarity to SIVgor, than SIVcpz. The virus had been isolated from a Cameroonian woman residing in France who was diagnosed with HIV-1 infection in 2004. The scientists reporting this sequence placed it in a proposed Group P "pending the identification of further human cases". HIV-2 is mostly found in Africa, and therefore less recognized elsewhere in the world. The first identification of HIV-2 occurred in 1985 in Senegal by microbiologist Souleymane Mboup and his collaborators. The first case in
21462-451: Was the first screening test commonly employed for HIV. It has a high sensitivity. In an ELISA test, a person's serum is diluted 400-fold and applied to a plate to which HIV antigens have been attached. If antibodies to HIV are present in the serum, they may bind to these HIV antigens. The plate is then washed to remove all other components of the serum. A specially prepared " secondary antibody " – an antibody that binds to human antibodies –
21609-779: Was the source of pre-1960 pandemic viruses, originated in the 1920s in Léopoldville , the Belgian Congo , today known as Kinshasa, which is now the capital of the Democratic Republic of Congo (DRC). Its zoonotic origin is the SIVcpz strain, which infects chimpanzees. The M group is subdivided further into clades , called subtypes, that are also given a letter. There are also "circulating recombinant forms" or CRFs derived from genetic recombination between viruses of different subtypes which are in addition each given
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