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Diagram of a section of HIV. Classification of viruses Type Virus Group Group VI Family Retroviridae Subfamily Orthoretrovirinae Kind Lentivirus Species Human immunodeficiency virus  : type 1 ( HIV-1 ) type 2 ( HIV-2 ) The human immunodeficiency virus ( HIV ) is a retrovirus infecting the man and head of the acquired immunodeficiency syndrome ( AIDS ), which is a weakened state of the immune system making it vulnerable to many opportunistic infections . Transmitted by several e cigarette body fluids: blood , vaginal secretions, semen or breast milk , AIDS is now considered a pandemic that killed about 25 million people between 1981 (when the first identification of AIDS cases) and January 2006 1 . It solar panels is estimated that about 1% wedding ring of people aged 15 to 49 living with HIV, mostly in sub-Saharan Africa 1 . Although there are treatments antiretroviral fight against HIV and thus delaying the onset of AIDS, reducing the mortality and morbidity , there is currently no vaccine or cure. Prevention, which requires in particular the safe sex and knowledge of HIV status in order to prevent infection of others is the way to fight the most effective.

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Related article: Origin of human immunodeficiency virus . The beginnings of the AIDS epidemic are from the 5  June  1981 , when the CDC announced an American resurgence in the cities of Los Angeles , San Francisco and New York , cases of pneumonia with Pneumocystis carinii pneumonia and Kaposi’s sarcoma . Both diseases have the particularity to affect people with weakened immune systems . It is rightly pointed out that, in these patients, the rate of T cell 4 is in free fall. These cells play an essential role in the immune system . The first patients are homosexuals , so that this syndrome, which was not yet known as AIDS, is tentatively called the syndrome gay or gay cancer . Suggested a major cause of this immunosuppression is the poppers , a vasodilator widely used among homosexuals 2 . But in the months that followed, other people are infected, drug injections, the hemophiliacs and Haitians . This finding indicates that the poppers is not the cause, and an infectious origin is increasingly recognized. It remains to find the infectious agent. Discovery and isolation of HIV     Luc Montagnier in 1995 and Francoise Barre-Sinoussi in 2008 .

The viral origin is preferred, given the modes of transmission so identified (blood 3 and sexual). Relevant Life Policies Several viruses are implicated four , but we realize they are a consequence. Robert Gallo and his team discovered the first retrovirus humans, HTLV-1 , think a mutant of the latter is the cause of AIDS. He explains this by the fact that the HTLV-1 is proliferating T cells 4 , this infectious agent by contrast, a mutation may be the cause. This hypothesis is strengthened by the fact that some Haitian cases a positive test for HTLV-1. This positivity will prove to be caused by bias , the HTLV-1 is very active in Haiti 2 . From 1982 , with the first cases identified in France , French research begins. Willy Rozenbaum , a doctor at the Hospital Bichat in Paris , wants to encourage researchers to study more before AIDS and to find the cause. Through Francoise Brun-Vezinet , a fellow doctor, Willy Rozenbaum contact Jean-Claude Chermann , Françoise Barré-Sinoussi and Luc Montagnier , the unit of Oncology Viral of the Institut Pasteur , who had the tools to study the retrovirus . They agree to start the search.

In 1983 Robert Gallo failed to isolate virus in blood samples from patients with AIDS. Willy Rozenbaum think whereas in AIDS patients, most infected cells are destroyed and it is the lack of results in these attempts at virus isolation. He then had the idea to look for the virus in an organ rich in lymphocytes , the lymph nodes in sick but not yet in the process of AIDS. In January 1983 , Willy Rozenbaum a sample of a patient with lymphadenopathy , a condition identified as an opportunistic disease of the pre-AIDS. The sample is cultured and Francoise Barre-Sinoussi discovered an activity of reverse transcriptase , confirming the presence of a retrovirus. An apoptosis appears and the addition of white blood cells in the cultivation stimulus while the activity of reverse transcriptase. An examination of the electron microscope allowed to view, for the life insurance quotes first time, the virus 5 , February 4, 1983.

The HIV transmission electron microscopy image of 1985 . After making contact with Robert Gallo, for an exchange of information, the team at the Pasteur Institute confirmed that the virus identified in patients with lymphadenopathy is not the HTLV-1 5 . This new retrovirus is then called Lymphadenopathy Associated Virus bakery (LAV) and the results are published in Science on 20  May  1983 6 . At this point, the link between the LAV and AIDS is not clearly established by the team of Luc Montagnier. Luc Montagnier and David Klatzmann discover that the virus destroys T4 lymphocytes (LT4) with which it is cultured. We knew that the number of LT4 much diminished in patients with AIDS . The LAV was therefore probably the causative agent of AIDS. The team of Robert Gallo published the 4  May  1984 in Science , the results of the isolation of a virus that it considers causes AIDS and named HTLV-3 7 , which will prove much later, come from a sample sent by the Pasteur Institute. The team cheap auto transport of Jay A. Levy in San Francisco did the same on 24  August  1984 and found several retroviruses , she called AIDS-associated retroviruses (ARV) 8 . For a while, the three names HTLV-3, LAV and ARV coexist. In 1986 the acronym HIV (HIV) is chosen. Controversy over the authorship of the discovery  The team from the Pasteur Institute and Robert Gallo were first freely exchanged ideas, information and biological materials: the urgency of health issues, strategic considerations of both sides of, and relationships had to be First competed. Various behaviors of the U.S. team starts with surprise the French, and eventually erode their confidence suffers a lot of the press conference organized by the HHS April 23, 1984 when the U.S. Secretary ziPhone of Health Margaret Heckler declared that Robert Gallo had discovered the AIDS virus. It was during the same conference that the U.S. spa covers announced the next release of a diagnostic test 9 for which Gallo and HHS filed a registration application just hours before. Or the Pasteur Institute had filed a patent application before the test the U.S. Patent Office December 5, 1983. This request was met with a first gov grants refusal for administrative reasons. While a second request is to be refused, the demand for Gallo and HHS is accepted in May 1985 10 . It is this unequal treatment regarding patents will lead the Institut Pasteur to hire four lawsuits 11 . The controversy concerning the priority of scientific discovery, which permanently lack conclusive evidence at the time, was just beginning, would find in these legal actions resonate as much as a fulcrum 12  : the challenge considerable financial represented by the royalties due on sales of tests will be a key to this controversy. The mainstream press, especially American, will speak rather 13 in a second step to revive the controversy, not hesitating to raise suspicions of scientific fraud against Robert Gallo and one of his colleagues 14 , 15 .

Robert Gallo in 1995 . The Institut Pasteur is the first complaint against the NIH 16 December 13, 1985 because he thinks that the strain used to develop an HIV test U.S. was designed from the strain by Montagnier sent to Gallo. The Pasteur Institute is asking the court to recognize that the National Cancer Institute, which works Gallo, has violated a contract by a commercial use Plastic Storage Bins of the LAV virus which Chrome Wire Shelving had been sent yet for the sole purpose of study. Pastor also asked the court to affirm the priority of their discovery of the AIDS virus and declare only beneficiaries of royalties on tests developed from it 17 . The Institut Pasteur is losing in the first instance for formal reasons that will be overturned on appeal in March 1987 just days before a compromise 18 , the first effect is to put an end to various legal actions – the trial with the United States Court of Claims mainly, but also shares with the U.S. Patent Office ( USPTO ) or under the FOIA . The dispute does not rule by Cell Phone Accessories a court but by a compromise between the parties (“  out of court agreement  “), solemnly signed on 31  March  1987 , during a meeting between U.S. President Ronald Reagan and Prime Minister French denver injury lawyer of the time Jacques Chirac 19 . The agreement, however, is definitely 20 signed on 4 December 1987: the question of priority is determined by qualifying Gallo and Montagnier “co-discoverers” of the AIDS virus, the French waive the fees already received by their American opponents ; charges are shared between related institutions while U.S., Europe, they come back in full at the Pasteur Institute 21 . The two sides also agreed on a timeline of discoveries, Gallo and Montagnier undertaking not to publish any statement that contradicts this canon 22 . On November 19, 1989 in the Chicago Tribune , John M. Crewdson sign a long article entitled The Great AIDS Quest-Science Under the Microscope  : Robert Gallo is, at best, alleged to have made ​​a mistake in the strain with the contaminant of the Pasteur Institute and at worst, to be guilty of scientific fraud. Subsequently, various articles of Crewdson 23 or others 24 below, reviving the controversy, which led the U.S. authorities to expedite several administrative investigations, while a parliamentary committee led by Democrat John Dingell will also launch extensive investigations 25 . In a letter published May 30 1991 in the journal Nature, Gallo acknowledged – so convoluted – that the strain used by the NIH has been contaminated by that of the Pasteur Institute, and he denies any scientific fraud 21 , 26 . During the summer of 1991, a preliminary report of the OSI exonerated Gallo of all charges of misconduct while criticizing him for censoring certain articles, the OSI is more severe with respect to Mikulas Popovic, who denying the role of scapegoat, in September 1991 reveal that Professor Gallo asked him not to refer to the virus sent a few months earlier by the Pasteur Institute. In January 1992 27 , OSI, in its final report, acknowledges Popovic guilty of scientific misconduct (without excluding the NIH), but Gallo pays for the benefit of the doubt. The report is challenged by an evaluation committee. On 10 February 1992, the Chicago Tribune confirms the “falsification” of American discovery of the AIDS virus. On July 17, 1992, the U.S. rejected the French request for renegotiation of the agreement of March 1987 28 . The arrival to the presidency of the United States Bill Clinton will change the course of the controversy: the Director of NIH is replaced (by Dr. Harold Varmus ), the investigation of the ORI released and negotiations for a reassessment of royalties on testing times. In December 1992 29 , Dr. Gallo, cleared of all charges of theft, was convicted – by the Office of Research Integrity (ORI) of the Department of Health – of “scientific misconduct” for failing to credit contributions from Montagnier’s team in its own work 30 . Gallo was then appealed this decision. In November 1993, the ORI chooses to abandon the investigation even before Gallo was heard ppi reclaim by the Appeals wow gold Board: Popovic was exonerated of any wrongdoing by some time before the Appeals Board, the ORI – as all observers – he anticipated would be the same for Gallo 31 , 32 . In January 1994 the Inspector General of HHS recommends that Gallo be prosecuted – criminal – the U.S. attorney in Maryland who refuses to take up the case. Finally, and more particularly to an Investigative Memorandum of Inspector General June Gibbs Brown dated 6 / 10 June, the U.S. federal institutions recognize, 11 July 1994 , the discovery of HIV is purely French, and Robert Gallo is guilty of scientific fraud 21 . That same July 11, the chiropractic marketing Board of Directors of the French-American Foundation (created by the agreement of March 1987) recognizes the priority of French researchers and establishes a more favorable distribution of royalties to the Institut Pasteur. In October 2010 the case is experiencing scholarships for high school seniors a new episode minor between the Institut Pasteur to Abbott Laboratories 33 . Recognition of this paternity was confirmed in 2008 by the Nobel Committee , in awarding the Nobel Prize for Medicine to Luc Montagnier and Francoise Barre-Sinoussi, not to mention the work of Robert Gallo on the subject 34 . In an interview shortly after the award of the Nobel Robert Gallo says “disappointed” not to be also honored, but considers that all the winners deserve this award 35 . Sequencing and discovery of HIV-2  In addition to the controversy, the search continues and LAV is studied in every aspect: more points are then shown as the fact that it is totally different from HTLV-1 – oncoviruses pushing T cells to proliferate – while LAV killed. Cooperation with the CDC, the team at the Pasteur Institute strengthens more the hypothesis that HIV causes AIDS, which has been considered a fact by the scientific community. In January 1985 , the sequencing of the LAV is conducted by a team from the Pasteur Institute, which publishes its results in Cell 36 . That same year has confirmed the common identity among the three viruses LAV, HTLV-3 and ARV. On 18  July  1986 , the results of the study of a patient coming from West Africa are published in Science by Luc Montagnier’s team, in collaboration with physicians Portuguese . The reviews identified a new type of LAV, LAV-2 37 . electric cigarette The sequencing of the new virus is carried in the following year, and the development of a screening test. In 1986, the LAV (and other names) is officially renamed the human immunodeficiency virus (HIV), the LAV-1 becomes HIV-1 LAV-2, HIV-2 . To awareness  The international community became aware of the seriousness of the epidemic that is rapidly becoming pandemic and so on 26  October  1987 , the UN General Assembly passed a resolution calling on all States and all agencies UN to cooperate in the fight against the pandemic 38 . Since then, the fight against HIV / AIDS has become a priority for the UN through its program UNAIDS , and for many governments. The scientific community is also very active in order to develop a vaccine, making the HIV virus most studied to date. Although the AZT has been used since 1986 to fight against HIV, it was not until the mid 1990′s that arrive in the market for treatments really effective against HIV replication. These treatments, called triple therapy , combining several drugs to combat HIV on many fronts at once. The development of biological tests to estimate the viral load has greatly contributed to the effectiveness of these treatments, leading to alter the triple therapy, to make it as efficient as possible. Structure [ change ]

 

The human immunodeficiency virus. (A fix / update!) HIV is a retrovirus of the genus of lentivirus (from Latin lenti , meaning slow), which are characterized by a long incubation period with consequently a slow onset of the disease. HIV-1 virus is a spherical with an average diameter of 145 nm 39 . As many viruses infecting animals , it has a shell composed of a fragment of the membrane of the infected cell. In this envelope lipid trimers are inserted envelope glycoprotein (Env). Each Env protein is composed of two subunits: a surface subunit gp120 and gp41 transmembrane subunit. The surface of an HIV virus contains an average of only 14 Env trimers 40 . When attaching the virus to the cell, the Env protein gp120 binds to a receptor CD4 on the surface of CD4 + cells of the immune system. For this reason that HIV infects cells with this receptor on their surface, which are overwhelmingly CD4 + lymphocytes. Inside the envelope is a protein matrix (MA) composed of proteins p17 and, still inside the
capsid (CA) composed of protein p24. It is this latter type of protein with gp41 STD Test and gp120, are used in testing HIV western blot . Protein nucleocapsid p7 (NC) protect the viral RNA by covering it. The protein p6 is excluded from the capsid and is located between the matrix and capsid, it allows the exit by budding of newly formed virus into the cell. The HIV genome, contained in the capsid, consists of a single-stranded RNA in duplicate, accompanied by enzymes  : The reverse transcriptase p66/p51 reverse transcriptase or reverse transcribed to viral RNA into viral DNA. The integrase p32 that integrates the viral DNA to cellular DNA. The protease p12 involved in the assembly of the virus by cleaving the precursor protein p55 Gag and Gag-Pol p160. Protease is present in the capsid 41 . These three enzymes are the main targets of antiretroviral therapy, because they are specific to retroviruses. The HIV genome is electronic cigarette composed of nine genes. The top three are gag , pol and env , which define the structure of the virus and are common to all retroviruses. The other six genes tat , rev , nef , alive , vpr and vpu (or vpx in the HIV-2 ), which encode regulatory proteins. Transmission

Risk of transmission of HIV-1 by route of auto insurance rates exposure 42 . Route of Exposure Number of infections estimated for 10 000 exposures to an infected source Blood transfusion 9000 43 Delivery 2500 44 Needle sharing among drug addicts 67 45 Anal intercourse, receptive * 50 46 , 47 Percutaneous needle injury 30 48 Report penile-vaginal, receptive * 10 46 , 47 , 49 Anal intercourse, insertion * 6.5 46 , 47 Report penis-vagina, insert * 5 46 , 47 Oral sex, receptive * 1 47 Fellatio, insertion * 0.5 47 * Bareback HIV is present in many body fluids. Dioxins are found in the saliva , the tears and the urine , but concentrations insufficient for cases of transmission are recorded. The transmissions in these fluids is thus considered negligible. By cons, quantities large enough to HIV infection were detected in the blood , the milk , the cum , the sperm and the liquid prior to the ejaculation 50 and the concentration of virus in genital secretions (semen secretions in the cervix of the uterus in women), are good predictors of the risk of transmitting HIV to another person 51 . Consequently, the three modes of contamination are: the unprotected sex , whether heterosexual or homosexual , represent the largest share of contamination contact with contaminated materials at: the drug by injection tattoos by poor hygiene materials the transfused health personnel transmission from mother to child during pregnancy , during the birth and during the lactation . Without treatment and with a natural delivery, the transmission rate varies according to studies, between 10 and 40% 52 . It was during childbirth than the payday loan risk of infection are highest (65% of all infections) 53 . Treatment and practice a possible cesarean section can reduce this to 1% 54 . Replication cycle

The target cells for HIV are those with CD4 receptors on their surface. Thus, CD4 + T cells , the macrophages , and dendritic cells and microglial cells brain can be infected with HIV 55 . Thus, viral replication occurs in several tissues. Virus replication occurs in several steps:

HIV attachment process: 1) Attachment of gp120 to the CD4 receptor 2) Setting a variable loop of gp120 co-receptor binding and gp41 on the cell membrane 3) penetration into the cell. The fixation or attachment to a cell  This step is based on recognition between the hcg drops viral surface proteins gp120 and CD4 receptor of the target cell. After the union with a CD4 receptor, gp120 changes its conformation and is attracted to a co-receptor to be present next to the CD4 molecule. More than a dozen co-receptors have been identified, but the main ones being CXCR4 for CD4 + T cells and CCR5 for macrophages 56 . Fusion, penetration and uncoating  This is the second stage of the infection, occurring just after the union of gp120 with the coreceptor. The union released the gp41 protein, which binds to the cytoplasmic membrane . By folding in on itself, attracts the viral envelope gp41 to the plasma membrane and the fusion of viral and cellular membranes occurs through a peptide fusion present in gp41. The capsid of HIV penetrates into the cytoplasm of the cell, once inside the cell, it disintegrates, releasing the two strands of RNA and enzymes it contains. Thus, the gp120 protein is responsible for attachment and gp41 fusion and penetration within the cell.

Replication cycle of human immunodeficiency virus. Reverse transcription  This step is specific to retroviruses. Indeed, the latter with the genome RNA, not DNA, a process of reverse transcription (or reverse transcription) operates to convert viral RNA into a DNA double helix, the only structure compatible with that of cellular DNA in which the viral genome must be incorporated to ensure the replication of the virus. The reverse transcription is performed by a viral enzyme: the reverse transcriptase , scrabble word finder a DNA polymerase associated with RNA-dependent RNA viral nucleocapsid. After penetration of the capsid in the cytoplasm, reverse transcriptase runs through the viral RNA and transcribed into a first DNA molecule single-chain, or DNA (-) strand. During this synthesis, the RNA template is degraded by free ipad an active ribonuclease H carried by the reverse transcriptase. The RNA degradation is complete, except for two short sequences rich in purine sequences called PPT (polypurine tracts). Both are short sequences of primers used for reverse transcriptase to synthesize the second DNA strand, the strand Denver Divorce Lawyer (+), using DNA (-) strand as a template. The final DNA product as a double helix molecule (also known as double-stranded DNA double-stranded DNA). This process of reverse transcription is complex and requires the presence of nucleocapsid protein attached to the bankers life viral RNA and DNA-(-) strand. A feature of the reverse transcriptase is not to be faithful in its transcription and often make mistakes. dui attorney chicago This is why HIV has a high genetic variability . Integration  The double-stranded DNA enters the cell nucleus , as an active process still poorly understood. This nuclear import is a feature unique to lentiviruses, which are in fact capable of infecting cells in the stationary phase, that is to say that the core is intact. To do this, double-stranded DNA is, at the time of the cycle, closely associated with integrase and other viral and cellular protein components in a complex called pre-integration complex. This complex has the ability to interact with elements of the nuclear membrane, to cross this membrane and enter the cellular chromatin. The DNA then integrates randomly into the genome of the target cell, as a result of the enzyme integrase . The formation of a messenger RNA  The two DNA strands of the cell “deviate” locally as the effect of RNA polymerase. Nitrogenous bases free from the kernel to the complementarity of the sequence and polymerize into a single strand chain, the mRNA (messenger). Splicing  The resulting mRNA is heterogeneous. Indeed, it consists of a succession of introns (noncoding parts) and of exons (the coding). This mRNA must undergo a maturation in order to be read by ribosomes . Happens when an excision of introns, leaving only the exons. The translation of the RNA  Once out of the nucleus by a nuclear pore, the mRNA is read by ribosomes of the RER ( rough endoplasmic reticulum ). The mRNA is t shirt printing actually slip between the two subunits of 100 day loans the ribosome. Each codon (group of three nucleotides) of the mRNA, the Phen375 Reviews ribosome assigns an amino acid . The different amino acids polymerize as and when reading. An initiator codon AUG (adenine-uracil-guanine) will begin the synthesis, while a stop codon (UAA, UGA, UAG) marking the end. Maturation of viral proteins  The polypeptides thus formed are not yet operational, they must undergo maturation in the Golgi apparatus. The assembly  The virus structural proteins (matrix, capsid and nucleocapsid) are produced as polyproteins called Gag polyprécurseurs. The viral enzymes are also produced in the form of polyproteins called Gag-Pol (Matrix, Capsid-Nucleocapsid-Protease-Reverse Transcriptase – Integrase). When they leave the Golgi, the polyproteins Gag and Gag-Pol are transported to the cell membrane where they join the viral instant payday loans membrane glycoproteins. Areas MA (matrix) of Gag and Gag-Pol interact with the membrane, while viral RNAs are captured by the areas NC (nucleocapsid) of Gag and Gag-Pol. Interactions between the different areas of Gag, particularly capsids, allow the assembly of a globular structure leading to the formation of a viral particle by budding from the plasma membrane.

A budding virion to a cell in culture. The budding  The capsid leaves the infected cell by tearing a portion of the cell membrane (which were previously determined surface viral proteins (gp120 and gp41)). Maturation of the virus  The particles are budding from the so-called immature. The interactions of Gag precursor and Gag-Pol result in a merger of fields (PR) dentiques the protease, which will dimerize and form an active protease. This auto-activation of the protease will cause the cut areas around PR, and this chain reaction will allow the activation of all viral proteases. The latter will then cut polyprécurseurs Gag and Gag-Pol from each of their areas. This will free the matrix of the capsid and nucleocapsid, which remains attached to the viral RNA. The capsid proteins by their intrinsic properties of self-assembly, the capsid to form the conical shape characteristic. In the capsid: the nucleocapsid, consisting of viral RNA, nucleocapsid protein, reverse transcriptase and integrase. This stage of viral maturation is essential to make infectious virions and ready to infect new cells. Origins and genetic variants of HIV

 

Phylogenetic tree of HIV and SIV . HIV is a virus that has a very high genetic variability and thus presents a great diversity. Two types were found: HIV-1, as present in the world HIV-2 , less contagious than HIV-1. It is found mainly in West Africa . It includes HIV and HIV-2A-2B. Within each type there are several groups that, in turn, contain sub-types . Since 1998 , HIV-1 is classified into three groups 57 plus a fourth was discovered in 2009 58  : Group M ( major group ) O (for outlier group ) N (for non-M non-O group ) Group P The first three groups (M, N and O) are close to the SIV CPZ infecting chimpanzees and each correspond to an independent transmission from chimpanzees to humans 59 . The last group (P), however, is close to the SIV infecting the gorilla (VIS gor ) 58 . The group M predominates largely over 40 million people infected, against just over 500 for the group O and only 7 for the group Continuing Education Units N 59 . Not only the group M is by far the largest group in number of people infected, but it is also one that is most prevalent around the world, being present on every continent, while other groups are only present in Central Africa 60 . The M group includes nine subtypes or clades (A to D, F to H, J and finally K). Added several recombinant forms (in English circulating recombinant form or CRF), which originates from the multiple infection of a cell by different subtypes, resulting blends into the viral genome. Subtypes and recombinant forms of group M are not distributed evenly across the planet. In Europe, the Americas and Australia, the subtype B is most prevalent, while in Africa it is, by region, the A and C, and in Asia, always between regions, groups vps hosting C and E 61 . Although the genetic variability within a group do not appear to affect, significantly, the pathogenicity or the disease progression, it still poses serious problems for the development of a vaccine effective all groups and strains of HIV, for measurements of viral load and in some special cases of HIV test 62 . In the latter case, as well as testing based on the antigens of HIV-1 subtype B and HIV-2 subtype A, may have a lower sensitivity for the recognition of other sub- types, particularly during primary infection or infection with variants such as HIV-1 group O 63 . Origin of variability  The emergence of new genetic variants is due to a process of evolution , whose mechanisms are similar to those that explain the evolution of all living species. The only difference is affiliate marketing ebook that the evolution of HIV is extremely fast, which led to the large number of variants present. It explains the high genetic variability of HIV by several causes: Random mutations frequently In HIV, the rate of mutations is very important: more than a thousand times greater than in the genome of a human. Here’s why: the reverse transcriptase – that enables HIV to replicate – is an enzyme with no mechanism for detecting transcription errors. Errors are common and have been estimated at one every 1 700 to 10 000 nucleotides products. As the HIV genome consists of just under 10 000 nucleotides, there are approximately one and 10 mutations in each viral life cycle 64 , 65 , 66 , 67 , 68 . the large number of virions produced, which is the Plastic Containers order of 10,000 per day for each virion infecting a cell 64 . Within the whole body, every two days, 10 9 10 10 virions are renewed 65 . In theory, we can provide that each of these new virions is different mutations. Thus, in a single infected organism, there are already several genetic variants, representing a quasi-viral species . The variability of hcg diet the viral genome is not the same for all genes, some are more likely to change than others. Thus the gene env is the most variable (it is precisely that encodes surface proteins gp41 and gp120), whereas the gene pol is the most conserved 69 . Genetic recombination When a cell is infected with two genetically different virions, sequences can recombine , giving rise to recombinant forms. This process, random, is favored by risk behavior, because they increase the probability of multiple infections in one person. Selection denver martial arts Then there is a process of natural selection . Transcription errors and recombination produce many virions different from each other. Most of these mutations cause the production of virions unable to replicate properly, which are destined to disappear. This significant loss of virions is offset by the large number of virions produced. Among the survivors virions, some peculiarity of being more resistant to attack by immune system. This has the effect of making them better adapted to their environment and, ultimately, only the resistant virions are present in the body. This leads to more or less short term, an inefficient immune system, causing the state immunocompromised body if the rate of CD4 + lymphocytes is too low. The taking of medication by patients with HIV infection also leads to selection in the viral population. This favors the transmission of virions mutants most resistant to drugs. To counter this adaptation of HIV, HAART are designed to “attack” HIV facets of several at a time, and thus limit the possibility of the virus to adapt to its environment. Multiple origins The multiple time passages VIS CPZ to humans is the reason for the existence of different groups of HIV-1. It is the same for HIV-2, whose ancestor is the VIS mms . Diagnosis and monitoring of infection

Main article: HIV test . Early diagnosis of HIV infection is important for proper management of HIV / AIDS. In France , for example, one out of two is detected at the AIDS stage, which, in cases not detected by sixteen multiplies the risk of patient death within the first six months of treatment 70 . In developed countries, tests are performed routinely for blood donation , of organs and semen . The lack of contamination tests resulted in several mass 71 . The diagnosis HIV is a medical procedure performed in France by a doctor. Diagnosis  Diagnosis to determine the status of HIV HIV is made ​​in two steps: The screening , which in the reference method, involves detection of HIV antibodies confirmation that the antibodies detected are associated with HIV infection The first step is based on the detection of antibodies produced in response auctions online to infection with HIV, the HIV antibody. The production of antibodies can be detected with current means, on average 22 days after infection 72 . During this period, called the window period, the patient is completely infectious, posing obvious problems of public health . Once past the window period, HIV status can be established. The first step uses the method of detection ELISA , which uses antibody-antigen reaction to detect the presence of HIV antibodies. To avoid false negatives – that would miss an HIV cases – the test must have a sensitivity maximum. A mixture of antigens virus is then used, allowing the detection of antibodies to HIV-1 and HIV-2 (this is called a mixed ELISA). The use of two commercial tests of different origins is usually performed to remove the maximum amount of false positives from the first stage. If the detection is positive, doubtful or discordant 73 , confirmation is made. This is whether the antibodies detected are associated with HIV-1. For this, we use a method specifically , the aim is to eliminate false positives. This Bankruptcy is the method western blot (WB) which is generally used. Again, if the test is inconclusive or indicates an early seroconversion, a second confirmatory test is performed three weeks later, the time of seroconversion is complete. Only after all these tests that a doctor may declare an HIV patient. Other methods  There are other techniques for detection of HIV infection 74 , as: the rapid test, for example, the test INSTI HIV , which detects antibodies to HIV-1/HIV-2 in a minute of blood taken from the fingertip 75 p24 antigen: useful when seroconversion has not yet been completely: it is between J10 and J20 positivization after counting. The test becomes negative after seroconversion performed, so that explains the use of the procedure previously described as a standard the combined method: using p24 antigen and antibody detection. This method is useful in the early stages of contamination, because it reduces the window period to two to five days, while ensuring the inclusion of persons fully seroconverted isolation in culture: used for infants of HIV-positive mothers, because they are necessarily positive locksmiths (within the meaning of the term immunological, antibodies of the mother having been sent). The infection is confirmed if a reverse transcriptase activity is detected, or p24 antigen. detection of viral RNA: one seeks the genes gag and pol of HIV. This method tends to replace the method of culture isolation for newborns Follow infection  Once HIV infection is established, regular monitoring of the infection should be performed to ensure proper management of the disease and to better assess the patient’s condition. Two factors are considered: casino the rate of T cells 4 Chicago Criminal Lawyer , to define the level of infection viral load, indicating the number of virions in the body and, consequently, the rate of HIV replication in the body, helping to predict the evolution of infection The rate of T lymphocytes 4 measures the immune deficiency caused by the presence of HIV. This count is the number of T cells 4 in the blood. A normal rate in humans is between 600 and 1 200 T 4 / mm 3 . It is considered that 76  : to 500/mm 3 , the patient can live in normal conditions and does not require treatment from 350/mm 3 , antiviral treatment is recommended, the expected result is the decrease in viral load to the rise in the rate of T 4 below 200/mm 3 is highly immunocompromised patients and a significant risk to suffer from multiple opportunistic infections associated with AIDS. Antiviral treatment and an antibiotic is therefore essential to avoid these complications. The difference between two measurements of viral load over time intervals used to evaluate the rate of HIV San Diego Homes For Rent replication and, consequently, the progression of infection. There is a direct relationship between viral load and the level of immune deficiency, caused mainly by the disappearance of T cells 4 . Viral load is defined by measuring the concentration of viral RNA in the blood. This may vary greatly depending on the methods used and for this reason, it is important that all assessments of viral load to be carried out in the same laboratory using the same technique 77 . This is the log 10 copy number / mL which is used to assess the variation in time of viral load. A change greater than or equal to 0.5 is significant 77 . It is the combination of these two pieces of information that allows the physician to determine the patient’s treatment. Pathophysiology

 

The evolution of HIV infection is called persistent productive and is represented by the diagram showing the relationship between viral load and the number of T cells 4 .       Number of T cells 4 per mm 3 of plasma       Number of copies of viral RNA per ml of plasma The HIV infection evolves in several phases that can succeed in time: with primary infection (50 to 75% of cases) or without symptoms of seroconversion phase after the contamination; a lag phase, perhaps with a state of generalized lymphadenopathy; one phase to minor cna certification symptoms of infection with human immunodeficiency virus; the phase of profound immunosuppression, or generally symptomatic stage of AIDS. Upon primary infection, the virus replicates actively in the body, with a daily output of ten billion virions, resulting in the destruction of approximately five billion CD4 + T cells 78 . This replication stabilizes after a roadrage few weeks, at a more or less important depending on the subject. The immune system, hyperactive, partially offsets the massive destruction of CD4 + T cells by increasing production, but HIV infection still persists, resulting in the emergence and selection of virus mutants that escape the immune response of the host. Researchers from the CNRS, the Institut Curie and Institut Pasteur discovered that the virus changed the pH of cellular compartments where it accumulates in macrophages, thus preventing the activation of enzymes responsible for degrading it 79 . For several years, the CD4 + T cells appear to be repeated rapidly despite their destruction by the virus, until the exhaustion of central lymphoid organs ( thymus ) was no longer regeneration. The destruction of CD4 + T cells is often due to the hyperactivation of these cells by interacting with certain structures of the virus, not a direct destruction by HIV 78 . After ten to fifteen years of evolution without treatment, the subject is immunocompromised (stage AIDS ), the infectious diseases or tumor rare (say opportunistic ) occur and lead to death. Currently treatments antiretroviral prevent or delay progression to AIDS stage, maintaining the levels of virus replication at the lowest possible 78 . The destruction of the immune system and clinical progression with the appearance of opportunistic diseases are directly related to blood levels of CD4 + T cells from patient 80 . The effectiveness of antiretroviral treatment is evaluated by the level of viral replication as measured by HIV viral load (plasma RNA), the measurement of rate of CD4 + T cells (immunosuppression) and the patient’s clinical status. Non-progressors, long-term  Main article: Asymptomatic long-term . Several cases of HIV positive people have managed to keep for a long time (at least 8 years), of course (that is, without treatment), a normal CD4 count (greater than 500/mm ³) and a low viral load or even undetectable in some 81 , 82 . They are called non-progressors, long-term or long-term asymptomatic (ALT). Some French patients remained asymptomatic without treatment, and pikalaina even almost undetectable viral load for at least twenty years 83 . There is no single model, some patients remain weight loss pills asymptomatic in a state with no significant change in their condition, others (the majority) have a slow deterioration of their immune system. Note the important role of mitochondria in the evolution of more or less rapid deterioration of viral replication and the decrease of the immune response. Protection of mitochondria slows the decline in T cells and CD4 life insurance quotes and viral replication, promoting the state “ALT” . Regular intake of co-enzymes Q1O (> 100 mg / d) associated with various antioxidants vitamins A , B , C , D , E , K , and taking different minerals antioxidants have a protective effect these mitochondria during mitochondrial impairment diseases, which promotes a good immune response. This protective role is also important when taking antiretroviral therapy, by blocking some of the inherent toxicity of taking the remedy and activating the anti-oxidation 84 . It is important to note that one or more re-infections with other types or subtypes of HIV strains is not conducive to maintaining the state “ALT” because, due to the rapid mutation of HIV The risk of genetic recombination (in terms of mathematical probability) with more virulent strains necessarily decreases the immune resistance of a patient’s immune response and lambda against future antiretroviral treatment. HIV controllers  Main article: Control of HIV . Some patients are very rare (less than 1%), which do not develop disease despite sometimes more than twenty years of HIV infection and in the absence of treatment, are known as “HIV controllers” (HIC). These patients infected with HIV do not develop AIDS , which the body naturally and sustainably managed to control viral replication, the virus now almost undetectable in the plasma (to less than 50 copies of viral RNA / ml) 85 , 86 . They are the subject of research that could lead to drugs or a vaccine against HIV 87 . Epidemiology

 

Prevalence of HIV carriers in the world (2008).

Statistics of infections and deaths between 1990 and 2008. Worldwide, each year there are approximately 2.5 million new infections. In 2007, there were 33.2 million people living with human immunodeficiency virus, the majority in sub-Saharan Africa. The same year, 2.1 million died of AIDS were identified 88 . In France , for the year 2005 , the Institut de Veille Sanitaire estimated that about 6700 new cases of HIV infection (stable since 2003). Heterosexual intercourse accounts for half of new cases and relate to half of sub-Saharan Africa. Between 2003 and 2005, the number of new seropositive decreased in women but increased among gay men who represent 27% of new infections. The proportion of HIV-2 infections was 1.4% in 2005. Among the HIV-1 infection, the proportion of non-subtype B decreased between 2003 and 2005 (from 50% to 41%). In 2005, 5.3 million HIV status were performed, an increase of 8% over 2004, while the number of confirmed positive serology stabilized 89 . Treatments

The ARV is the therapeutic arsenal against HIV, which is expanding gradually. Twenty antiretroviral drugs are available in 2006 and intended to interfere different mechanisms: first, the enzymes necessary for HIV replication and, secondly, its mechanisms of cell entry. Thanks to the triple therapy used since 1996 , the mortality due to AIDS has dropped significantly, wherever these new treatments were available 90 , 91 , 92 , 93 . Thus the United States, the widespread use of HAART has increased the number of deaths each year from 49,000 in 1995 to about 9000 in 2001 94 . These drugs can have side effects temporary or permanent, which can lead to discontinuation or modification of the above treatment, knowing that, if properly followed, they have a relatively high efficiency. Antiretrovirals  Main article: Antiretroviral . Research on HIV / AIDS is very important, many research studies and publications are regularly updated. But the time between the conception of a molecule and its authorization for the market of between seven and twelve years in France 95 , it is relative effects of ads that, for some, will not lead to a direct application in practice the fight against HIV / AIDS. Thus the only really effective drugs known as antiretrovirals are receiving their authorization on the market. Antiretroviral drugs are classified according to their field of action: Reverse transcriptase inhibitors  Main article: reverse transcriptase inhibitors . The reverse transcriptase inhibitors prevent the synthesis of proviral DNA (that is to say that will allow replication of the virus) from the viral RNA. Found in this class: Nucleoside (NRTI) The NRTIs were the first class of antiretroviral drugs on the market in 1985 . They include zidovudine (AZT) (synthesized in 1964 ), the didanosine (ddI), the zalcitabine (ddC), the stavudine (d4T), the lamivudine (3TC) ( in 1989 and used from 1995 ), the abacavir ( ABC) and the emtricitabine (FTC). Mutations in the genome because of the HIV reverse transcriptase confer resistance to NRTIs, which fender flares can be cross several NRTIs. These compounds are neutral or reducing, with the exception of AZT, which is an oxidant. Non-nucleoside inhibitors (NNRTIs) The NNRTIs are potent inhibitors and highly selective HIV reverse transcriptase. Found in this class of nevirapine and the efavirenz . They are only active on HIV-1. They are metabolized to phenols by oxidation. Nucleotide analogues The nucleotide analogues such as tenofovir , which was marketed in 2002 , are organophosphates. Protease inhibitors  Main article: Protease Inhibitors . The class of protease inhibitors (PI) is a class of antiretroviral drugs on the market in 1996 . It was a major turning point in therapeutic strategies against the human immunodeficiency virus. They act Judaica Bat Mitzvah Gifts by inhibiting the action of the viral protease, which allows the cutting and assembly of viral proteins, a Phen375 Reviews process essential to the production of infectious virus. This gives the virions unable to infect new cells. NPs are active on HIV-1 and HIV-2, and do not create cross-resistance with NRTIs or NNRTIs. Integrase inhibitors  Main article: integrase inhibitors . These inhibitors block the action of integrase, thus preventing the viral genome to bind to the target cell. A single molecule is currently available: the Raltegravir , sold under the brand name Isentress. The elvitegravir and dolutégravir are currently in clinical trials of phase III . Fusion inhibitors  Main article: fusion inhibitor . Fusion inhibitors-analysis carried out before the replication cycle of HIV by blocking the surface proteins of HIV or disrupting the co-receptor cells targeted by HIV. Several products are under consideration and in 2009 , only the enfuvirtide and maraviroc have received permission to market . Therapeutic choice  Since the early 1990s, various combination therapies have emerged, as may be prescribed depending on clinical stage, the rate of lymphocytes T CD4 + and viral load . It currently consists of three antiretroviral drugs, usually two nucleoside reverse transcriptase associated with a protease inhibitor or a non-nucleoside reverse transcriptase inhibitors, or sometimes a third nucleoside reverse transcriptase inhibitors (HAART). A fusion inhibitor is possibly associated. There are no precise criteria for all patients setting the start of antiretroviral therapy: the decision must be individualized for each patient. There are still some criteria based on the number of CD4 + T cells. Thus, when HIV has a CD4 + cell count greater than 350/mm 3 , it is not necessary to start treatment. But below 200/mm pro flight simulator 3 , it is imperative to begin treatment. CD4 counts compared to the total number of lymphocytes is also a criterion. Thus, when the CD4 + less than 15% of all lymphocytes, a risk of infection by opportunistic diseases is 96 . In a first treatment, almost all patients engagement ring see their rendered undetectable plasma viral load in the first six months. The first treatment should be as simple as possible and better tolerated. This is the cash advance online non observance of the treatment is the main cause of treatment failure 97 . Although antiretroviral therapy are very effective when properly followed, HIV is still present in the body. Only its multiplication is slowed and although undetectable in the blood, the latter, and the sperm remain infectious 98 . Prevention

Although research is very active and that some candidates vaccines exist for one with encouraging results regarding the feasibility of developing a vaccine 99 , there are none really effective against this virus. Only condoms offer effective protection during sex. Blood donations are subject to a selection of donors, systematic screening and treatment specific. Therefore, prevention is the use of disposable syringes for any occasion, especially if drug intravenously or replacement therapy. Despite the wide dissemination of information about the disease and prevention, some people still risk behaviors (see article AIDS risk-taking ), which requires the actions of prevention . Post-exposure

The post-exposure treatment (PET) is currently the only way to stop HIV, or rather, not to be contaminated with the virus after exposure. Indeed, following exposure to a risk of infection (unprotected sex, for example), no later than 48 hours of the exhibition, if the treatment is taken, the risk of becoming infected is reduced 80%, making it a relatively effective. The scientific community agrees that this is not enough to be sure of not contracting the virus. In addition, problems of intolerance to these drugs make these treatments are not always taken as long as necessary (1 month). Also, the use of condoms is still recommended, as the only effective means of protection if used correctly . Challenging the link with AIDS

Main article: Challenging the responsibility of HIV in AIDS . Some individuals or groups are questioning the causal link between HIV and AIDS, or deny the existence of the virus 100 , 101 . Virologist Peter Duesberg claims that AIDS is caused by the long-term consumption of drugs or ARVs. This view was taken for a time by the Government of South Africa and, more particularly, its then president, Thabo Mbeki . In response to these controversies, the Durban Declaration notes that the evidence that AIDS is caused by HIV are clear, unambiguous and consistent with the highest standards of science 102 . These challenges are, according to the general point of view, a threat to public health by discouraging people from being tested or the patients being under antiretroviral treatment that have proven 103 , 104 . These dissenters argue that the official approach to AIDS, which takes for granted the causal retroviral resulted in misdiagnosis, the development of psychological terror and some form of racism, the use of toxic treatments and waste of public funds 105 , 106 . These web hosting review views are widely rejected 107 , 108 and are considered the pseudo-science by most members of the scientific community.