|Human immunodeficiency viruses|
|Scanning electron micrograph of HIV-1 (in green) budding from cultured lymphocyte. Multiple round bumps on cell surface represent sites of assembly and budding of virions.|
|Cladistically included but traditionally excluded taxa|
The human immunodeficiency viruses (HIV) are two species of Lentivirus (a subgroup of retrovirus) that causes HIV infection and over time acquired immunodeficiency syndrome (AIDS). AIDS is a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, 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 is present as both free virus particles and virus within infected immune cells.
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 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 the development of AIDS.
|HIV-2||Lower||Low||West Africa||Sooty mangabey|
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 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, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system, for an indiscriminate amount of time. The HIV 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 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 is largely confined to West Africa.
HIV is different in structure from other retroviruses. It is roughly spherical with a diameter of about 120 nm, around 60 times smaller than a red blood cell. It is composed of two copies of positive-sense single-stranded RNA that codes for the virus's nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24. The single-stranded RNA 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 the advent of AIDS. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be 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 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 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 the target cell surface. Gp120 binds to integrin α4β7 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 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 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 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 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 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 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 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-κB (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, the integrated DNA provirus is transcribed into RNA, some of which then undergo RNA splicing to produce mature messenger RNAs (mRNAs). These mRNAs are exported from the nucleus into the cytoplasm, where they are translated into the regulatory proteins Tat (which encourages new virus production) and 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 new copies of the virus genome, while others function as mRNAs that are translated to produce the structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles.
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 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 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 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 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, 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 damages, including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defensive strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses is an adaptation for repair of genome damages, 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 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 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 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 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 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 the HIV virological synapse in vivo. The many spreading 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 1010 virions every day, coupled with a high mutation rate of approximately 3 x 10−5 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase.
This complex scenario leads to 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, 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 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), 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 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 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 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 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, 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 is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or receive 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 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, 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.
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, 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 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.
The latest recommendations of the US Centers for Disease Control and Prevention (CDC) show that HIV testing must start with an immunoassay combination test for HIV-1 and HIV-2 antibodies and p24 antigen. A negative result rules out HIV exposure, while a positive one must be followed by an HIV-1/2 antibody differentiation immunoassay to detect which antibodies are present. This gives rise to four possible scenarios:
HIV/AIDS research includes all medical research that attempts to prevent, treat, or cure HIV/AIDS, as well as fundamental research about the nature of HIV as an infectious agent and AIDS as the disease caused by HIV.
Many governments and research institutions participate in HIV/AIDS research. This research includes behavioral health interventions, such as research into sex education, and drug development, such as research into microbicides for sexually transmitted diseases, HIV vaccines, and anti-retroviral drugs. Other medical research areas include the topics of pre-exposure prophylaxis, post-exposure prophylaxis, circumcision and HIV, and accelerated aging effects.
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs. In many parts of the world, HIV has become a chronic condition in which progression to AIDS is increasingly rare.
HIV latency, and the consequent viral reservoir in CD4+ T cells, dendritic cells, as well as macrophages, is the main barrier to eradication of the virus.
It is important to note that although HIV is highly virulent, transmission does not occur through sex when an HIV-positive person has a consistently undetectable viral load (<50 copies/ml) due to anti-retroviral treatment. Previously it was said the chance of transmission was 'very low' or 'negligable' (The 'Swiss Statement'). However, following multiple studies its is now clear that the chance of passing on HIV through sex is zero where the HIV-positive person has a consistently undetectable viral load, this is known as 'U=U' or 'Undetectable=Untransmittable', also phrased as 'can't pass it on'. The studies demonstrating U=U are; Opposites Attract, PARTNER 1, PARTNER 2, and HPTN052. In these studies couples where one partner was HIV positive and one partner was HIV negative were enrolled and regular HIV testing completed. In total from the four studies, 4097 couples were enrolled over four continents and 151,880 acts of condomless sex were reported, there were zero phylogenetically linked transmissions of HIV where the positive partner had an undetecable viral load. Following this the U=U consensus statement advocating the use of 'zero risk' was signed by hundreds of individuals and organisations including the US CDC, British HIV Association and The Lancet medical journal.
AIDS was first clinically observed in 1981 in the United States. The initial cases were a cluster of injection drug users and gay men with no known cause of impaired immunity who showed symptoms of Pneumocystis jirovecii pneumonia (PJP), a rare opportunistic infection that was known to occur in people with very compromised immune systems. Soon thereafter, additional gay men developed a previously rare skin cancer called Kaposi's sarcoma (KS). Many more cases of PJP and KS emerged, alerting U.S. Centers for Disease Control and Prevention (CDC) and a CDC task force was formed to monitor the outbreak. The earliest retrospectively described case of AIDS is believed to have been in Norway beginning in 1966.
In the beginning, the CDC did not have an official name for the disease, often referring to it by way of the diseases that were associated with it, for example, lymphadenopathy, the disease after which the discoverers of HIV originally named the virus. They also used Kaposi's Sarcoma and Opportunistic Infections, the name by which a task force had been set up in 1981. In the general press, the term GRID, which stood for gay-related immune deficiency, had been coined. The CDC, in search of a name, and looking at the infected communities coined "the 4H disease", as it seemed to single out homosexuals, heroin users, hemophiliacs, and Haitians. However, after determining that AIDS was not isolated to the gay community, it was realized that the term GRID was misleading and AIDS was introduced at a meeting in July 1982. By September 1982 the CDC started using the name AIDS.
In 1983, two separate research groups led by American Robert Gallo and French investigators Françoise Barré-Sinoussi and Luc Montagnier independently declared that a novel retrovirus may have been infecting AIDS patients, and published their findings in the same issue of the journal Science. Gallo claimed that a virus his group had isolated from a person with AIDS was strikingly similar in shape to other human T-lymphotropic viruses (HTLVs) his group had been the first to isolate. Gallo's group called their newly isolated virus HTLV-III. At the same time, Montagnier's group isolated a virus from a patient presenting with swelling of the lymph nodes of the neck and physical weakness, two classic symptoms of primary HIV infection. Contradicting the report from Gallo's group, Montagnier and his colleagues showed that core proteins of this virus were immunologically different from those of HTLV-I. Montagnier's group named their isolated virus lymphadenopathy-associated virus (LAV). As these two viruses turned out to be the same, in 1986 LAV and HTLV-III were renamed HIV.
Another group working contemporaneously with the Montagnier and Gallo groups was that of Dr. Jay Levy at the University of California, San Francisco. He independently discovered the AIDS virus in 1983 and named it the AIDS associated retrovirus (ARV). This virus was very different from the virus reported by the Montagnier and Gallo groups. The ARV strains indicated, for the first time, the heterogeneity of HIV isolates and several of these remain classic examples of the AIDS virus found in the United States.
Both HIV-1 and HIV-2 are believed to have originated in non-human primates in West-central Africa, and are believed to have transferred to humans (a process known as zoonosis) in the early 20th century.
HIV-1 appears to have originated in southern Cameroon through the evolution of SIVcpz, a simian immunodeficiency virus (SIV) that infects wild chimpanzees (HIV-1 descends from the SIVcpz endemic in the chimpanzee subspecies Pan troglodytes troglodytes). The closest relative of HIV-2 is SIVsmm, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in littoral West Africa (from southern Senegal to western Côte d'Ivoire). New World monkeys such as the owl monkey are resistant to HIV-1 infection, possibly because of a genomic fusion of two viral resistance genes.
HIV-1 is thought to have jumped the species barrier on at least three separate occasions, giving rise to the three groups of the virus, M, N, and O.
There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV. However, SIV is a weak virus, and it is typically suppressed by the human immune system within weeks of infection. It is thought that several transmissions of the virus from individual to individual in quick succession are necessary to allow it enough time to mutate into HIV. Furthermore, due to its relatively low person-to-person transmission rate, it can only spread throughout the population in the presence of one or more high-risk transmission channels, which are thought to have been absent in Africa prior to the 20th century.
Specific proposed high-risk transmission channels, allowing the virus to adapt to humans and spread throughout the society, depend on the proposed timing of the animal-to-human crossing. Genetic studies of the virus suggest that the most recent common ancestor of the HIV-1 M group dates back to circa 1910. Proponents of this dating link the HIV epidemic with the emergence of colonialism and growth of large colonial African cities, leading to social changes, including different patterns of sexual contact (especially multiple, concurrent partnerships), the spread of prostitution, and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities. While transmission rates of HIV during vaginal intercourse are typically low, they are increased manyfold if one of the partners suffers from a sexually transmitted infection resulting in genital ulcers. Early 1900s colonial cities were notable due to their high prevalence of prostitution and genital ulcers to the degree that as of 1928 as many as 45% of female residents of eastern Leopoldville were thought to have been prostitutes and as of 1933 around 15% of all residents of the same city were infected by one of the forms of syphilis.
An alternative view—unsupported by evidence—holds that unsafe medical practices in Africa during years following World War II, such as unsterile reuse of single-use syringes during mass vaccination, antibiotic, and anti-malaria treatment campaigns, were the initial vector that allowed the virus to adapt to humans and spread.
The earliest, well-documented case of HIV in a human dates back to 1959 in the Belgian Congo. The virus may have been present in the United States as early as the mid-to-late 1950s, as a sixteen-year-old male presented with symptoms in 1966 and died in 1969.
Dr. Marx believes that the crucial event was the introduction into Africa of millions of inexpensive, mass-produced syringes in the 1950s. ... suspect that the growth of colonial cities is to blame. Before 1910, no Central African town had more than 10,000 people. But urban migration rose, increasing sexual contacts and leading to red-light districts.
In molecular biology, CD4 (cluster of differentiation 4) is a glycoprotein found on the surface of immune cells such as T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 (after the OKT4 monoclonal antibody that reacted with it) before being named CD4 in 1984. In humans, the CD4 protein is encoded by the CD4 gene.CD4+ T helper cells are white blood cells that are an essential part of the human immune system. They are often referred to as CD4 cells, T-helper cells or T4 cells. They are called helper cells because one of their main roles is to send signals to other types of immune cells, including CD8 killer cells, which then destroy the infectious particle. If CD4 cells become depleted, for example in untreated HIV infection, or following immune suppression prior to a transplant, the body is left vulnerable to a wide range of infections that it would otherwise have been able to fight.Charlie Sheen
Carlos Irwin Estévez (born September 3, 1965), known professionally as Charlie Sheen, is an American actor. Sheen has appeared in films including Platoon (1986), Wall Street (1987), Young Guns (1988), Eight Men Out (1988), Major League (1989), Hot Shots! (1991), and The Three Musketeers (1993).
In the 2000s, Sheen replaced Michael J. Fox in Spin City, his performance earning him a Golden Globe Award for Best Actor – Television Series Musical or Comedy. He then starred in Two and a Half Men which earned him several Golden Globe and Emmy Award nominations. He most recently starred in the FX comedy series Anger Management, which concluded its 100-episode run in 2014. In 2010, Sheen was the highest paid actor on television and earned US$1.8 million per episode of Two and a Half Men.Sheen's personal life has made headlines, including reports of alcohol and drug abuse and marital problems, as well as allegations of domestic violence. In March 2011, his contract for Two and a Half Men was terminated by CBS and Warner Bros following his derogatory comments about the series' creator, Chuck Lorre. On November 17, 2015, Sheen publicly revealed that he is HIV positive, having been diagnosed about four years earlier.Circumcision
Circumcision is the removal of the foreskin from the human penis. In the most common procedure, the foreskin is opened, adhesions are removed, and the foreskin is separated from the glans. After that, a circumcision device may be placed and then the foreskin is cut off. Topical or locally injected anesthesia is sometimes used to reduce pain and physiologic stress. For adults and children, general anesthesia is an option, and the procedure may be performed without a specialized circumcision device. The procedure is most often an elective surgery performed on babies and children for religious or cultural reasons. In other cases it may be done as a treatment for certain medical conditions or for preventative reasons. Medically it is a treatment option for problematic cases of phimosis, balanoposthitis that does not resolve with other treatments, and chronic urinary tract infections (UTIs). It is contraindicated in cases of certain genital structure abnormalities or poor general health.The positions of the world's major medical organizations range from considering elective circumcision of babies and children as having no benefit and significant risks, to it having a modest health benefit that outweighs small risks. No major medical organization recommends either universal circumcision of all males or banning the procedure. Ethical and legal questions regarding informed consent and human rights have been raised over the circumcision of babies and children for non-medical reasons; for these reasons the procedure is controversial.Male circumcision reduces the risk of HIV infection among heterosexual men in sub-Saharan Africa. Consequently the WHO recommends considering circumcision as part of a comprehensive HIV prevention program in areas with high rates of HIV such as sub-Saharan Africa. There is also some evidence for circumcision reducing HIV infection risk for men who have sex with men. The effectiveness of using circumcision to prevent HIV in the developed world is unclear. Circumcision is associated with reduced rates of cancer-causing forms of human papillomavirus (HPV), UTIs, and cancer of the penis. Prevention of those conditions is not a justification for routine circumcision of infants. Studies of other sexually transmitted infections are suggestive that circumcision is protective. A 2010 review found circumcisions performed by medical providers to have a typical complication rate of 1.5% for babies and 6% for older children, with few cases of severe complications. Bleeding, infection, and the removal of either too much or too little foreskin are the most common complications cited. Complication rates are higher when the procedure is performed by an inexperienced operator, in unsterile conditions, or in older children. Circumcision does not appear to have a negative impact on sexual function.An estimated one-third of males worldwide are circumcised. The procedure is most common among Muslims and Jews (where it is near-universal for religious reasons), and in the United States and parts of Southeast Asia and Africa. It is relatively rare for non-religious reasons in Europe, Latin America, parts of Southern Africa, and most of Asia. The origin of circumcision is not known with certainty; the oldest documented evidence for it comes from ancient Egypt. Various theories have been proposed as to its origin including as a religious sacrifice and as a rite of passage marking a boy's entrance into adulthood. It is part of religious law in Judaism and is an established practice in Islam, Coptic Christianity, and the Ethiopian Orthodox Church. The word circumcision is from Latin circumcidere, meaning "to cut around".Discrimination against people with HIV/AIDS
Discrimination against people with HIV/AIDS or serophobia is the prejudice, fear, rejection and discrimination against people living with HIV/AIDS (PLHIV). Discrimination is one manifestation of stigma, and stigmatizing attitudes and behaviors may fall under the rubric of discrimination depending on the legislation of a particular country. HIV stands for human immunodeficiency virus. If left untreated, HIV can lead to the disease AIDS (acquired immunodeficiency syndrome). HIV/AIDS is a sexually transmitted disease and cannot be cured, but with proper treatment, the individual can live just as long as without the disease.
HIV/AIDS discrimination exists around the world, including ostracism, rejection, discrimination, and avoidance. Consequences of stigma and discrimination against PLHIV may result in low turn-out for HIV counselling and testing, identity crises, isolation, loneliness, low self-esteem and lack of interest in containing the disease.Much HIV/AIDS stigma or discrimination involves homosexuality, bisexuality, promiscuity, sex workers, and intravenous drug use.
In many developed countries, a strong correlation exists between HIV/AIDS and male homosexuality or bisexuality (the CDC states, "Gay, bisexual, and other men who have sex with men (MSM) represent approximately 2% of the United States population, yet are the population most severely affected by HIV"), and association is correlated with higher levels of sexual prejudice such as homophobic attitudes. An early name for AIDS was gay-related immune deficiency or GRID. During the early 1980s, HIV/AIDS was "a disorder that appears to affect primarily male homosexuals".Some forms of serious discrimination can include: being excluded from consideration for a job, being prohibited from buying a house, needing to pay extra money when renting housing, compulsory HIV testing without prior consent or protection of confidentiality; the quarantine of HIV infected individuals and, in some cases, the loss of property rights when a spouse dies. HIV testing without permission or security may also be considered as wrongdoings against those with HIV. The United States' disability laws prohibit HIV/AIDS discrimination in housing, employment, education, and access to health and social services. The U.S. Department of Housing and Urban Development Office of Fair Housing and Equal Opportunity enforces laws prohibiting housing discrimination based on actual or perceived HIV/AIDS status.HIV/AIDS
Human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV). Following initial infection, a person may not notice any symptoms or may experience a brief period of influenza-like illness. Typically, this is followed by a prolonged period with no symptoms. As the infection progresses, it interferes more with the immune system, increasing the risk of developing common infections such as tuberculosis, as well as other opportunistic infections, and tumors that rarely affect people who have uncompromised immune systems. These late symptoms of infection are referred to as acquired immunodeficiency syndrome (AIDS). This stage is often also associated with unintended weight loss.HIV is spread primarily by unprotected sex (including anal and oral sex), contaminated blood transfusions, hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Methods of prevention include safe sex, needle exchange programs, treating those who are infected, pre- and post-exposure prophylaxis, and male circumcision. Disease in a baby can often be prevented by giving both the mother and child antiretroviral medication. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. Treatment is recommended as soon as the diagnosis is made. Without treatment, the average survival time after infection is 11 years.In 2016, about 36.7 million people were living with HIV and it resulted in 1 million deaths. There were 300,000 fewer new HIV cases in 2016 than in 2015. Most of those infected live in sub-Saharan Africa. From the time AIDS was identified in the early 1980s to 2017, the disease has caused an estimated 35 million deaths worldwide. HIV/AIDS is considered a pandemic—a disease outbreak which is present over a large area and is actively spreading. HIV originated in west-central Africa during the late 19th or early 20th century. AIDS was first recognized by the United States Centers for Disease Control and Prevention (CDC) in 1981 and its cause—HIV infection—was identified in the early part of the decade.HIV/AIDS has had a large impact on society, both as an illness and as a source of discrimination. The disease also has large economic impacts. There are many misconceptions about HIV/AIDS such as the belief that it can be transmitted by casual non-sexual contact. The disease has become subject to many controversies involving religion including the Catholic Church's position not to support condom use as prevention. It has attracted international medical and political attention as well as large-scale funding since it was identified in the 1980s.HIV/AIDS denialism
HIV/AIDS denialism is the belief, contradicted by conclusive evidence, that human immunodeficiency virus (HIV) does not cause acquired immune deficiency syndrome (AIDS). Some of its proponents reject the existence of HIV, while others accept that HIV exists but argue that it is a harmless passenger virus and not the cause of AIDS. Insofar as they acknowledge AIDS as a real disease, they attribute it to some combination of sexual behavior, recreational drugs, malnutrition, poor sanitation, haemophilia, or the effects of the drugs used to treat HIV infection (antiretrovirals).The scientific consensus is that the evidence showing HIV to be the cause of AIDS is conclusive and that HIV/AIDS denialist claims are pseudoscience based on conspiracy theories, faulty reasoning, cherry picking, and misrepresentation of mainly outdated scientific data. With the rejection of these arguments by the scientific community, HIV/AIDS denialist material is now targeted at less scientifically sophisticated audiences and spread mainly through the Internet.Despite its lack of scientific acceptance, HIV/AIDS denialism has had a significant political impact, especially in South Africa under the presidency of Thabo Mbeki. Scientists and physicians have raised alarm at the human cost of HIV/AIDS denialism, which discourages HIV-positive people from using proven treatments. Public health researchers have attributed 330,000 to 340,000 AIDS-related deaths, along with 171,000 other HIV infections and 35,000 infant HIV infections, to the South African government's former embrace of HIV/AIDS denialism. The interrupted use of antiretroviral treatments is also a major global concern as it potentially increases the likelihood of the emergence of antiretroviral-resistant strains of the virus.HIV/AIDS in Africa
HIV/AIDS is a major public health concern and cause of death in many parts of Africa. Although the continent is home to about 15.2 percent of the world's population, more than two-thirds of the total infected worldwide – some 35 million people – were Africans, of whom 15 million have already died. Sub-Saharan Africa alone accounted for an estimated 69 percent of all people living with HIV and 70 percent of all AIDS deaths in 2011. In the countries of sub-Saharan Africa most affected, AIDS has raised death rates and lowered life expectancy among adults between the ages of 20 and 49 by about twenty years. Furthermore, the life expectancy in many parts of Africa is declining, largely as a result of the HIV/AIDS epidemic with life-expectancy in some countries reaching as low as thirty-four years.Countries in North Africa and the Horn of Africa have significantly lower prevalence rates, as their populations typically engage in fewer high-risk cultural patterns that have been implicated in the virus' spread in Sub-Saharan Africa. Southern Africa is the worst affected region on the continent. As of 2011, HIV has infected at least 10 percent of the population in Botswana, Lesotho, Malawi, Mozambique, Namibia, South Africa, Eswatini, Zambia, and Zimbabwe.In response, a number of initiatives have been launched in various parts of the continent to educate the public on HIV/AIDS. Among these are combination prevention programmes, considered to be the most effective initiative, such as the abstinence, be faithful, use a condom campaign and the Desmond Tutu HIV Foundation's outreach programs.According to a 2013 special report issued by the Joint United Nations Programme on HIV/AIDS (UNAIDS), the number of HIV positive people in Africa receiving anti-retroviral treatment in 2012 was over seven times the number receiving treatment in 2005, "with nearly 1 million added in the last year alone". The number of AIDS-related deaths in Sub-Saharan Africa in 2011 was 33 percent less than the number in 2005. The number of new HIV infections in Sub-Saharan Africa in 2011 was 25 percent less than the number in 2001.HIV/AIDS in the United States
The AIDS epidemic, caused by HIV (Human Immunodeficiency Virus), found its way to the United States as early as 1960, but was first noticed after doctors discovered clusters of Kaposi's sarcoma and pneumocystis pneumonia in young gay men in Los Angeles, New York City, and San Francisco in 1981. Treatment of HIV/AIDS is primarily via a "drug cocktail" of antiretroviral drugs, and education programs to help people avoid infection.
Initially, infected foreign nationals were turned back at the U.S. border to help prevent additional infections. The number of U.S. deaths from AIDS have declined sharply since the early years of the disease's presentation domestically. In the United States, 1.2 million people live with an HIV infection, of whom 15% are unaware of their infection. Gay and bisexual men, African Americans, and Latinos remain disproportionately affected by HIV/AIDS in the U.S.History of HIV/AIDS
AIDS is caused by a human immunodeficiency virus (HIV), which originated in non-human primates in Central and West Africa. While various sub-groups of the virus acquired human infectivity at different times, the global pandemic had its origins in the emergence of one specific strain – HIV-1 subgroup M – in Léopoldville in the Belgian Congo (now Kinshasa in the Democratic Republic of the Congo) in the 1920s.There are two types of HIV: HIV-1 and HIV-2.
HIV-1 is more virulent, is more easily transmitted and is the cause of the vast majority of HIV infections globally. The pandemic strain of HIV-1 is closely related to a virus found in chimpanzees of the subspecies Pan troglodytes troglodytes, which live in the forests of the Central African nations of Cameroon, Equatorial Guinea, Gabon, Republic of Congo (or Congo-Brazzaville), and Central African Republic.
HIV-2 is less transmittable and is largely confined to West Africa, along with its closest relative, a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey inhabiting southern Senegal, Guinea-Bissau, Guinea, Sierra Leone, Liberia, and western Ivory Coast.Joint United Nations Programme on HIV/AIDS
The Joint United Nations Programme on HIV and AIDS (UNAIDS) is the main advocate for accelerated, comprehensive and coordinated global action on the HIV/AIDS pandemic.
The mission of UNAIDS is to lead, strengthen and support an expanded response to HIV and AIDS that includes preventing transmission of HIV, providing care and support to those already living with the virus, reducing the vulnerability of individuals and communities to HIV and alleviating the impact of the epidemic. UNAIDS seeks to prevent the HIV/AIDS epidemic from becoming a severe pandemic.
UNAIDS has five goals:
Leadership and advocacy for effective action on the pandemic;
Strategic information and technical support to guide efforts against AIDS worldwide;
Tracking, monitoring and evaluation of the pandemic and of responses to it;
Civil society engagement and the development of strategic partnerships;
Mobilization of resources to support an effective response.UNAIDS is headquartered in Geneva, Switzerland, where it shares some site facilities with the World Health Organization. It is a member of the United Nations Development Group. Its first executive director was Peter Piot; Michel Sidibé currently leads UNAIDS; however, he offered his resignation on 13 December 2018 following an expert report on sexual harassment in the agency that criticized his "defective leadership" and fostering a work environment that tolerated bullying and a culture of fear among the staff.The agency promotes the GIPA principle (greater involvement of people living with HIV) formulated in 1994, and endorsed by the United Nations in 2001 and 2006.List of countries by HIV/AIDS adult prevalence rate
The human immunodeficiency virus (HIV), which causes AIDS, varies in prevalence from nation to nation. Listed here are the prevalence rates among adults in various countries, based on data from various sources, largely the CIA World Factbook.
As of 2015, it is estimated that there are 36.7 million people worldwide infected with HIV.The HIV pandemic is most severe in Southern Africa. Over 10% of all people living with HIV/AIDS reside within the region. Adult HIV prevalence exceeds 20% in Eswatini (Swaziland), Botswana, and Lesotho, while an additional six countries report adult HIV prevalence of at least 10%. Outside Africa, the highest prevalence rate is found in the Bahamas (3.3%).In absolute numbers, South Africa (7.1 million), followed by Nigeria (3.2 million), and India (2.1 million) had the highest HIV/AIDS number of cases by the end of 2016. While South Africa's large population of HIV-positive people is attributable to its high disease prevalence (18.9%, one of the highest in the world), Nigeria's is lower at 2.9%, with India's prevalence rate at 0.3%.. However, countries such as Nigeria with high HIV rates above 1% are classified as having Generalized HIV Epidemics (GHEs) by UNAIDS, while India's prevalence is well below this threshold, with a prevalence lower than America's and about the same as France .
On the other end of the spectrum, Svalbard is reported as having no cases of HIV/AIDS, while Bhutan has a much larger population but still only an estimated 246 cases through 2011.Magic Johnson
Earvin "Magic" Johnson Jr. (born August 14, 1959) is an American retired professional basketball player and former president of basketball operations of the Los Angeles Lakers of the National Basketball Association (NBA). He played point guard for the Lakers for 13 seasons. After winning championships in high school and college, Johnson was selected first overall in the 1979 NBA draft by the Lakers. He won a championship and an NBA Finals Most Valuable Player Award in his rookie season, and won four more championships with the Lakers during the 1980s. Johnson retired abruptly in 1991 after announcing that he had contracted HIV, but returned to play in the 1992 All-Star Game, winning the All-Star MVP Award. After protests from his fellow players, he retired again for four years, but returned in 1996, at age 36, to play 32 games for the Lakers before retiring for the third and final time.
Johnson's career achievements include three NBA MVP Awards, nine NBA Finals appearances, twelve All-Star games, and ten All-NBA First and Second Team nominations. He led the league in regular-season assists four times, and is the NBA's all-time leader in average assists per game, at 11.2. Johnson was a member of the 1992 United States men's Olympic basketball team ("The Dream Team"), which won the Olympic gold medal in 1992. After leaving the NBA in 1992, Johnson formed the Magic Johnson All-Stars, a barnstorming team that travelled around the world playing exhibition games. Johnson was honored as one of the 50 Greatest Players in NBA History in 1996.
Johnson became a two-time inductee into the Basketball Hall of Fame—being enshrined in 2002 for his individual career, and again in 2010 as a member of the "Dream Team". He was rated the greatest NBA point guard of all time by ESPN in 2007. His friendship and rivalry with Boston Celtics star Larry Bird, whom he faced in the 1979 NCAA finals and three NBA championship series, are well documented.
Since his retirement, Johnson has been an advocate for HIV/AIDS prevention and safe sex, as well as an entrepreneur, philanthropist, broadcaster and motivational speaker. His public announcement of his HIV-positive status in 1991 helped dispel the stereotype, still widely held at the time, that HIV was a "gay disease" that heterosexuals need not worry about; his bravery in making this announcement was widely commended. Named by Ebony magazine as one of America's most influential black businessmen in 2009, Johnson has numerous business interests, and was a part-owner of the Lakers for several years. Johnson also is part of a group of investors that purchased the Los Angeles Dodgers in 2012 and the Los Angeles Sparks in 2014.Management of HIV/AIDS
The management of HIV/AIDS normally includes the use of multiple antiretroviral drugs in an attempt to control HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life-cycle. The use of multiple drugs that act on different viral targets is known as highly active antiretroviral therapy (HAART). HAART decreases the patient's total burden of HIV, maintains function of the immune system, and prevents opportunistic infections that often lead to death.Treatment has been so successful that in many parts of the world, HIV has become a chronic condition in which progression to AIDS is increasingly rare. Anthony Fauci, head of the United States National Institute of Allergy and Infectious Diseases, has written, "With collective and resolute action now and a steadfast commitment for years to come, an AIDS-free generation is indeed within reach." In the same paper, he noted that an estimated 700,000 lives were saved in 2010 alone by antiretroviral therapy. As another commentary in The Lancet noted, "Rather than dealing with acute and potentially life-threatening complications, clinicians are now confronted with managing a chronic disease that in the absence of a cure will persist for many decades."The United States Department of Health and Human Services and the World Health Organization recommend offering antiretroviral treatment to all patients with HIV. Because of the complexity of selecting and following a regimen, the potential for side effects, and the importance of taking medications regularly to prevent viral resistance, such organizations emphasize the importance of involving patients in therapy choices and recommend analyzing the risks and the potential benefits.Men who have sex with men
Men who have sex with men (MSM), also known as males who have sex with males, are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many such men do not sexually identify as gay, homosexual or bisexual.The term MSM was created in the 1990s by epidemiologists to study the spread of disease among men who have sex with men, regardless of identity. The term MSM is often used in medical literature and social research to describe such men as a group for research studies without considering issues of self-identification. It does not describe any specific sexual activity, and which activities are covered by the term depends on context.Reverse transcriptase
A reverse transcriptase (RT) is an enzyme used to generate complementary DNA (cDNA) from an RNA template, a process termed reverse transcription. Reverse transcriptases are used by retroviruses to replicate their genomes, by retrotransposon mobile genetic elements to proliferate within the host genome, by eukaryotic cells to extend the telomeres at the ends of their linear chromosomes, and by some non-retroviruses such as the hepatitis B virus, a member of the Hepadnaviridae, which are dsDNA-RT viruses.
Retroviral RT has three sequential biochemical activities: RNA-dependent DNA polymerase activity, ribonuclease H, and DNA-dependent DNA polymerase activity. Collectively, these activities enable the enzyme to convert single-stranded RNA into double-stranded cDNA. In retroviruses and retrotransposons, this cDNA can then integrate into the host genome, from which new RNA copies can be made via host-cell transcription. The same sequence of reactions is widely used in the laboratory to convert RNA to DNA for use in molecular cloning, RNA sequencing, polymerase chain reaction (PCR), or genome analysis.Ryan White
Ryan Wayne White (December 6, 1971 – April 8, 1990) was an American teenager from Kokomo, Indiana, who became a national poster child for HIV/AIDS in the United States after failing to be re-admitted to school following a diagnosis of AIDS. As a hemophiliac, he became infected with HIV from a contaminated factor VIII blood treatment and, when diagnosed in December 1984, was given six months to live. Doctors said he posed no risk to other students, as AIDS is not an airborne disease and spreads solely through body fluids, but AIDS was poorly understood by the general public at the time. When White tried to return to school, many parents and teachers in Howard County rallied against his attendance due to concerns of the disease spreading through bodily fluid transfer. A lengthy administrative appeal process ensued, and news of the conflict turned Ryan into a popular celebrity and advocate for AIDS research and public education. Surprising his doctors, Ryan White lived five years longer than predicted. He died on April 8, 1990, one month before his high school graduation.
Before Ryan White, AIDS was a disease stigmatized as an illness impacting the gay community, because it was first diagnosed among gay men. That perception shifted as Ryan and other prominent straight HIV-infected people such as Magic Johnson, Arthur Ashe and the Ray brothers appeared in the media to advocate for more AIDS research and public education to address the epidemic. The U.S. Congress passed a major piece of AIDS legislation, the Ryan White CARE Act, shortly after White's death. The Act has been reauthorized twice; Ryan White Programs are the largest provider of services for people living with HIV/AIDS in the United States.Safe sex
Safe sex is sexual activity using methods or devices (such as condoms) to reduce the risk of transmitting or acquiring sexually transmitted infections (STIs), especially HIV. "Safe sex" is also sometimes referred to as safer sex or protected sex to indicate that some safe sex practices do not completely eliminate STI risks. It is also sometimes used to describe methods aimed at preventing pregnancy.
The concept of safe sex emerged in the 1980s as a response to the global AIDS epidemic. Promoting safe sex is now one of the aims of sex education and STI prevention, especially reducing new HIV infections. Safe sex is regarded as a harm reduction strategy aimed at reducing risks of STI transmission.Although some safe sex practices (like condoms) can also be used as birth control (contraception), most forms of contraception do not protect against STIs. Likewise, some safe sex practices, like partner selection and low-risk sex behavior, might not be effective forms of contraception.Sexually transmitted infection
Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs), are infections that are commonly spread by sexual activity, especially vaginal intercourse, anal sex and oral sex. Many times STIs initially do not cause symptoms. This results in a greater risk of passing the disease on to others. Symptoms and signs of disease may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. STIs can be transmitted to an infant before or during childbirth and may result in poor outcomes for the baby. Some STIs may cause problems with the ability to get pregnant.More than 30 different bacteria, viruses, and parasites can be transmitted through sexual activity. Bacterial STIs include chlamydia, gonorrhea, and syphilis. Viral STIs include genital herpes, HIV/AIDS, and genital warts. Parasitic STIs include trichomoniasis. While usually spread by sex, some STIs can be spread by non-sexual contact with donor tissue, blood, breastfeeding, or during childbirth. STI diagnostic tests are usually easily available in the developed world, but this is often not the case in the developing world.The most effective way of preventing STIs is by not having sex. Some vaccinations may also decrease the risk of certain infections including hepatitis B and some types of HPV. Safer sex practices such as use of condoms, having a smaller number of sexual partners, and being in a relationship where each person only has sex with the other also decreases the risk. Circumcision in males may be effective to prevent some infections. During school, comprehensive sex education may also be useful. Most STIs are treatable or curable. Of the most common infections, syphilis, gonorrhea, chlamydia, and trichomoniasis are curable, while herpes, hepatitis B, HIV/AIDS, and HPV are treatable but not curable. Resistance to certain antibiotics is developing among some organisms such as gonorrhea.In 2015, about 1.1 billion people had STIs other than HIV/AIDS. About 500 million were infected with either syphilis, gonorrhea, chlamydia or trichomoniasis. At least an additional 530 million people have genital herpes and 290 million women have human papillomavirus. STIs other than HIV resulted in 108,000 deaths in 2015. In the United States there were 19 million new cases of sexually transmitted infections in 2010. Historical documentation of STIs date back to at least the Ebers papyrus around 1550 BC and the Old Testament. There is often shame and stigma associated with these infections. The term sexually transmitted infection is generally preferred over sexually transmitted disease or venereal disease, as it includes those who do not have symptomatic disease.Subtypes of HIV
One of the obstacles to treatment of the human immunodeficiency virus is its high genetic variability. HIV can be divided into two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the endangered west African primate sooty mangabey. HIV-1 viruses may be further divided into groups. The HIV-1 group M viruses predominate and are responsible for the AIDS pandemic. Group M can be further subdivided into subtypes based on genetic sequence data. Some of the subtypes are known to be more virulent or are resistant to different medications. Likewise, HIV-2 viruses are thought to be less virulent and transmissible than HIV-1 M group viruses, although HIV-2 is known to cause AIDS.
Sexually transmitted infection (STI) (primarily A50–A64, 090–099)