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Human immunodeficiency virus (HIV) is a lentivirus (a member of the retrovirus family) that causes acquired immunodeficiency syndrome (AIDS), a condition in humans in which the immune system begins to fail, leading to life-threatening opportunistic infections. Infection with HIV occurs by the transfer of blood, semen, vaginal fluid, pre-ejaculate, or breast milk. Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. The four major routes of transmission are unsafe sex, contaminated needles, breast milk, and transmission from an infected mother to her baby at birth (perinatal transmission). Screening of blood products for HIV has largely eliminated transmission through blood transfusions or infected blood products in the developed world.
HIV infection in humans is considered pandemic by the World Health Organization (WHO). Nevertheless, complacency about HIV may play a key role in HIV risk. From its discovery in 1981 to 2006, AIDS killed more than 25 million people. In 2005 alone, AIDS claimed an estimated 2.4–3.3 million lives, of which more than 570,000 were children. A third of these deaths are occurring in Sub-Saharan Africa, retarding economic growth and increasing poverty. According to current estimates, HIV is set to infect 90 million people in Africa, resulting in a minimum estimate of 18 million orphans. Antiretroviral treatment reduces both the mortality and the morbidity of HIV infection, but routine access to antiretroviral medication is not available in all countries.
HIV infects primarily vital cells in the human immune system such as helper T cells (to be specific, CD4+ T cells), macrophages, and dendritic cells. HIV infection leads to low levels of CD4+ T cells through three main mechanisms: First, direct viral killing of infected cells; second, increased rates of apoptosis in infected cells; and third, 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.
Most untreated people infected with HIV-1 eventually develop AIDS. These individuals mostly die from opportunistic infections or malignancies associated with the progressive failure of the immune system. HIV progresses to AIDS at a variable rate affected by viral, host, and environmental factors; most will progress to AIDS within 10 years of HIV infection: some will have progressed much sooner, and some will take much longer. Treatment with anti-retrovirals increases the life expectancy of people infected with HIV. Even after HIV has progressed to diagnosable AIDS, the average survival time with antiretroviral therapy was estimated to be more than 5 years as of 2005. Without antiretroviral therapy, someone who has AIDS typically dies within a year.
There are two species of HIV known to exist: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both LAV and HTLV-III. It is more virulent, more infective, 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. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.
HIV infection has four basic stages: incubation period, acute infection, latency stage and AIDS. The initial incubation period upon infection is asymptomatic and usually lasts between two and four weeks. The second stage, acute infection, lasts an average of 28 days and can include symptoms such as fever, lymphadenopathy (swollen lymph nodes), pharyngitis (sore throat), rash, myalgia (muscle pain), malaise, and mouth and esophageal sores.
The latency stage, which occurs third, shows few or no symptoms and can last anywhere from two weeks to twenty years and beyond. AIDS, the fourth and final stage of HIV infection shows as symptoms of various opportunistic infections.
A study of French hospital patients found that approximately 0.5% of HIV-1 infected individuals retain high levels of CD4 T-cells and a low or clinically undetectable viral load without anti-retroviral treatment. These individuals are classified as HIV controllers or long-term nonprogressors.
The initial infection with HIV generally occurs after transfer of body fluids from an infected person to an uninfected one. The first stage of infection, the primary, or acute infection, is a period of rapid viral replication that immediately follows the individual's exposure to HIV leading to an abundance of virus in the peripheral blood with levels of HIV commonly approaching several million viruses per mL.
This response is accompanied by a marked drop in the numbers of circulating CD4+ T cells. This acute viremia is associated in virtually all patients with the activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with antibody production, or seroconversion. The CD8+ T cell response is thought to be important in controlling virus levels, which peak and then decline, as the CD4+ T cell counts rebound. A good CD8+ T cell response has been linked to slower disease progression and a better prognosis, though it does not eliminate the virus.
During this period (usually 2–4 weeks post-exposure) most individuals (80 to 90%) develop an influenza or mononucleosis-like illness called acute HIV infection, the most common symptoms of which may include fever, lymphadenopathy, pharyngitis, rash, myalgia, malaise, mouth and esophageal sores, and may also include, but less commonly, headache, nausea and vomiting, enlarged liver/spleen, weight loss, thrush, and neurological symptoms. Infected individuals may experience all, some, or none of these symptoms. The duration of symptoms varies, averaging 28 days and usually lasting at least a week.
Because of the nonspecific nature of these symptoms, they are often not recognized as signs of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. As a consequence, these primary symptoms are not used to diagnose HIV infection, as they do not develop in all cases and because many are caused by other more common diseases. However, recognizing the syndrome can be important because the patient is much more infectious during this period.
During this stage of infection early initiation of antiretroviral therapy significantly improves survival, as compared with deferred therapy. |- style="background:#efefef;" ! abbr="Route" | Exposure Route ! abbr="Infections" | Estimated infectionsper 10,000 exposuresto an infected source |- | style="text-align:left"| Blood transfusion | 9,000 |- | style="text-align:left"| Childbirth | 2,500 |- | style="text-align:left"| Needle-sharing injection drug use | 67 |- | style="text-align:left"| Percutaneous needle stick | 30 |- | style="text-align:left"| Receptive anal intercourse (2009 and 2010 studies) | 170‡ [30–890] |- | style="text-align:left"| Insertive anal intercourse for uncircumcised men (2010 study) | 62a [7-168] |- | style="text-align:left"| Insertive penile-vaginal intercourse | 5 |- | colspan=5 style="border-right:0;"| Bracketed values represent 95% confidence interval † "best-guess estimate" ‡ Pooled transmission probability estimate |- | colspan=5 style="border-right:0;"| a Other studies found insufficient evidence that male circumcision protects against HIV infection among men who have sex with men |- | colspan=5 style="border-right:0;"| b Oral trauma, sores, inflammation, concomitant sexually transmitted infections, ejaculation in the mouth, and systemic immune suppression may increase HIV transmission rate. |}
Three main transmission routes for HIV have been identified. HIV-2 is transmitted much less frequently by the mother-to-child and sexual route than HIV-1.
Randomized, controlled trials in which uncircumcised men were randomly assigned to be medically circumcised in sterile conditions and given counseling and other men were not circumcised, have been conducted in South Africa, Kenya, and Uganda showing reductions in female-to-male sexual HIV transmission of 60%, 53%, and 51% respectively. As a result, a panel of experts convened by WHO and the UNAIDS Secretariat has "recommended that male circumcision now be recognized as an additional important intervention to reduce the risk of heterosexually acquired HIV infection in men." Among men who have sex with men, there is insufficient evidence that male circumcision protects against HIV infection or other Sexually Transmitted Infections.
Studies of HIV among women who have undergone female genital cutting (FGC) have reported mixed results, but with some evidence of increased risk of transmission. Programmes that aim to encourage sexual abstinence while also encouraging and teaching safer sex strategies for those who are sexually active can reduce short- and long-term HIV risk behaviour among young people in high-income countries, according to a 2007 Cochrane Review of studies.
HIV has been found at low concentrations in the saliva, tears and urine of infected individuals, but there are no recorded cases of infection by these secretions and the potential risk of transmission is negligible. It is not possible for mosquitoes to transmit HIV.
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, yet large for a virus. It is composed of two copies of positive 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 glycoprotein complex enables the virus to attach to and fuse with target cells to initiate the infectious cycle.
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. 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 cell protein that deaminates DNA:RNA hybrids and/or interferes with the Pol protein). 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. This CCR5 coreceptor 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 tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus.
T-tropic isolates, or syncitia-inducing (SI) strains 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 these cells. HIV that use only the CCR5 receptor are termed R5; those that only use CXCR4 are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection 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 with R5 virus as the mutation stops HIV from binding to this coreceptor, 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 is passed 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. How this selective process works is still under investigation, but one model is that spermatozoa may selectively carry R5 HIV as they possess both CCR3 and CCR5 but not CXCR4 on their surface and that genital epithelial cells preferentially sequester X4 virus. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants appear 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% of AIDS patients can harbour viruses of the SI, and presumably the X4, phenotype.
HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution. The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of coreceptor 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 more successful at transmission will be selected.
Entry to the cell begins through interaction of the trimeric envelope complex (gp160 spike) and both CD4 and a chemokine receptor (generally either CCR5 or CXCR4, but others are known to interact) on the cell surface. The gp160 spike contains binding domains for both CD4 and chemokine receptors. 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.
During viral replication, the integrated DNA provirus is transcribed into mRNA, which is then spliced into smaller pieces. These small pieces 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 accumulates in the nucleus, it binds to viral mRNAs and allows unspliced RNAs to leave the nucleus, where they are otherwise retained until spliced. At this stage, the structural proteins Gag and Env are produced from the full-length mRNA. The full-length RNA is actually the virus genome; it binds to the Gag protein and is packaged into new virus particles.
HIV-1 and HIV-2 appear to package their RNA differently; HIV-1 will bind to any appropriate RNA, whereas HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself. This may mean that HIV-1 is better able to mutate (HIV-1 infection progresses to AIDS faster than HIV-2 infection and is responsible for the majority of global infections).
This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day. 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" 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. Both SIVcpz and HIV-1 appear to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to the virus. 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. Coinfection 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. For example, less than 1% of the sexually active urban population in Africa have been tested and this proportion is even lower in rural populations.
HIV-1 testing consists of initial screening with an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a nonreactive 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., Western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA 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. Generally, 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.
There is currently no publicly available vaccine or cure for HIV or AIDS. However, a vaccine that is a combination of two previously unsuccessful vaccine candidates was reported in September 2009 to have resulted in a 30% reduction in infections in a trial conducted in Thailand. Additionally, a course of antiretroviral treatment administered immediately after exposure, referred to as post-exposure prophylaxis, is believed to reduce the risk of infection if begun as quickly as possible. In July 2010, a vaginal gel containing tenofovir, a reverse transcriptase inhibitor, was shown to reduce HIV infection rates by 39 percent in a trial conducted in South Africa.
However, due to the incomplete protection provided by the vaccine and/or post-exposure prophylaxis, the avoidance of exposure to the virus is expected to remain the only reliable way to escape infection for some time yet. Current treatment for HIV infection consists of highly active antiretroviral therapy, or HAART. This has been highly beneficial to many HIV-infected individuals since its introduction in 1996, when the protease inhibitor-based HAART initially became available. Current HAART options are combinations (or "cocktails") consisting of at least three drugs belonging to at least two types, or "classes," of antiretroviral agents. Typically, these classes are two nucleoside analogue reverse transcriptase inhibitors (NARTIs or NRTIs) plus either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor (NNRTI).
There is no empirical evidence for withholding treatment at any stage of HIV infection,
New classes of drugs such as entry inhibitors provide treatment options for patients who are infected with viruses already resistant to common therapies, although they are not widely available and not typically accessible in resource-limited settings. Because AIDS progression in children is more rapid and less predictable than in adults, particularly in young infants, more aggressive treatment is recommended for children than adults. In developed countries where HAART is available, doctors assess their patients thoroughly: measuring the viral load, how fast CD4 declines, and patient readiness. They then decide when to recommend starting treatment.
HAART neither cures the patient nor does it uniformly remove all symptoms; high levels of HIV-1, often HAART resistant, return if treatment is stopped. Moreover, it would take more than a lifetime for HIV infection to be cleared using HAART. Despite this, many HIV-infected individuals have experienced remarkable improvements in their general health and quality of life, which has led to a large reduction in HIV-associated morbidity and mortality in the developed world. One study suggests the average life expectancy of an HIV infected individual is 32 years from the time of infection if treatment is started when the CD4 count is 350/µL. Life expectancy is further enhanced if antiretroviral therapy is initiated before the CD4 count falls below 500/µL.
The reasons for non-adherence and non-persistence with HAART are varied and overlapping. Major psychosocial issues, such as poor access to medical care, inadequate social supports, psychiatric disease and drug abuse contribute to non-adherence. The complexity of these HAART regimens, whether due to pill number, dosing frequency, meal restrictions or other issues along with side effects that create intentional non-adherence also contribute to this problem. The side effects include lipodystrophy, dyslipidemia, insulin resistance, an increase in cardiovascular risks, and birth defects.
Anti-retroviral drugs are expensive, and the majority of the world's infected individuals do not have access to medications and treatments for HIV and AIDS. Research to improve current treatments includes decreasing side effects of current drugs, further simplifying drug regimens to improve adherence, and determining the best sequence of regimens to manage drug resistance. Unfortunately, only a vaccine is thought to be able to halt the pandemic. This is because a vaccine would cost less, thus being affordable for developing countries, and would not require daily treatment.
The failure of vaccine candidates to protect against HIV infection and progression to AIDS has led to a renewed focus on the biological mechanisms responsible for HIV latency. A limited period of therapy combining anti-retrovirals with drugs targeting the latent reservoir may one day allow for total eradication of HIV infection.
A combination of peptides that stimulate integration together with the protease inhibitor Ro 31-8959 cause apoptotic cell death of cultured cells that were infected with HIV without apparent damage to uninfected cells. No animal or human tests of this combination have been reported.
As new treatments continue to be developed and because HIV continues to evolve resistance to treatments, estimates of survival time are likely to continue to change. Without antiretroviral therapy, death normally occurs within a year after the individual progresses to AIDS. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility and immune function health care and co-infections,
UNAIDS and the WHO estimate that AIDS has killed more than 25 million people since it was first recognized in 1981, making it one of the most destructive pandemics in recorded history. Despite recent improved access to antiretroviral treatment and care in many regions of the world, the AIDS pandemic claimed an estimated 2.8 million (between 2.4 and 3.3 million) lives in 2005 of which more than half a million (570,000) were children.
Sub-Saharan Africa remains by far the worst-affected region, with an estimated 22.5 million people currently living with HIV (67% of the global total), 1.3 million deaths (72% of the global total) and 1.8 million new infections (69% of the global total). However, the number of new infections declined by 19% across the region between 2001 and 2009, and by more than 25% in 22 sub-Saharan African countries during this period. Asia are the second-worst affected with 4.9 million people living with HIV (15% of the global total). This is the first comprehensive evaluation of the World Bank's HIV/AIDS support to countries, from the beginning of the epidemic through mid-2004. Because the Bank aims to assist in implementation of national government programmes, their experience provides important insights on how national AIDS programmes can be made more effective.
The development of HAART as effective therapy for HIV infection has substantially reduced the death rate from this disease in those areas where these drugs are widely available. As the life expectancy of persons with HIV has increased in countries where HAART is widely used, the continuing spread of the disease has caused the number of persons living with HIV to increase substantially.
In Africa, the number of mother-to-child-transmission (MTCT) cases and the prevalence of AIDS is beginning to reverse decades of steady progress in child survival. Countries such as Uganda are attempting to curb the MTCT epidemic by offering VCT (voluntary counselling and testing), PMTCT (prevention of mother-to-child transmission) and ANC (ante-natal care) services, which include the distribution of antiretroviral therapy.
Both HIV-1 and HIV-2 are believed to have originated in West-Central Africa and to have jumped species (a process known as zoonosis) from non-human primates to humans. HIV-1 appears to have originated in southern Cameroon through the evolution of SIV(cpz), 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 SIV(smm), a virus of the sooty mangabey (Cercocebus atys atys), an Old World monkey living in litoral West Africa (from southern Senegal to western Ivory Coast. 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.
There is evidence that humans who participate in bushmeat activities, either as hunters or as bushmeat vendors, commonly acquire SIV. However, only a few of these infections were able to cause epidemics in humans, and all did so in the late 19th—early 20th century. To explain why HIV became epidemic only by that time, there are several theories, each invoking specific driving factors that may have promoted SIV adaptation to humans, or initial spread: social changes following colonialism, rapid transmission of SIV through unsafe or unsterile injections (that is, injections in which the needle is reused without being sterilised), colonial abuses and unsafe smallpox vaccinations or injections, or prostitution and the concomitant high frequency of genital ulcer diseases (such as syphilis) in nascent colonial cities
In 1983, two separate research groups led by Robert Gallo 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 an AIDS patient 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 lymphadenopathy (swelling of the lymph nodes) of the neck and physical weakness, two classic symptoms of AIDS. 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). Harald zur Hausen also shared the Prize for his discovery that human papilloma virus leads to cervical cancer, but Gallo was left out. Montagnier said he was "surprised" Gallo was not recognized by the Nobel Committee: "It was important to prove that HIV was the cause of AIDS, and Gallo had a very important role in that. I'm very sorry for Robert Gallo."
A small group of individuals continue to dispute the connection between HIV and AIDS, the existence of HIV itself, or the validity of HIV testing and treatment methods. These claims, known as AIDS denialism, have been examined and rejected by the scientific community. However, they have had a significant political impact, particularly in South Africa, where the government's official embrace of AIDS denialism was responsible for its ineffective response to that country's AIDS epidemic, and has been blamed for hundreds of thousands of avoidable deaths and HIV infections.
Category:HIV/AIDS Category:Lentiviruses Category:Sexually transmitted diseases and infections Category:Immunodeficiency Category:Discovery and invention controversies Category:Initialisms Category:Causes of death
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Name | Stephen Fry |
---|---|
Caption | Fry in Happy Birthday to GNU (2008) |
Birth name | Stephen John Fry |
Birth date | August 24, 1957 |
Birth place | Hampstead, London, England |
Occupation | Actor, comedian, author, journalist, broadcaster, film director |
Years active | 1982–present |
Partner | Daniel Cohen (1995–2010)Steven Webb (2010-present) |
Religion | None (atheist) |
Website | http://www.stephenfry.com |
Signature | Stephen Fry's signature.jpg |
Signature size | 100px |
Stephen John Fry (born 24 August 1957) is an English actor, screenwriter, author, playwright, journalist, poet, comedian, television presenter and film director, and a director of Norwich City Football Club. He first came to attention in the 1981 Cambridge Footlights Revue presentation "The Cellar Tapes", which also included Hugh Laurie, Emma Thompson and Tony Slattery. With Hugh Laurie, as the comedy double act Fry and Laurie, he co-wrote and co-starred in A Bit of Fry & Laurie, and the duo also played the title roles in Jeeves and Wooster.
As a solo actor, Fry played the lead in the film Wilde, was Melchett in the BBC television series Blackadder, starred as the title character Peter Kingdom in the ITV series Kingdom, and is the host of the quiz show QI. He also presented a 2008 television series Stephen Fry in America, which saw him travelling across all 50 U.S. states in six episodes. Fry has a recurring guest role as Dr. Gordon Wyatt on the Fox crime series Bones.
Apart from his work in television, Fry has contributed columns and articles for newspapers and magazines, and has written four novels and two volumes of autobiography, Moab Is My Washpot and . He also appears frequently on BBC Radio 4, starring in the comedy series Absolute Power, being a frequent guest on panel games such as Just a Minute, and acting as chairman for I'm Sorry I Haven't a Clue, where he was one of a trio of hosts who succeeded the late Humphrey Lyttelton. He is also known to British audiences everywhere as the reader of all seven Harry Potter novels in their audiobook versions.
At 17, after leaving Norfolk College of Arts and Technology, Fry absconded with a credit card stolen from a family friend, was arrested in Swindon, and as a result spent three months in Pucklechurch Prison on remand.
Following his release he resumed education at City College Norwich, promising administrators that he would study rigorously to sit the Cambridge entrance exams. He passed well enough to gain a scholarship to Queens' College, Cambridge. At Cambridge, Fry joined the Cambridge Footlights, appeared on University Challenge, and gained a degree in English literature. It was at the Footlights that Fry met his future comedy collaborator Hugh Laurie.
Forgiving Fry and Laurie for The Crystal Cube, the BBC commissioned a sketch show in 1986 that was to become A Bit of Fry & Laurie. The programme ran for 26 episodes spanning four series between 1986 and 1995, and was very successful. During this time Fry starred in Blackadder II as Lord Melchett, made a guest appearance in as the Duke of Wellington, then returned to a starring role in Blackadder Goes Forth as General Melchett. In 1988, he became a regular contestant on the popular improvisational comedy radio show Whose Line Is It Anyway?. However, when it moved to television, he only appeared three times: twice in the first series and once in the ninth.
Between 1990 and 1993, Fry starred as Jeeves (alongside Hugh Laurie's Bertie Wooster) in Jeeves and Wooster, 23 hour-long adaptations of P.G. Wodehouse's novels and short stories.
In 1998 BBC Two aired a Malcolm Bradbury adaptation of the Mark Tavener 1989 novel, In the Red with Fry taking the part of the Controller of BBC Radio 2.
In 2000, Fry played the role of Professor Bellgrove in the BBC serial Gormenghast which was an adaptation of the first two novels of Mervyn Peake's Gormenghast series.
In 2010 he filmed a cameo role in Ros na Rún, an Irish language soap opera broadcast in Ireland, Scotland and the United States. Fry learned Irish for the role. He also came together with Laurie for a retrospective of their partnership titled Fry and Laurie Reunited.
In 2010 Fry took part in a Christmas series of Short Films called 'Little Crackers'. Fry's short is based on a story from his childhood at school.
Fry has also been involved in nature documentaries, having narrated Spectacled Bears: Shadow of the Forest for the BBC Natural World series in 2008. In the television series Last Chance to See, Fry together with zoologist Mark Carwardine sought out endangered species, some of which were featured in Douglas Adams and Carwardine's 1990 book/radio series of the of the same name. The resulting programmes were broadcast in 2009.
From 2007 to 2009, Fry appeared in and was executive producer for the legal drama Kingdom, which ran for three series on ITV1. He has also taken up a recurring guest role as psychiatrist Dr. Gordon Wyatt in the popular American drama Bones.
On 7 May 2008, Fry gave a speech as part of a series of BBC lectures on the future of public service broadcasting in the United Kingdom, which he later recorded for a podcast.
Fry also narrates the English language version of the Spanish children's animated series Pocoyo.
In 2003, Fry made his directorial debut with Bright Young Things, adapted by himself from Evelyn Waugh's Vile Bodies. In 2001, he began hosting the BAFTA Film Awards, a role from which he stepped down in 2006. Later that same year, he wrote the English libretto and dialogue for Kenneth Branagh's film adaptation of The Magic Flute.
Fry continues to make regular film appearances, notably in treatments of literary cult classics. He served as narrator in the 2005 film version of The Hitchhiker's Guide to the Galaxy, and in 2005 he appeared in both A Cock and Bull Story, based on Tristram Shandy, and as a non-conforming TV Presenter who challenges the fascist state in V for Vendetta. In 2006, he played the role of gadget-master Smithers in Stormbreaker, and in 2007 he appeared as himself hosting a quiz in St Trinian's. In 2007, Fry wrote a script for a remake of The Dam Busters for director Peter Jackson.
(2008)"]] In 2008, he participated in a film celebrating the 25th anniversary of GNU, Happy Birthday to GNU. Fry was offered a role in Valkyrie but was unable to participate. Fry starred in the Tim Burton version of Alice in Wonderland, as the voice of The Cheshire Cat, alongside Johnny Depp, Helena Bonham Carter and Anne Hathaway. He will play Mycroft Holmes in the sequel to Sherlock Holmes directed by Guy Ritchie.
In 2007, he hosted Current Puns, an exploration of wordplay, and Radio 4: This Is Your Life, to celebrate the radio station's 40th anniversary. He also interviewed Tony Blair as part of a series of podcasts released by 10 Downing Street.
In February 2008, Fry began presenting podcasts entitled Stephen Fry's Podgrams, in which he recounts his life and recent experiences.
In August 2008 he hosted Fry's English Delight, a three-part series on BBC Radio 4 about metaphor, quotation and cliché. Fry returned with a second series a year later.
In the summer 2009 series of I'm Sorry I Haven't a Clue, Fry was one of a trio of hosts replacing Humphrey Lyttelton (the others being Jack Dee and Rob Brydon).
He also lends his voice to the introduction and stings for Phill Jupitus' fortnightly podcast, The Perfect Ten.
Following three one-man shows in Australia, Fry announced a "sort of stand-up" performance at The Royal Albert Hall in London for September 2010. Depending on its reception, Fry may tour nationally.
When writing a book review for Tatler, Fry wrote under an alias, Williver Hendry, editor of A Most Peculiar Friendship: The Correspondence of Lord Alfred Douglas and Jack Dempsey, a field close to Fry's heart as an Oscar Wilde enthusiast. Once a columnist in The Listener and The Daily Telegraph, he now writes a weekly technology column in the Saturday edition of The Guardian. His blog attracted more than 300,000 visitors in its first two weeks of existence. After its release, it reached No. 1 on the UK Album Chart list.
On 2 January 2010 it was announced that Fry was "switching off his connections with the outside world" in order to complete a second volume of his autobiography.
Fry's use of the word "luvvie" in The Guardian on 2 April 1988 is given by the Oxford English Dictionary as the earliest recorded use of the word.
In October 2009 Fry sparked debate amongst users again when he announced an intention to leave the social networking site after criticism from another user on Twitter. He retracted the intention the next day. In October 2010, Fry left Twitter for a few days following press criticism of a quote taken from an interview he had given, with a farewell message of "Bye bye". After returning, Fry explained that he had left Twitter to "avoid being sympathised with or told about an article I would otherwise never have got wind of".
In November 2009 Fry's Twitter account reached 1,000,000 followers. He commemorated the million followers milestone with a humorous video blog in which a 'Step Hen Fry' clone speaks from the year 2034 where MySpace, Facebook and Twitter have combined to form 'Twit on MyFace'.
In November 2010 Fry achieved 2,000,000 followers on Twitter. He welcomed his 2 millionth follower, mobijack, with a blog entry describing Fry's view of the pros and cons of this form of communication.
In December 2006 he was ranked sixth for the BBC's Top Living Icon Award, was featured on The Culture Show, and was voted most intelligent man on television by readers of Radio Times. The Independent on Sunday Pink List named Fry the second most influential gay person in Britain in May 2007. He had taken the twenty-third position on the list the previous year. Later the same month he was announced as the 2007 BT Mind Champion of the Year in recognition of the awareness raised about bipolar disorder by his documentary The Secret Life of a Manic Depressive. Fry was also nominated in "Best Entertainment Performance" for QI and "Best Factual Series" for Secret Life of the Manic Depressive at the 2007 British Academy Television Awards. That same year, Broadcast magazine listed Fry at number four in its "Hot 100" list of influential on-screen performers, describing him as a polymath and a "national treasure". He was also granted a lifetime achievement award at the British Comedy Awards on 5 December 2007 and the Special Recognition Award at the National Television Awards on 20 January 2010.
BBC Four dedicated two nights of programming to Fry on 17 and 18 August 2007, in celebration of his 50th birthday. The first night, comprising programs featuring Fry, began with a sixty-minute documentary entitled . The second night was composed of programs selected by Fry, as well as a 60-minute interview with Mark Lawson and a half-hour special, Stephen Fry: Guilty Pleasures. Stephen Fry Weekend proved such a ratings hit for BBC Four that it was repeated on BBC Two on 16 and 17 of that September.
On 15 September 2010, Fry, along with 54 other public figures, signed an open letter published in The Guardian, stating their opposition to Pope Benedict XVI's visit to the United Kingdom being a state visit.
Fry was an active supporter of the Labour Party for many years, and appeared in a party political broadcast on its behalf with Hugh Laurie and Michelle Collins in November 1993. Despite this, he did not vote in the 2005 General Election because of the stance of both the Labour and Conservative parties with regard to the Iraq War. Despite his praising of the Blair/Brown government for social reform, Fry has been critical of the Labour Party's "Third Way" concept. He is on cordial terms with Prince Charles (despite a mild parody Fry performed in his role of King Charles I in the comedy programme ), through his work with the Prince's Trust. He attended the wedding of the Prince of Wales to Camilla Parker-Bowles in 2005.
Fry is a friend of British comedian and actor (and Blackadder co-star) Rowan Atkinson and was best man at Atkinson's wedding to Sunetra Sastry at the Russian Tea Room in New York City. He was also a friend of British actor John Mills.
His best friend is Hugh Laurie, whom he met while both were at Cambridge and with whom he has collaborated many times over the years. He was best man at Laurie's wedding and is godfather to all three of his children.
A fan of cricket, Fry has claimed to be related to former England cricketer C.B. Fry, and was recently interviewed for the Ashes Fever DVD, reporting on England's victory over Australia in the 2005 Ashes series. Regarding football, he is a supporter of Norwich City (as mentioned in Ashes Fever), and is a regular visitor to Carrow Road. Fry has a sister named Jo Crocker who was assistant director on Bright Young Things.
Fry has talked on occasion about his passion for whisky. He visited the Woodford Reserve whiskey distillery in Kentucky, US in his BBC series Stephen Fry in America. Stephen cites his favourite whisky as the Master of Malt 19 year old Tomatin.
He has been described as "deeply dippy for all things digital", claims to have bought the third Macintosh computer sold in the UK (his friend Douglas Adams bought the first two) and jokes that he has never encountered a smartphone that he has not bought. He counts Wikipedia among his favourite websites "because I like to find out that I died, and that I'm currently in a ballet in China, and all the other very accurate and important things that Wikipedia brings us all."
Fry has a long interest in Internet production, including his own website since 1997. His current site, The New Adventures of Mr Stephen Fry, has existed since 2002 and has attracted many visitors following his first blog in September 2007, which comprised a 6,500 word "blessay" on smartphones. In February 2008, Fry launched his private podcast series, Stephen Fry's Podgrams, and a forum, including discussions on depression and activities in which Fry is involved. The website content is created by Stephen Fry and produced by Andrew Sampson. Fry is also a supporter of GNU and the Free Software Foundation. For the 25th anniversary of the GNU operating system, Fry appeared in a video explaining some of the philosophy behind GNU by likening it to the sharing found in science. In October 2008, he began posting to his Twitter stream, which he regularly updates. On 16 May 2009, he celebrated the 500,000-follower mark: "Bless my soul 500k followers. And I love you all. Well, all except that silly one. And that's not you."
On 30 April 2008, Fry signed an open letter, published in The Guardian newspaper by some well known Jewish personalities, stating their opposition to celebrating the 60th anniversary of the founding of the State of Israel. Furthermore, he is a signatory member of the British Jews for Justice for Palestinians organisation, which campaigns for Palestinian rights.
A year later, The Guardian published a letter from Fry addressing his younger self, explaining how his future is soon to unfold, reflecting on the positive progression towards gay acceptance and openness around him, and yet not everywhere, while warning on how "the cruel, hypocritical and loveless hand of religion and absolutism has fallen on the world once more".
Fry was among over one hundred signatories to a statement published by Sense About Science on 4 June 2009, condemning British libel laws and their use to "severely curtail the right to free speech on a matter of public interest."
He was recently made a Distinguished Supporter of the British Humanist Association, stating: "it is essential to nail one’s colours to the mast as a humanist.".
On 6 October 2009, Fry was interviewed by Jon Snow on Channel 4 News as a signatory of a letter to British Conservative Party leader David Cameron expressing concern about the party's relationship with Poland's opposition national conservative Law and Justice party in the European Parliament. During the interview, he stated:
There has been a history, let's face it, in Poland of a right-wing catholicism which has been deeply disturbing for those of us who know a little history, and remember which side of the border Auschwitz was on and know the stories, and know much of the anti-semitic, and homophobic and nationalistic elements in countries like Poland.The remark prompted a complaint from the Polish Embassy in London, an editorial in The Economist and criticism from British Jewish historian David Cesarani. Fry has since posted an apology in a six-page post on his personal weblog, in which he stated:
I offer no excuse. I seemed to imply that the Polish people had been responsible for the most infamous of all the death factories of the Third Reich. I didn't even really at the time notice the import of what I had said, so gave myself no opportunity instantly to retract the statement. It was a rubbishy, cheap and offensive remark that I have been regretting ever since.
I take this opportunity to apologise now. I said a stupid, thoughtless and fatuous thing. It detracted from and devalued my argument, such as it was, and it outraged and offended a large group of people for no very good reason. I am sorry in all directions, and all the more sorry because it is no one's fault but my own, which always makes it so much worse. He suffered a nervous breakdown in 1995 while appearing in a West End play called Cell Mates and subsequently walked out of the production, prompting its early closure and incurring the displeasure of co-star Rik Mayall and playwright Simon Gray. Mayall's comedy partner, Adrian Edmondson, made light of the subject in his and Mayall's second Bottom live show. After walking out of the production, Fry went missing for several days while contemplating suicide. He abandoned the idea and left the United Kingdom by ferry, eventually resurfacing in Belgium. Fry has spoken publicly about his experience with bipolar disorder, which was also depicted in the documentary Stephen Fry: The Secret Life of the Manic-Depressive. In the programme, he interviewed other sufferers of the illness including celebrities Carrie Fisher, Richard Dreyfuss and Tony Slattery. Also featured were chef Rick Stein, whose father committed suicide, Robbie Williams, who talks of his experience with major depression, and comedienne/former mental health nurse Jo Brand.In 2009, Fry lent his support to a campaign led by the human rights organisation Reprieve to prevent the execution of Akmal Shaikh, a British national who suffered from bipolar disorder, yet, despite calls for clemency, was executed in the People's Republic of China for drug trafficking.
Fry is six feet five inches (196 cm) tall.
In January 2008, he broke his arm while filming Last Chance to See in Brazil. He later explained in a podcast how the accident happened: while climbing aboard a boat, he slipped between it and the dock, and, while stopping himself from falling into the water, his body weight caused his right humerus to snap. The damage was more severe than first thought: the resulting vulnerability to his radial nerve—he was at risk of losing the use of his arm—was not diagnosed until he saw a consultant in the UK.
As the host of QI, Fry has revealed that he is allergic to both champagne and bumble bee stings.
Appearing on Top Gear in 2009, Fry had lost a significant amount of weight, prompting host Jeremy Clarkson to ask jokingly, "Where's the rest of you?" Fry explained that he had shed a total of , attributing the weight loss to doing a lot of walking while listening to downloaded Audiobooks.
Business
In 2008, Fry formed SamFry Ltd, with long-term collaborator Andrew Sampson, to produce and fund new content, as well as manage his official website.
Bibliography
References
External links
Five Minutes With: Stephen Fry, interview with Matthew Stadlen for the BBC
Category:1957 births Category:Alternate history writers Category:Alumni of Queens' College, Cambridge Category:Audio book narrators Category:British actors of Hungarian descent Category:English Jews Category:English atheists Category:English comedians Category:English comedy writers Category:English film actors Category:English film directors Category:English fraudsters Category:English game show hosts Category:English humanists Category:English novelists Category:English podcasters Category:English radio writers Category:English science fiction writers Category:English television actors Category:English television writers Category:Gay actors Category:Gay writers Category:Jewish actors Category:Jewish atheists Category:Jewish comedians Category:Jewish writers Category:LGBT Jews Category:LGBT comedians Category:LGBT directors Category:LGBT people from England Category:LGBT screenwriters Category:LGBT television personalities Category:LGBT writers from the United Kingdom Category:Living people Category:Old Uppinghamians Category:Outstanding Performance by a Cast in a Motion Picture Screen Actors Guild Award winners Category:People associated with the University of Dundee Category:People from Hampstead Category:People with bipolar disorder Category:QI Category:Real people associated with the Harry Potter books Category:Rectors of the University of Dundee Category:Sidewise Award winning authors Category:University Challenge contestants Category:Atheism activists
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Name | Lara Roxx |
---|---|
Gender | female |
Birth date | December 12, 1982 |
Birth place | Montreal, Quebec, Canada |
Height | |
Measurements | 34B-25-35 |
Eye color | Grey |
Hair color | Black |
Alias | Lara Cox, Lana Roxx |
Imdb | 1597377 |
Iafd | LaraCox |
Afdb | 32287 |
Spelling |
James and Roxx have been banned from any further porn production in the US. At the end of April 2004, it was confirmed that Jessica Dee and Miss Arroyo, after having worked with James, also tested positive for HIV.
Roxx, on learning about James being HIV-positive, said, "It totally made me realize how I trusted this system that wasn't to be trusted at all, because it obviously doesn't work," and "I thought porn people were the cleanest people in the world."
This outbreak, the first in four years, led to a voluntary moratorium on porn production for 30 days (60 days was originally announced), starting in April 2004, while it confirmed all possible contacts among porn performers. No adult video production companies were required to comply.
Roxx appeared on Entertainment Tonight, in an ABC special. In 2007, on an episode of The Maury Povich Show, she came on to talk to wild teens about her past, and to help them prevent making the mistakes she made in the past.
She is currently working on various projects linked to the 2004 events, such as her Lara Roxx Foundation, which is committed to educating the public and preventing the spread of HIV/AIDS.
Category:1982 births Category:Canadian expatriates in the United States Category:Canadian pornographic film actors Category:Female pornographic film actors Category:HIV-positive people Category:Living people Category:People from Montreal Category:Date of birth missing (living people)
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Hans Rosling (born 27 July 1948 in Uppsala, Sweden) is a Swedish medical doctor, academic, statistician and public speaker. He is Professor of International Health at Karolinska Institute and Director of the Gapminder Foundation, which developed the Trendalyzer software system. From 1967 to 1974 he studied statistics and medicine at Uppsala University, and in 1972 he studied public health at St. John's Medical College, Bangalore. He became a licenced physician in 1976 and from 1979 to 1981 he served as District Medical Officer in Nacala in northern Mozambique.
Rosling presented the television documentary The Joy of Stats, which was broadcast in the United Kingdom by BBC Four in December 2010.
Rosling is also a sword swallower, as demonstrated in the final moments of his second talk at the TED conference. In 2009 he was listed as one of 100 leading global thinkers by Foreign Policy Magazine.
Category:1948 births Category:People from Uppsala Category:Karolinska Institutet faculty Category:Swedish bloggers Category:Public health education Category:Living people Category:Sword swallowers
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Beck was considered to be instrumental in capturing the remaining native birds on Guam, such as the Guam rail or kingfisher, whose numbers had been decimated due to the accidental introduction of the brown tree snake. Beck, a former Guamanian Department of Agriculture Division of Aquatic and Wildlife Resources wildlife supervisor, established captive breeding programs on Guam. For example, Beck established a stable breeding population of Guam rails, or ko'ko', in captivity and released them on the neighboring island of Rota, in the Northern Mariana Islands. Wildlife biologist Gary Wiles was quoted in the Pacific Daily News as crediting Beck for saving the species, "Bob was one of the first to begin organizing catching the birds so they could be brought into captivity, held there and bred. He started a captive population. We still have Guam rails today because of his efforts."
Beck was also a driving force for the establishment of captive breeding programs for native Guam rails in zoos throughout the United States. The Guam rail breeding program initially began at just three zoos, the Bronx Zoo, the Philadelphia Zoo and the Smithsonian National Zoological Park in Washington, D.C. . However, the program has been expanded to include seventeen zoos nationwide, including the Audubon Zoo in New Orleans and the San Diego Zoo. There are now over 120 individual Guam rails at the program's facilities on Guam and thirty-five Guam rails on the mainland United States.
Bob Beck stayed on Guam and remained involved in his programs following his retirement in 2003. He died in Tamuning, Guam, on May 24, 2008 at the age of 63. He was married to his wife, Patricia Rossett, from 1978 until 1992. The couple had two children, Erik R. Beck and Joanna R. Beck.
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