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.

Classification

HIV is a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses have many common morphologies and biological properties. 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 of the target cell, the viral RNA genome is converted to double-stranded DNA by a virally encoded reverse transcriptase that is present in the virus particle. This viral DNA is then integrated into the cellular DNA by a virally encoded integrase, along with host cellular co-factors, so that the genome can be transcribed. After the virus has infected the cell, two pathways are possible: either the virus becomes latent and the infected cell continues to function or the virus becomes active and replicates, and a large number of virus particles that can then infect other cells are liberated.

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.

Signs and symptoms

Infection with HIV-1 is associated with a progressive decrease of the CD4⁺ T cell count and an increase in viral load. The stage of infection can be determined by measuring the patient's CD4⁺ T cell count, and the level of HIV in the blood.

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.

Acute infection

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.

Chronic infection

A strong immune defense reduces the number of viral particles in the blood stream, marking the start of secondary or chronic HIV infection. The secondary stage of HIV infection can vary between two weeks and 20 years. During this phase of infection, HIV is active within lymph nodes, which typically become persistently swollen, in response to large amounts of virus that becomes trapped in the follicular dendritic cells (FDC) network. The surrounding tissues that are rich in CD4⁺ T cells may also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who are in this phase are still infectious. During this time, CD4⁺ CD45RO⁺ T cells carry most of the proviral load.

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) | 62^a [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.

Sexual

The majority of HIV infections are acquired through unprotected sexual relations. Complacency about HIV plays a key role in HIV risk. The rate for receptive anal intercourse is much higher, 1.7% per act. However, spermicide may actually increase the transmission rate.

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.

Blood products

In general, if infected blood comes into contact with any open wound, HIV may be transmitted. This transmission route can account for infections in intravenous drug users, hemophiliacs, and recipients of blood transfusions (though most transfusions are checked for HIV in the developed world) and blood products. It is also of concern for persons receiving medical care in regions where there is prevalent substandard hygiene in the use of injection equipment, such as the reuse of needles in Third World countries. Health care workers such as nurses, laboratory workers, and doctors have also been infected, although this occurs more rarely. Since transmission of HIV by blood became known medical personnel are required to protect themselves from contact with blood by the use of universal precautions. People who give and receive tattoos, piercings, and scarification procedures can also be at risk of infection.

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.

Mother-to-child

The transmission of the virus from the mother to the child can occur in utero (during pregnancy), intrapartum (at childbirth), or via breast feeding. In the absence of treatment, the transmission rate up to birth between the mother and child is around 25%. However, where combination antiretroviral drug treatment and Cesarian section are available, this risk can be reduced to as low as one percent. UNAIDS estimate that 430,000 children were infected worldwide in 2008 (19% of all new infections), primarily by this route, and that a further 65,000 infections were averted through the provision of antiretroviral prophylaxis to HIV-positive women.

Multiple infection

Unlike some other viruses, infection with HIV does not provide immunity against additional infections, particularly in the case of more genetically distant viruses. Both inter- and intra-clade multiple infections have been reported, and even associated with more rapid disease progression. Multiple infections are divided into two categories depending on the timing of the acquisition of the second strain. Coinfection refers to two strains that appear to have been acquired at the same time (or too close to distinguish). Reinfection (or superinfection) is infection with a second strain at a measurable time after the first. Both forms of dual infection have been reported for HIV in both acute and chronic infection around the world.

Virology

Structure and genome

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.

Replication cycle

Entry to the cell

HIV 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 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) 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.

Replication and transcription

Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the 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. This means that those cells most likely to be killed by HIV are those currently fighting infection.

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).

Assembly and release

The final step of the viral cycle, assembly of new HIV-1 virons, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi complex where it is cleaved by protease and processed into the two HIV envelope glycoproteins gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors the 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. Maturation either occurs in the forming bud or in the immature virion after it buds from the host cell. During maturation, HIV proteases cleave the polyproteins into individual functional HIV proteins and enzymes. The various structural components then assemble to produce a mature HIV virion. This cleavage step can be inhibited by protease inhibitors. The mature virus is then able to infect another cell.

Genetic variability

of the SIV and HIV.]] 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. 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.

Treatment

– a nucleoside analog reverse transcriptase inhibitors (NARTIs or NRTIs)]]

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.

Other treatments being researched

Stem cell transplantation

In 2007, an 40-year-old HIV positive patient was given a stem cell transplant as part of their treatment for acute myelogenous leukemia (AML). The bone marrow used was chosen for being homozygous for a CCR5-Δ32 mutation that confers resistance HIV infection. After 600 days without antiretroviral drug treatment, HIV levels in the person's blood, bone marrow and bowel were below the limit of detection, though it was suspected that the virus was still present in other tissues. The treatment is not considered a a possible cure because of its anecdotal nature, the mortality risk associated with bone marrow transplants and other concerns.

Banlec

In 2010, a chemical called BanLec was reported to be a potent inhibitor of HIV replication. Researchers found that BanLec bound to the HIV-1 envelope protein gp120, which is high in sugar content, inhibiting viral entry into human cells. BanLec is not FDA approved for the treatment of HIV-1 infection and it should not be used to treat or prevent HIV-1 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.

Virus entry inhibitors

In December 2010, an experimental treatment with a peptide – similar to a protein but shorter – called VIR-576, was reported, that may stop the HIV virus from “docking” with a human cell. A small clinical trial showed a 95 percent reduction in the amount of HIV in patients' blood, but with a treatment requiring expensive and regular injections.

Prognosis

Without treatment, the net median survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype, and the median survival rate after diagnosis of AIDS in resource-limited settings where treatment is not available ranges between 6 and 19 months, depending on the study. In areas where it is widely available, the development of HAART as effective therapy for HIV infection and AIDS reduced the death rate from this disease by 80%, and raised the life expectancy for a newly diagnosed HIV-infected person to 20–50 years.

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,

Epidemiology

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.

History

Origins

:See History of known cases and spread for early cases of HIV / AIDS HIV is thought to have originated in non-human primates in sub-Saharan Africa and was transferred to humans late in the 19^th or early in the 20^th century. The first paper recognizing a pattern of opportunistic infections characteristic of AIDS was published in 1981.

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 19^th—early 20^th 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

Discovery

AIDS was first clinically observed between late 1980 and early 1981. Injection drug users and gay men with no known cause of impaired immunity showed symptoms of Pneumocystis carinii pneumonia (PCP), a rare opportunistic infection that was known to present itself 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 PCP and KS quickly emerged, alerting U.S. Centers for Disease Control and Prevention (CDC). A CDC task force was formed to monitor the outbreak. After recognizing a pattern of anomalous symptoms presenting themselves in patients, the task force named the condition acquired immune deficiency syndrome (AIDS).

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."

AIDS denialism

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.

References

External links

Category:HIV/AIDS Category:Lentiviruses Category:Sexually transmitted diseases and infections Category:Immunodeficiency Category:Discovery and invention controversies Category:Initialisms Category:Causes of death

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.

Early life

Fry was born in Hampstead, London, on 24 August 1957, the son of Marianne Eve Fry (née Newman) and Alan John Fry, who was an English physicist and inventor. His maternal grandparents, Martin and Rosa Neumann, and his mother's aunt and cousins died in Auschwitz. before going on to Stouts Hill Preparatory School at the age of seven, and then to Uppingham School, Rutland, where he joined Fircroft house. He was expelled from Uppingham when he was 15, and subsequently from Paston School.

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.

Career

Television

, Regent Street, London on 3 February 2009]] Fry's career in television began with the 1982 broadcasting of The Cellar Tapes, the 1981 Cambridge Footlights Revue which was written by Fry, Hugh Laurie, Emma Thompson and Tony Slattery. The revue caught the attention of Granada Television, who, keen to replicate the success of the BBC's Not the Nine O'Clock News, hired Fry, Laurie and Thompson to star alongside Ben Elton in There's Nothing to Worry About!. A second series, re-titled Alfresco, was broadcast in 1983 and a third in 1984; it established Fry and Laurie's reputation as a comedy double act. In 1983, the BBC offered them their own show, which became The Crystal Cube, a mixture of science fiction and mockumentary that was axed after the first episode. Undeterred, Fry and Laurie appeared in an episode of The Young Ones in 1984, and Fry in Ben Elton's 1985 series, Happy Families. In 1986 and 1987 Fry and Laurie also performed sketches on the LWT/Channel 4 show Saturday Live.

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.

QI

In 2003, he began hosting the TV panel game QI. In 2006, he won the Rose d'Or award for "Best Game Show Host" for his work on the series.

Other series

A foray into documentary-making has seen Fry fronting the Emmy Award-winning The Secret Life of the Manic Depressive in 2006, and in 2007 a documentary on the subject of HIV and AIDS, HIV and Me. Also in 2006, he appeared in the genealogy series Who Do You Think You Are?, tracing his family tree to discover his Slovak Jewish ancestry. His six-part travel series Stephen Fry in America began on BBC One on 12 October 2008. A five-part companion series, More Fry in America, has been commissioned for BBC Four; it will feature in-depth essays that Fry could not include in the original programmes because of time constraints.

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.

Film

Having made his film debut in the 1985 film The Good Father, Fry had a brief appearance in A Fish Called Wanda (in which he is knocked out by Kevin Kline, who is posing as an airport security man) and then appeared in the lead role for Kenneth Branagh's Peter's Friends in 1992. In the 1994 romantic comedy film I.Q., he played the role of James Moreland. Portraying Oscar Wilde (a man of whom he had been a fan since the age of 13) in the 1997 film Wilde, he fulfilled to critical acclaim a role that he has said he was "born to play". In 2001, he played the detective in Robert Altman's period costume drama, Gosford Park. In the same year he also appeared in the Dutch film The Discovery of Heaven, directed by Jeroen Krabbé and based on the novel by Harry Mulisch.

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.

Radio

Fry came to the attention of radio listeners with the 1986 creation of his supposed alter-ego, Donald Trefusis, whose "wireless essays" were broadcast on the BBC Radio 4 programme Loose Ends. In the 1980s he starred as David Lander in four series of the BBC Radio 4 show Delve Special, written by Tony Sarchet, which became a six part Channel 4 series This is David Lander in 1988. In 1988, Fry wrote and presented a six-part comedy series entitled Saturday Night Fry; frequent radio appearances have ensued (notably on panel games Just a Minute and I'm Sorry I Haven't a Clue). In 2000, he began starring as Charles Prentiss in the Radio 4 comedy Absolute Power, reprising the role for three further series on radio and two on television. In 2002, Fry voiced Winnie-the-Pooh and was one of the narrators in Winnie-the-Pooh and The House at Pooh Corner, both written by A.A Milne. He presented a weekly, 20 x 120-minute series, "The Incomplete and Utter History of Classical Music", a 'witty guide' to the genre over the past 1,000 years, on Classic FM.

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.

Theatre

Fry wrote a play entitled Latin! (or Tobacco and Boys) for the 1980 Edinburgh Festival, where it won the "Fringe First" prize. It had a revival in 2009 at London's Cock Tavern Theatre, directed by Adam Spreadbury-Maher. The Cellar Tapes, the Footlights Revue of 1981, won the Perrier Comedy Award. In 1984, Fry adapted the hugely successful 1930s musical, Me and My Girl, for the West End, where it ran for eight years. He was also cast in a lead role in Simon Gray's 1995 play, Cell Mates, which he left three days into the West End run, pleading stage fright. He later recalled the incident as a hypomanic episode in his documentary on bipolar disorder. In 2007, Fry wrote a Christmas pantomime, Cinderella, which ran at London's Old Vic Theatre. Fry is a long-time fan of the 1960s anarchic British musical comedy group, the Bonzo Dog Band and, particularly, of its eccentric front man, the late Vivian Stanshall. Fry helped to fund an ill-fated 1988 London re-staging of the Stanshall's acclaimed Stinkfoot, a Comic Opera, written by Vivian and Ki Longfellow-Stanshall for the Bristol-based Old Profanity Showboat. Fry performed several of Stanshall's numbers as part of the Bonzo's 26 January 2006 reunion concert at the London Astoria. He also appears as a shiny New Millennium Bonzo on their post-reunion album, Pour l'Amour des Chiens, including his reciting of a recipe for "Salmon Proust", playing a butler in "Hawkeye the Gnu", and voicing ads for the fictitious "Fiasco" stores.

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.

Audio books

Stephen Fry has been the reader for the British versions of all of J.K.Rowling's Harry Potter series of audio books. He discussed this project in an interview with J.K. Rowling in 2005. Fry has also been the reader for Douglas Adams's The Hitchhiker's Guide To The Galaxy film tie-in edition. He has also made recordings of his own books, such as The Stars' Tennis Balls; and works by Roald Dahl, Michael Bond, A. A. Milne, and Anthony Buckeridge.

Video games

Fry's distinctive voice has been featured in a number of video games, including an appearance as Reaver, a main character in Lionhead Studios games Fable II and Fable III, and as the narrator in LittleBigPlanet on PlayStation 3 and PlayStation Portable. He also served as narrator on the first four Harry Potter games (Philosopher's Stone, Chamber of Secrets, Prisoner of Azkaban and the Goblet of Fire). He will return to voice his role as the narrator in LittleBigPlanet 2 in 2011.

Advertisements

Fry has lent himself and his voice to many advertisements, for companies and products such as Marks and Spencer, Twinings, Kenco, Vauxhall, Direct Line, Calpol, Heineken, Alliance & Leicester, After Eights and Orange Mobile.

Literature

Since the publication of his first novel, The Liar (1991), Fry has written three additional novels, several non-fiction works and two volumes of autobiography. Making History (1997) is partly set in an alternative universe where Adolf Hitler's father is made infertile and his replacement proves a rather more effective Führer. The book won the Sidewise Award for Alternate History. The Hippopotamus (1994) centres around Edward (Ted/Tedward) Wallace and his stay at his old friend Lord Logan's country manor in Norfolk. The Stars' Tennis Balls (2000) is a modern retelling of The Count of Monte Cristo. Fry's book, , is a guide to writing poetry.

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.

Football

On 13 August 2010, Fry joined the Board of Directors at Norwich City Football Club. He is frequently asked to promote various charities and causes, often inadvertently causing his website to crash because of the sheer volume of traffic generated by his large number of followers, as Fry notes on his website: "Four thousand hits a second all diving down the pipeline at the same time for minutes on end." Fry uses his influence to recommend underexposed musicians and authors (which often see large increases in web hits and sales) and to spread contemporary issues in the world of media and politics, notably the dropping of an injunction against The Guardian and the lambasting of Daily Mail columnist Jan Moir over her article on deceased Boyzone member Stephen Gately.

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.

Acclaim

In 1995, Fry was presented with an honorary doctorate from the University of Dundee, which named their main Students' Association bar after his novel The Liar. Fry is a patron of its Lip Theatre Company. He also served two consecutive terms—1992 to 1995 and 1995 to 1998—as the student-elected Rector of the University of Dundee. He was awarded the AoC Gold Award in 2004, and was entered into their hall of fame. Fry was also awarded an honorary degree from Anglia Ruskin University of Cambridge, England in 2005. and was also made honorary president of the Cambridge University Quiz Society and honorary fellow of Queens' College, Cambridge. He is a Patron of the Norwich Playhouse theatre and a Vice President of The Noël Coward Society. Fry was the last person to be named Pipe Smoker of the Year before the award was discontinued. On 13 July 2010, he was made an honorary fellow of Cardiff University.

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.

Views on religion

Fry has repeatedly expressed opposition to organised religion and has identified himself as an atheist, while declaring some sympathy for ancient Greek belief in capricious gods. In his first autobiography he wrote, "I knew I couldn't believe in God, because I was fundamentally Hellenic in my outlook." He has accepted that religion can have positive effects, "Sometimes belief means credulity, sometimes an expression of faith and hope which even the most sceptical atheist such as myself cannot but find inspiring." In 2009 he and Christopher Hitchens participated in an 'Intelligence Squared' debate in which they argued against Ann Widdecombe and Archbishop John Onaiyekan, who supported the view that the Catholic Church was a force for good. Fry and Hitchens argued that the church did more harm than good. Fry attacked the Catholic Church's teachings on sexuality and denounced its wealth.

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.

Personal life

Fry struggled to keep his homosexuality secret during his teenage years at public school, and has claimed not to have engaged in sexual activity for 16 years from 1979 until 1995. When asked when he first acknowledged his sexuality, Fry quipped: "I suppose it all began when I came out of the womb. I looked back up at my mother and thought to myself, 'That's the last time I'm going up one of those.'" Fry was in a 14-year relationship with his former partner, Daniel Cohen, which ended in 2010. Fry has a home in London and in Hollywood. He also has a home near King's Lynn, Norfolk. When in London, Fry drives a black TX4 London cab.

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.".

Poland controversy

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

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

Lara Roxx is the stage name of a Montreal, Quebec-born Canadian porn actress who, in March 2004, became the first known individual in four years to allegedly contract HIV while making a US porn video.

Career

Roxx became famous at age 21, after being exposed to HIV while doing a pornographic scene with Darren James. She allegedly contracted the disease just two months after doing her first scene, a double anal. Roxx said previously that she relied on the industry's HIV standards to ensure her safety.

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.

References

External links

Porn Faces Reality; at the Village Voice

Post-porn plans; at the Montreal Mirror

Interview at lukeisback.com

Video at YouTube

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)