163-542: The Treatment Action Campaign ( TAC ) is a South African HIV/AIDS activist organisation which was co-founded by the HIV-positive activist Zackie Achmat in 1998. TAC is rooted in the experiences, direct action tactics and anti-apartheid background of its founder. TAC has been credited with forcing the reluctant government of former South African President Thabo Mbeki to begin making antiretroviral drugs available to South Africans. The Treatment Action Campaign (TAC)
326-490: A long terminal repeat (LTR). Regions in the LTR act as switches to control production of new viruses and can be triggered by proteins from either HIV or the host cell. The Psi element is involved in viral genome packaging and recognized by gag and rev proteins. The SLIP element ( TTTTTT ) is involved in the frameshift in the gag - pol reading frame required to make functional pol . The term viral tropism refers to
489-587: A "frontline" country because of its shared border with South Africa, where the ANC was attempting to re-establish its underground. However, although he travelled frequently in subsequent years, the ANC's Lusaka headquarters remained his central base. Between 1975 and 1976, Mbeki was instrumental in establishing the ANC's frontline base in Swaziland. He was first sent there to assess the political landscape in January 1975, under
652-486: A Senator, visited TAC's Khayelitsha office and met with then TAC chairperson Zackie Achmat. During his visit, Obama emphasised the importance of HIV testing and urged the South African government to "awake" from AIDS denialism. TAC is supported by Ashoka , a nonprofit organisation that promotes social entrepreneurship. TAC has worked with and shown solidarity with a number of organisations and movements. This includes
815-812: A State of Emergency and gave the army and police special powers. In 1986, the South African Army sent a captain in the South African Defence Force (SADF) to kill Mbeki. The plan was to put a bomb in his house in Lusaka, but the assassin was arrested by the Zambian police before he could go through with the plan. In 1985, Mbeki became the ANC's director of the Department of Information and Publicity and coordinated diplomatic campaigns to involve more white South Africans in anti-apartheid activities. In 1989, he rose in
978-535: A cell by a virion can be called "cell-free spread" to distinguish it from a more recently recognized process called "cell-to-cell spread". In cell-free spread (see figure), virus particles bud from an infected T cell, enter the blood or extracellular fluid and then infect another T cell following a chance encounter. HIV can also disseminate by direct transmission from one cell to another by a process of cell-to-cell spread, for which two pathways have been described. Firstly, an infected T cell can transmit virus directly to
1141-481: A cell surface. The unusual processing and high density means that almost all broadly neutralising antibodies that have so far been identified (from a subset of patients that have been infected for many months to years) bind to, or are adapted to cope with, these envelope glycans. The molecular structure of the viral spike has now been determined by X-ray crystallography and cryogenic electron microscopy . These advances in structural biology were made possible due to
1304-702: A condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, the average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype . In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood , pre-ejaculate , semen , and vaginal fluids . Non-sexual transmission can occur from an infected mother to her infant during pregnancy , during childbirth by exposure to her blood or vaginal fluid, and through breast milk . Within these bodily fluids, HIV
1467-678: A fairly common practice, and even a rite of passage, among young people identified as belonging to the future generation of ANC and SACP political leaders. He was educated at the Lenin Institute , where, because of the secrecy required, he went by the alias "Jack Fortune." He excelled at the institute and in June 1970 was appointed to the Central Committee of the SACP, alongside Chris Hani. The last part of his training entailed military training, also
1630-414: A few tested specimens might provide inconclusive results because of a low quantity specimen. In these situations, a second specimen is collected and tested for HIV infection. Modern HIV testing is extremely accurate, when the window period is taken into consideration. A single screening test is correct more than 99% of the time. The chance of a false-positive result in a standard two-step testing protocol
1793-643: A government victory, the government showed no interest in providing access to the generic antiretroviral medications that its victory allowed. Indeed, far from embracing their common victory against the patent rights of multinational companies who were not making affordable drugs available, President Thabo Mbeki began promoting the AIDS denialist view that HIV might not cause AIDS, and that AIDS medications were more toxic than helpful, inviting foreign AIDS denialists to advise his government. According to TAC's founder, two million South Africans died prematurely of AIDS during
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#17328479223451956-503: A hotel in Switzerland . Known as "Operation Flair", PW Botha was kept informed of all the meetings. At the same time, Mandela and Kobie Coetzee , the Minister of Justice, were also holding secret talks. When Mbeki finally was able to return home to South Africa and was reunited with his own father, the elder Mbeki told a reporter, "You must remember that Thabo Mbeki is no longer my son. He
2119-448: A human host cell when the newly formed virus particle buds from the cell. The viral envelope contains proteins from the host cell and relatively few copies of the HIV envelope protein, which consists of a cap made of three molecules known as glycoprotein (gp) 120 , and a stem consisting of three gp41 molecules that anchor the structure into the viral envelope. The envelope protein, encoded by
2282-568: A key step in the progression to AIDS. A number of studies with subtype B-infected individuals have determined that between 40 and 50 percent of AIDS patients can harbour viruses of the SI and, it is presumed, the X4 phenotypes. HIV-2 is much less pathogenic than HIV-1 and is restricted in its worldwide distribution to West Africa . The adoption of "accessory genes" by HIV-2 and its more promiscuous pattern of co-receptor usage (including CD4-independence) may assist
2445-600: A more stable conformation following the NC binding, in which both the DIS and the U5:AUG regions of the gRNA participate in extensive base pairing. RNA can also be processed to produce mature messenger RNAs (mRNAs). In most cases, this processing involves RNA splicing to produce mRNAs that are shorter than the full-length genome. Which part of the RNA is removed during RNA splicing determines which of
2608-419: A narrowing budget deficit , and consistent, moderate economic growth. However, despite his retention of various social democratic programmes, and notable expansions to the black economic empowerment programme, critics often regarded Mbeki's economic policies as neoliberal , with insufficient consideration for developmental and redistributive objectives. On these grounds, Mbeki grew increasingly alienated from
2771-449: A new generation of leaders had to be prepared for succession. In the late 1980s and early 1990s, Mbeki's key role in the early negotiations made him a likely contender for top leadership positions in the party, and he was even considered to be in line for the ANC presidency. However, at the ANC's 48th National Conference in July 1991, its first national elective conference since 1960, Mbeki
2934-447: A number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4 T cells by CD8 cytotoxic lymphocytes that recognize infected cells. When CD4 T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to
3097-567: A rational expectation. — Mbeki in 1997, on filling Mandela's shoes Following the 1994 elections , South Africa's first under universal suffrage , Mbeki became one of the two national deputy presidents in the ANC-led Government of National Unity , in which Mandela was president. At the ANC's next national conference , held in December that year, Mbeki was elected unopposed to the ANC deputy presidency, also under Mandela. In June 1996,
3260-406: A rite of passage, including in intelligence, guerrilla tactics, and weaponry. However, his biographer Mark Gevisser adduces that he was "not the ideal candidate for military life," and Max Sisulu , who trained alongside him, says that he always regarded Mbeki as better suited to political leadership than military leadership. In April 1971, having been pulled out from military training, Mbeki
3423-741: A role in African and global politics that was disproportionate to the country's size and historical influence. He was the central architect of the New Partnership for Africa's Development and, as the inaugural chairperson of the African Union , spearheaded the introduction of the African Peer Review Mechanism . After the IBSA Dialogue Forum was launched in 2003, his government collaborated with India and Brazil to lobby for reforms at
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#17328479223453586-469: A small group of Cape Town activists, a number of whom had political roots in the Marxist Workers Tendency of the ANC , TAC became a much more broadly based group, with chapters in many regions of the nation and a largely black and poor constituency. The group campaigns for greater access to HIV treatment for all South Africans by raising public awareness and understanding about issues surrounding
3749-460: A strain of SIV found in sooty mangabees. Since HIV-1 is derived from SIVcpz, and HIV-2 from SIVsm, the genetic sequence of HIV-2 is only partially homologous to HIV-1 and more closely resembles that of SIVsm. Many HIV-positive people are unaware that they are infected with the virus. For example, in 2001 less than 1% of the sexually active urban population in Africa had been tested, and this proportion
3912-558: A target T cell via a virological synapse . Secondly, an antigen-presenting cell (APC), such as a macrophage or dendritic cell, can transmit HIV to T cells by a process that either involves productive infection (in the case of macrophages) or capture and transfer of virions in trans (in the case of dendritic cells). Whichever pathway is used, infection by cell-to-cell transfer is reported to be much more efficient than cell-free virus spread. A number of factors contribute to this increased efficiency, including polarised virus budding towards
4075-478: A top-level strategic meeting in Luanda , Angola, when Maharaj, who had been tasked with running the political underground, claimed that Mbeki's records from the Swaziland office were in fact "just an empty folder." After being deported, Mbeki returned to Lusaka, where he was made Duma Nokwe's deputy in the ANC's Department of Information and Propaganda (DIP). In January 1977, he was posted to Lagos , Nigeria, where he
4238-649: A touring football team, and then in Rhodesia . He arrived at the ANC's new headquarters in Dar es Salaam , Tanzania, in November 1962, and left shortly afterwards for England. While at Sussex, Mbeki was involved in ANC work and in broader organising for the English Anti-Apartheid Movement . Months after his arrival, his father was arrested during a Security Branch raid at Liliesleaf Farm in July 1963. During
4401-801: A two-year term. Controversially, in February 2007, South Africa followed Russia and China in voting against a draft resolution calling for an end to political detentions and military attacks against ethnic minorities in Myanmar. Mbeki later told the media that the resolution exceeded the Security Council's mandate, and that its tabling had been illegal in terms of international law . Mbeki's presidency coincided with an escalating political and economic crisis in South Africa's neighbour, Zimbabwe, under president Mugabe of ZANU-PF. Problems included land invasions under
4564-456: Is an adaptation for repair of genome damage, and that recombinational variation is a byproduct that may provide a separate benefit. The final step of the viral cycle, assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi apparatus where it is cleaved by furin resulting in
4727-507: Is bound with the CD4 protein, the envelope complex undergoes a structural change, exposing the chemokine receptor binding domains of gp120 and allowing them to interact with the target chemokine receptor. This allows for a more stable two-pronged attachment, which allows the N-terminal fusion peptide gp41 to penetrate the cell membrane. Repeat sequences in gp41, HR1, and HR2 then interact, causing
4890-423: Is estimated to be about 1 in 250,000 in a low risk population. Testing post-exposure is recommended immediately and then at six weeks, three months, and six months. Thabo Mbeki Thabo Mvuyelwa Mbeki ( Xhosa: [tʰaɓɔ ʼmbɛːki] ; born 18 June 1942) is a South African politician who served as the 2nd democratic president of South Africa from 14 June 1999 to 24 September 2008, when he resigned at
5053-424: Is even lower in rural populations. Furthermore, in 2001 only 0.5% of pregnant women attending urban health facilities were counselled, tested or received their test results. Again, this proportion is even lower in rural health facilities. Since donors may therefore be unaware of their infection, donor blood and blood products used in medicine and medical research are routinely screened for HIV. HIV-1 testing
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5216-464: Is high as the glycans shield the underlying viral protein from neutralisation by antibodies. This is one of the most densely glycosylated molecules known and the density is sufficiently high to prevent the normal maturation process of glycans during biogenesis in the endoplasmic and Golgi apparatus. The majority of the glycans are therefore stalled as immature 'high-mannose' glycans not normally present on human glycoproteins that are secreted or present on
5379-399: Is initially done using an enzyme-linked immunosorbent assay (ELISA) to detect antibodies to HIV-1. Specimens with a non-reactive result from the initial ELISA are considered HIV-negative, unless new exposure to an infected partner or partner of unknown HIV status has occurred. Specimens with a reactive ELISA result are retested in duplicate. If the result of either duplicate test is reactive,
5542-447: Is largely confined to West Africa . HIV is similar in structure to other retroviruses. It is roughly spherical with a diameter of about 120 nm , around 100,000 times smaller in volume than a red blood cell . It is composed of two copies of positive- sense single-stranded RNA that codes for the virus' nine genes enclosed by a conical capsid composed of 2,000 copies of the viral protein p24 . The single-stranded RNA
5705-601: Is more likely, leading to immunodeficiency. Three groups of HIV-1 have been identified on the basis of differences in the envelope ( env ) region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes (or clades ), based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in
5868-522: Is my comrade!" A news article pointed out that this was an expression of pride, explaining, "For Govan Mbeki, a son was a mere biological appendage; to be called a comrade, on the other hand, was the highest honour." In the late 1970s, Mbeki made a number of trips to the United States in search of support among US corporations. Literate and funny, he made a wide circle of friends in New York City. Mbeki
6031-555: Is present as both free virus particles and virus within infected immune cells . Research has shown (for both same-sex and opposite-sex couples) that HIV is not contagious during sexual intercourse without a condom if the HIV-positive partner has a consistently undetectable viral load . HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4 T cells), macrophages , and dendritic cells . HIV infection leads to low levels of CD4 T cells through
6194-459: Is safely held." Mbeki said in 2004: ...the critical role we should play is to assist the Zimbabweans to find each other, really to agree among themselves about the political, economic, social, other solutions that their country needs. We could have stepped aside from that task and then shouted, and that would be the end of our contribution... They would shout back at us and that would be the end of
6357-412: Is tightly bound to nucleocapsid proteins, p7, and enzymes needed for the development of the virion such as reverse transcriptase , proteases , ribonuclease and integrase . A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of the virion particle. This is, in turn, surrounded by the viral envelope , that is composed of the lipid bilayer taken from the membrane of
6520-534: Is unknown how often such mixed packaging occurs under natural conditions. Bonhoeffer et al. suggested that template switching by reverse transcriptase acts as a repair process to deal with breaks in the single-stranded RNA genome. In addition, Hu and Temin suggested that recombination is an adaptation for repair of damage in the RNA genomes. Strand switching (copy-choice recombination) by reverse transcriptase could generate an undamaged copy of genomic DNA from two damaged single-stranded RNA genome copies. This view of
6683-593: The "fast-track" land reform programme, political violence and state-sponsored human rights violations, and hyperinflation . With SADC's endorsement, Mbeki frequently acted as a mediator between ZANU-PF and the Zimbabwean opposition. However, controversially, his policy towards the Mugabe regime was one of non-confrontational "quiet diplomacy" and "constructive engagement": he refused to condemn Mugabe and instead attempted to persuade him to accept gradual political reforms. He
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6846-454: The AIDS denialist position, as did his Minister of Health, Manto Tshabalala-Msimang . The Minister of Health put special emphasis on nutrition as an alternative to antiretroviral treatment. As the top health official of South Africa, she was a particular target of TAC activism. Tshabalala-Msimang was removed as Health Minister in September 2008 after President Mbeki left office, a move hailed by
7009-663: The African National Congress (ANC) and the South African Communist Party (SACP). Both Epainette and Govan came from educated, Christian , land-owning families, and Govan's father was Sikelewu Mbeki, a colonially appointed headman . The couple had met in Durban , where Epainette had become the second black woman to join the SACP (then still called the Communist Party of South Africa). However, while Mbeki
7172-712: The African Union (AU), of which he became the inaugural chairperson in 2002, and his government spearheaded the introduction of the AU's African Peer Review Mechanism in 2003. He was twice chairperson of the Southern African Development Community (SADC), first from 1999 to 2000 and second, briefly, in 2008. Through these multilateral organisations and by contributing forces to various United Nations (UN) peacekeeping missions, Mbeki and his government were involved in peacekeeping initiatives in African countries including Zimbabwe, Ethiopia and Eritrea, Liberia,
7335-633: The African green monkey (SIVagm) and sooty mangabey (SIVsmm) are thought to have a long evolutionary history with their hosts. These hosts have adapted to the presence of the virus, which is present at high levels in the host's blood, but evokes only a mild immune response, does not cause the development of simian AIDS, and does not undergo the extensive mutation and recombination typical of HIV infection in humans. In contrast, when these strains infect species that have not adapted to SIV ("heterologous" or similar hosts such as rhesus or cynomologus macaques ),
7498-541: The CCR5-Δ32 mutation are resistant to infection by the R5 virus, as the mutation leaves HIV unable to bind to this co-receptor, reducing its ability to infect target cells. Sexual intercourse is the major mode of HIV transmission. Both X4 and R5 HIV are present in the seminal fluid , which enables the virus to be transmitted from a male to his sexual partner . The virions can then infect numerous cellular targets and disseminate into
7661-606: The Cato Institute commended Mbeki's macroeconomic policies, which reduced the budget deficit and public debt and which according to them likely played a role in increasing economic growth. According to the Free Market Foundation , during the Mbeki presidency, average annualised quarter-on-quarter GDP growth was 4.2%, and average annual inflation was 5.7%. On the other hand, the shift alienated leftists, including inside in
7824-549: The Growth, Employment and Redistribution (GEAR) programme, which was introduced in 1996 and remained a cornerstone of Mbeki's administration after 1999. In comparison to the Reconstruction and Development Programme policy which had been the basis of the ANC's platform in 1994, GEAR placed less emphasis on developmental and redistributive imperatives, and subscribed to elements of the liberalisation, deregulation, and privatisation at
7987-853: The National Party withdrew from the Government of National Unity and, with the second deputy, de Klerk, having thereby resigned, Mbeki became the sole deputy president. The same year, as deputy president, Mbeki acted as a peace broker in what was then known as Zaire , following the First Congo War and the deposition of Zairean president Mobutu Sese Seko . Mbeki also took on increasing domestic responsibilities, including executive powers delegated to him by Mandela, to such an extent that Mandela called him "a de facto president." Mandela had made it clear publicly since early 1995 or earlier that he intended to retire after one term in office, and by then Mbeki
8150-660: The Social Justice Coalition , the Anti-Eviction Campaign , the AIDS Law Project and COSATU . In October 2009, TAC issued a statement of Solidarity with Abahlali baseMjondolo condemning the attacks by ANC members on Kennedy Road informal settlement . HIV The human immunodeficiency viruses ( HIV ) are two species of Lentivirus (a subgroup of retrovirus ) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS),
8313-592: The United Nations , advocating for a stronger role for developing countries. Among South Africa's various peacekeeping commitments during his presidency, Mbeki was the primary mediator in the conflict between ZANU-PF and the Zimbabwean opposition in the 2000s. However, he was frequently criticised for his policy of "quiet diplomacy" in Zimbabwe, under which he refused to condemn Robert Mugabe 's regime or institute sanctions against it. Also highly controversial worldwide
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#17328479223458476-445: The adsorption of glycoproteins on its surface to receptors on the target cell followed by fusion of the viral envelope with the target cell membrane and the release of the HIV capsid into the cell. Entry to the cell begins through interaction of the trimeric envelope complex ( gp160 spike) on the HIV viral envelope and both CD4 and a chemokine co-receptor (generally either CCR5 or CXCR4 , but others are known to interact) on
8639-421: The gag polyproteins still need to be cleaved into the actual matrix, capsid and nucleocapsid proteins. This cleavage is mediated by the packaged viral protease and can be inhibited by antiretroviral drugs of the protease inhibitor class. The various structural components then assemble to produce a mature HIV virion. Only mature virions are then able to infect another cell. The classical process of infection of
8802-514: The microtubule -based transport to the nucleus, the viral single-strand RNA genome is transcribed into double-strand DNA, which is then integrated into a host chromosome. HIV can infect dendritic cells (DCs) by this CD4-CCR5 route, but another route using mannose-specific C-type lectin receptors such as DC-SIGN can also be used. DCs are one of the first cells encountered by the virus during sexual transmission. They are currently thought to play an important role by transmitting HIV to T cells when
8965-403: The phylogenetic tree representing the lineage of the M group of HIV-1. Co-infection with distinct subtypes gives rise to circulating recombinant forms (CRFs). In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and
9128-617: The propaganda section of the ANC's English headquarters. He remained active in the SACP, which was very closely allied to the ANC, and in 1967 he was appointed to the editorial board of its official magazine, the African Communist . Throughout his time in England, Mbeki was the ward of O. R. Tambo and his wife Adelaide Tambo – in the absence of his parents, it was Adelaide and senior communist Michael Harmel who attended Mbeki's graduation ceremony in 1965. O. R. Tambo later became
9291-414: The right to health care , and the government was ordered to provide MTCT programs in public clinics. TAC also assisted the government by defending it in the case brought against the government by the pharmaceutical industry . TAC entered the case as an amicus curiae , submitting a brief in favour of the government's position. Although the withdrawal of the pharmaceutical companies from this case resulted in
9454-438: The α -chemokine receptor, CXCR4 , for entry. Dual-tropic HIV-1 strains are thought to be transitional strains of HIV-1 and thus are able to use both CCR5 and CXCR4 as co-receptors for viral entry. The α -chemokine SDF-1 , a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down-regulating the expression of CXCR4 on the surface of HIV target cells. M-tropic HIV-1 isolates that use only
9617-427: The β -chemokine receptor, CCR5 , for entry and are thus able to replicate in both macrophages and CD4 T cells. This CCR5 co-receptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV infection. They appear to be the first cells infected by HIV and perhaps the source of HIV production when CD4 cells become depleted in
9780-482: The "seminal thinker" behind NEPAD and its "principal author and articulator." According to academic Chris Landsberg, NEPAD's central principle – "African leaders holding one another accountable in exchange for the recommitment of the industrialised world to Africa's development" – epitomised Mbeki's strategy in Africa. Mbeki was also involved in the dissolution of the Organisation of African Unity and its replacement by
9943-482: The ANC and its Tripartite Alliance . Zwelinzima Vavi of the Congress of South African Trade Unions (COSATU) was an outspoken critic of Mbeki's "market-friendly" economic policies, claiming that Mbeki's "flirtation" with neoliberalism had been "absolutely disastrous" for development, and especially for the labour-intensive development required to address South Africa's high unemployment rate. The discord between Mbeki and
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#173284792234510106-528: The ANC and other political organisations would be unbanned, and ANC exiles began to return to South Africa. At the same time that it was to negotiate the end of apartheid , the ANC had to implement a significant internal reorganisation, absorbing into its official exile bodies the domestic ANC underground, released political prisoners, and other activists from the trade unions and the United Democratic Front . It also had an ageing leadership, meaning that
10269-440: The ANC was unbanned in 1990. He rose through the organisation in its information and publicity section and as Oliver Tambo 's protégé, but he was also an experienced diplomat, serving as the ANC's official representative in several of its African outposts. He was an early advocate for and leader of the diplomatic engagements which led to the negotiations to end apartheid . After South Africa's first democratic elections in 1994, he
10432-485: The ANC won by a significant majority, Mbeki was elected president of South Africa . He was re-elected for a second term in 2002. Ours is a capitalist society. It is therefore inevitable that, in part – and I repeat, in part – we must address this goal of deracialisation within the context of the property relations characteristic [of] a capitalist economy. — Mbeki in 1999 Mbeki had been highly involved in economic policy as deputy president, especially in spearheading
10595-804: The ANC's leadership. Over the next three years, Ramaphosa also came to eclipse Mbeki as the party's central negotiator when he, not Mbeki, was appointed to lead the ANC's delegation to the CODESA talks. Once SACP leader Chris Hani was assassinated in April 1993, Ramaphosa became Mbeki's primary competition in the ANC succession battle. When Tambo died later the same month, Mbeki succeeded him as ANC national chairperson. Well, I don't imagine that there's any such requirement. I mean, he's got very big feet. The shoes will be too big. What does that mean? Does it mean we start off by going to jail for 27 years and then sort of graduate from there, grow taller, wear strange shirts? It's not
10758-480: The ANC's longest-serving president, and he acted as Mbeki's "political mentor and patron" until his death in 1993. Other friends Mbeki made in England, including Ronnie Kasrils and brothers Essop Pahad and Aziz Pahad , were also among his key political allies in his later career. In February 1969, Mbeki was sent to Moscow in the Soviet Union to receive Marxist–Leninist political and ideological training –
10921-519: The ANC. Mbeki joined the ANC Youth League at age fourteen and in 1958 became the secretary of its Lovedale branch. Shortly afterwards, at the start of his final year of high school, he was identified as one of the leaders of a March 1959 boycott of classes, and was summarily expelled from Lovedale. He nonetheless sat for matric examinations and obtained a second-class pass. In June 1960, Mbeki moved to Johannesburg , where he lived in
11084-480: The ANC. The agreement allowed the ANC to open an office in Zimbabwe and to move MK weapons and cadres over Zimbabwean borders; moreover, it committed the Zimbabwean military to assisting the ANC, and the government to providing MK cadres with Zimbabwean identity documents. However, Mbeki handed the running of the Salisbury office over to another ANC official, and the deal later collapsed. In 1985, PW Botha declared
11247-558: The African continent. Simultaneously, however, he argued for increased developmental aid to Africa. He called for Western leaders to address global apartheid and unequal development, most memorably in a speech to the World Summit on Sustainable Development in Johannesburg in August 2002. Although Mbeki also forged strategic individual relationships with key African leaders, especially
11410-583: The CCR5 receptor are termed R5; those that use only CXCR4 are termed X4, and those that use both, X4R5. However, the use of co-receptors alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection and HIV can also infect a subtype of myeloid dendritic cells , which probably constitute a reservoir that maintains infection when CD4 T cell numbers have declined to extremely low levels. Some people are resistant to certain strains of HIV. For example, people with
11573-603: The Congress, and before the civil disobedience campaign resumed, the Cabinet voted to begin roll-out of antiretroviral access through public-sector health clinics. In the South African system, the Cabinet can overrule the President, and it appeared to have done so in this case. Although the Cabinet voted to reaffirm that South African AIDS policy is based on the evidence that HIV causes AIDS, former President Thabo Mbeki continued to support
11736-405: The DIS (dimerization initiation signal) hairpin is exposed. The formation of the gRNA dimer is mediated by a 'kissing' interaction between the DIS hairpin loops of the gRNA monomers. At the same time, certain guanosine residues in the gRNA are made available for binding of the nucleocapsid (NC) protein leading to the subsequent virion assembly. The labile gRNA dimer has been also reported to achieve
11899-615: The Democratic Republic of Congo, and Burundi. Outside Africa, Mbeki was the chairperson of the Non-Aligned Movement between 1999 and 2003 and the chairperson of the Group of 77 + China in 2006. He also pursued South -South solidarity in a coalition with India and Brazil under the IBSA Dialogue Forum , which was launched in June 2003 and held its first summit in September 2006. The IBSA countries together pressed for changes in
12062-419: The HIV env gene, allows the virus to attach to target cells and fuse the viral envelope with the target cell's membrane releasing the viral contents into the cell and initiating the infectious cycle. As the sole viral protein on the surface of the virus, the envelope protein is a major target for HIV vaccine efforts. Over half of the mass of the trimeric envelope spike is N-linked glycans . The density
12225-441: The HIV protein-coding sequences is translated. Mature HIV mRNAs are exported from the nucleus into the cytoplasm , where they are translated to produce HIV proteins, including Rev . As the newly produced Rev protein is produced it moves to the nucleus, where it binds to full-length, unspliced copies of virus RNAs and allows them to leave the nucleus. Some of these full-length RNAs function as mRNAs that are translated to produce
12388-570: The HIV virological synapse in vivo . The many dissemination mechanisms available to HIV contribute to the virus' ongoing replication in spite of anti-retroviral therapies. HIV differs from many viruses in that it has very high genetic variability . This diversity is a result of its fast replication cycle , with the generation of about 10 virions every day, coupled with a high mutation rate of approximately 3 x 10 per nucleotide base per cycle of replication and recombinogenic properties of reverse transcriptase. This complex scenario leads to
12551-516: The LTR promoter acting by binding the TAR RNA element. The TAR may also be processed into microRNAs that regulate the apoptosis genes ERCC1 and IER3 . The rev protein (p19) is involved in shuttling RNAs from the nucleus and the cytoplasm by binding to the RRE RNA element. The vif protein (p23) prevents the action of APOBEC3G (a cellular protein that deaminates cytidine to uridine in
12714-460: The SACP. Thus the ANC instructed him to join the growing cohort of cadres who were leaving South Africa to evade police attention, receive training, and establish the overt ANC structures that were now illegal inside the country. Mbeki was detained twice by the police while attempting to leave the country, first in Rustenberg , when the group he was travelling with failed to pass themselves off as
12877-490: The South African government's booth in the exhibitor's area. The booth contained bowls of lemons and garlic , which the Health Minister has claimed contribute to fighting HIV. TAC members passed around these items mockingly, and toyi-toyied inside the booth, attracting attention to the South African government's expenditure on the elaborate booth and lack of corresponding commitment to the national treatment plan. During
13040-491: The South African government. These talks led to the unbanning of the ANC and the release of political prisoners. He also participated in many of the other important negotiations between the ANC and the government that eventually led to the democratisation of South Africa. As a sign of goodwill, de Klerk set free a few of the ANC's top leadership at the end of 1989, among them Govan Mbeki . On 2 February 1990, Botha's successor as state president, F. W. de Klerk , announced that
13203-801: The Treatment Action Campaign. Although antiretroviral access is now official policy, its implementation has been spotty. TAC continues to protest and sue the government (working with the AIDS Law Project ) in order to continue to influence the speed of and approach to the rollout. At the XVI International AIDS Society Conference in Toronto , 13–18 August 2006, TAC had a significant presence. Many TAC staff presented in seminars and chaired sessions, most prominently TAC Secretary Sipho Mthathi and Treasurer Mark Heywood. Heywood
13366-433: The U.S.: Although IFA can be used to confirm infection in these ambiguous cases, this assay is not widely used. In general, a second specimen should be collected more than a month later and retested for persons with indeterminate western blot results. Although much less commonly available, nucleic acid testing (e.g., viral RNA or proviral DNA amplification method) can also help diagnosis in certain situations. In addition,
13529-409: The adaptive benefit of recombination in HIV could explain why each HIV particle contains two complete genomes, rather than one. Furthermore, the view that recombination is a repair process implies that the benefit of repair can occur at each replication cycle, and that this benefit can be realized whether or not the two genomes differ genetically. On the view that recombination in HIV is a repair process,
13692-423: The advent of AIDS. HIV-positive patients acquire an enormously broad spectrum of opportunistic infections, which was particularly problematic prior to the onset of HAART therapies; however, the same infections are reported among HIV-infected patients examined post-mortem following the onset of antiretroviral therapies. Thus, during the course of infection, viral adaptation to the use of CXCR4 instead of CCR5 may be
13855-514: The agricultural subsidy regimes of developed countries at the 2003 World Trade Organisation conference , and also pressed for reforms at the UN which would allow developing countries a stronger role. Indeed, Mbeki had called for reform at the UN as early as 1999 and 2000. In 2007, following a prolonged diplomatic campaign, South Africa secured a non-permanent seat on the UN Security Council for
14018-403: The animals develop AIDS and the virus generates genetic diversity similar to what is seen in human HIV infection. Chimpanzee SIV (SIVcpz), the closest genetic relative of HIV-1, is associated with increased mortality and AIDS-like symptoms in its natural host. SIVcpz appears to have been transmitted relatively recently to chimpanzee and human populations, so their hosts have not yet adapted to
14181-402: The availability, affordability and use of HIV treatments. The Treatment Action Campaign produces Equal Treatment, a magazine dedicated to HIV and health issues. The TAC first confronted the South African government for not ensuring that mother-to-child transmission (MTCT) prevention was available to pregnant mothers. It won this case on the basis of the South African constitutional guarantee of
14344-498: The base. In Swaziland, he lived at Stanley Mabizela's family home in Manzini . Working with Albert Dhlomo, Mbeki was responsible for helping to re-establish underground ANC networks in the South African provinces of Natal and Transvaal , which shared a border with Swaziland. His counterpart inside South Africa was MK operative Jacob Zuma , who ran the Natal underground. According to Gevisser,
14507-480: The causal link between HIV and AIDS, he often posited a need to investigate alternate causes of and alternative treatments for AIDS, frequently suggesting that immunodeficiency was the indirect result of poverty. His political descent began at the ANC's Polokwane conference in December 2007, when he was replaced as ANC president by Zuma. His term as national president was not due to expire until June 2009, but, on 20 September 2008, he announced that he would resign at
14670-592: The cell as new virus particles that will begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was initially discovered and termed both lymphadenopathy associated virus (LAV) and human T-lymphotropic virus 3 (HTLV-III). HIV-1 is more virulent and more infective than HIV-2, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2, compared to HIV-1, implies that fewer of those exposed to HIV-2 will be infected per exposure. Due to its relatively poor capacity for transmission, HIV-2
14833-470: The cell types a virus infects. HIV can infect a variety of immune cells such as CD4 T cells , macrophages , and microglial cells . HIV-1 entry to macrophages and CD4 T cells is mediated through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells' membrane and also with chemokine co-receptors . Macrophage-tropic (M-tropic) strains of HIV-1, or non- syncytia -inducing strains (NSI; now called R5 viruses ) use
14996-602: The centre of Washington Consensus -style reforms. It was therefore viewed by some as a "policy reversal" and embrace of neoliberalism , and thus as an abandonment of the ANC's socialist principles. Mbeki also emphasised communication between government, business, and labour, establishing four working groups – for big business, black business, trade unions, and commercial agriculture – under which ministers, senior officials, and Mbeki himself met regularly with business and union leaders to build trust and explore solutions to structural economic problems. Conservative groups such as
15159-454: The collapse of the extracellular portion of gp41 into a hairpin shape. This loop structure brings the virus and cell membranes close together, allowing fusion of the membranes and subsequent entry of the viral capsid. After HIV has bound to the target cell, the HIV RNA and various enzymes, including reverse transcriptase, integrase, ribonuclease, and protease, are injected into the cell. During
15322-501: The concept of a dual or two-track economy in South Africa, with severe underdevelopment in one segment of the population, and, for example in a 2003 newsletter, argued that high growth alone would only benefit the developed segment, without significant trickle-down benefits for the rest of the population. Yet, somewhat paradoxically, he explicitly advocated state support for the creation of a black capitalist class in South Africa. The government's black economic empowerment policy, which
15485-628: The conference's closing ceremonies, United Nations Special Envoy for HIV/AIDS in Africa Stephen Lewis pointed out the failure of South Africa's response to HIV/AIDS, calling their actions more "[more] worthy of a lunatic fringe than of a concerned and compassionate state." He also announced that earlier in the morning, Zackie Achmat and 44 others had been arrested for occupying provincial offices in Cape Town in protest of government's failure to treat prisoners with anti-retrovirals, and in particular
15648-465: The cover of attending a UN conference. As part of this reconnaissance trip, he and his colleague Max Sisulu spent time with S'bu Ndebele , Max's sister Lindiwe Sisulu , and their associates in the Black Consciousness movement , which at the time was ascendent in neighbouring South Africa. Mbeki made a positive report to the ANC executive, and he was sent back to Swaziland to begin establishing
15811-447: The development of AIDS. HIV is a member of the genus Lentivirus , part of the family Retroviridae . Lentiviruses have many morphologies and biological properties in common. Many species are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period . Lentiviruses are transmitted as single-stranded , positive- sense , enveloped RNA viruses . Upon entry into
15974-577: The development of stable recombinant forms of the viral spike by the introduction of an intersubunit disulphide bond and an isoleucine to proline mutation ( radical replacement of an amino acid) in gp41. The so-called SOSIP trimers not only reproduce the antigenic properties of the native viral spike, but also display the same degree of immature glycans as presented on the native virus. Recombinant trimeric viral spikes are promising vaccine candidates as they display less non-neutralising epitopes than recombinant monomeric gp120, which act to suppress
16137-468: The early 1980s, Mbeki, Jacob Zuma and Aziz Pahad were appointed by Tambo to conduct private talks with representatives of the National Party government. Twelve meetings between the parties took place between November 1987 and May 1990, most of them held at Mells Park House , a country house near Bath in Somerset, England . By September 1989, the team secretly met with Maritz Spaarwater and Mike Louw in
16300-469: The ensuing Rivonia Trial , Mbeki appeared before the United Nations (UN) Special Committee on Apartheid and later led a student march from Brighton to London, a distance of fifty miles. At the conclusion of the trial, Govan and seven other ANC leaders, among them Nelson Mandela and Walter Sisulu , were sentenced to life imprisonment . Mbeki completed his bachelor's degree in economics in May 1965 but, at
16463-561: The exhortation of O. R. Tambo , enrolled for a Master's in economics and development instead of returning to Africa to join Umkhonto we Sizwe (MK), the ANC's armed wing. His Master's dissertation was in economic geography . In addition to this and his political organising, he developed a deep fondness for Yeats , Brecht , Shakespeare , and blues music . After completing his Master's, in October 1966 he moved to London to work full-time for
16626-431: The generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. When simultaneous infection occurs, the genome of progeny virions may be composed of RNA strands from two different strains. This hybrid virion then infects a new cell where it undergoes replication. As this happens,
16789-576: The generation of recombinational variation would be a consequence, but not the cause of, the evolution of template switching. HIV-1 infection causes chronic inflammation and production of reactive oxygen species . Thus, the HIV genome may be vulnerable to oxidative damage , including breaks in the single-stranded RNA. For HIV, as well as for viruses in general, successful infection depends on overcoming host defense strategies that often include production of genome-damaging reactive oxygen species. Thus, Michod et al. suggested that recombination by viruses
16952-552: The genetic information that is transmitted from parental to progeny genomes. Viral recombination produces genetic variation that likely contributes to the evolution of resistance to anti-retroviral therapy . Recombination may also contribute, in principle, to overcoming the immune defenses of the host. Yet, for the adaptive advantages of genetic variation to be realized, the two viral genomes packaged in individual infecting virus particles need to have arisen from separate progenitor parental viruses of differing genetic constitution. It
17115-529: The government discovered that Mbeki was involved in military activity inside Swaziland, and he and Dhlomo – as well as Zuma, who was in the country illegally – were detained and then deported , though they managed to negotiate their deportation to the neutral territory of Mozambique rather than to South Africa. Mbeki's management of the Swaziland base later became a point of contention between him and Mac Maharaj , with whom his relationship has remained acrimonious decades later. In 1978, Maharaj and Mbeki argued at
17278-539: The government on this issue, first enacting a thousands-strong march on Parliament in February 2003, and then beginning a civil disobedience campaign in March 2003. After assurances from people within the government that a treatment plan would be forthcoming, TAC suspended its civil disobedience campaign. In the summer of 2003, TAC obtained and leaked an internally circulated government report showing that treatment would be cost-effective by reducing costly hospitalisations within
17441-462: The heads of state of Nigeria, Algeria, Mozambique, and Tanzania, perhaps his central foreign policy instrument was multilateral cooperation . Mbeki's government, and Mbeki personally, are frequently cited as the single most significant driving force behind the creation in 2001 of the New Partnership for Africa's Development (NEPAD), which aims to develop a framework for accelerating economic development and cooperation in Africa. Olivier calls Mbeki
17604-567: The home of ANC secretary general Duma Nokwe and where he intended to sit for A-level examinations. The ANC had recently been banned in the aftermath of the Sharpeville massacre , but Mbeki remained highly politically active, becoming national secretary of the African Students' Association, a new (and short-lived) youth movement envisaged as replacing the now illegal ANC Youth League. It was also during this period that Nokwe recruited Mbeki into
17767-415: The immune response to target epitopes. The RNA genome consists of at least seven structural landmarks ( LTR , TAR , RRE , PE, SLIP, CRS, and INS), and nine genes ( gag , pol , and env , tat , rev , nef , vif , vpr , vpu , and sometimes a tenth tev , which is a fusion of tat , env and rev ), encoding 19 proteins. Three of these genes, gag , pol , and env , contain information needed to make
17930-596: The initiation of relationships with many of the domestic activists who later became his political allies. Moreover, he was responsible for innovating some of the vocabulary which became emblematic of the 1980s anti-apartheid struggle, which burgeoned in the aftermath of the 1976 Soweto uprising . Such phrases as "mass democratic movement," "people's power," and the exhortation to " make the country ungovernable " are attributed to Mbeki, and gained widespread popularity inside South Africa through Radio Freedom broadcasts written by DIP or by Mbeki personally. Zuma has said that it
18093-518: The integrated DNA provirus is transcribed into RNA. The full-length genomic RNAs (gRNA) can be packaged into new viral particles in a pseudodiploid form. The selectivity in the packaging is explained by the structural properties of the dimeric conformer of the gRNA. The gRNA dimer is characterized by a tandem three-way junction within the gRNA monomer, in which the SD and AUG hairpins , responsible for splicing and translation respectively, are sequestered and
18256-504: The intolerance that comes from many who share that quality. They are loyal and true. They are their own harshest critics. They both have the gift to draw people to them... They were soul mates , different generations fusing at that particular time. — Adelaide Tambo reflects on Mbeki's relationship with O. R. Tambo , June 2002 He established some of his own high-level intelligence networks, with key underground operatives reporting directly to him, and Gevisser claims that these led to
18419-499: The left was on public display by December 2002, when Mbeki attacked what he called divisive "ultra-leftists" in a speech to the ANC's 51st National Conference . However, Mbeki clearly never subscribed to undiluted neoliberalism. He retained various social democratic programmes and principles, and generally endorsed a mixed economy in South Africa. One of the ANC's slogans in the campaign for his 2004 re-election was, "A people's contract for growth and development." He popularised
18582-630: The left wing of the ANC, and from the leaders of the ANC's Tripartite Alliance partners, the Congress of South African Trade Unions and South African Communist Party . It was these leftist elements which supported Jacob Zuma over Mbeki in the political rivalry that erupted after Mbeki removed the latter from his post as deputy president in 2005. As president, Mbeki had an apparent predilection for foreign policy and particularly for multilateralism . His Pan-Africanism and vision for an " African renaissance " are central parts of his political persona, and commentators suggest that he secured for South Africa
18745-544: The murder of HIV-positive activist Gugu Dlamini , HIV-positive and HIV-negative members of the new group began wearing the group's now-famous T-shirts with the words "HIV Positive" printed boldly in front, a strategy inspired by the apocryphal story of the Danish king wearing the yellow star marking Jews under Nazi occupation . Achmat also became famous for his pledge to not take antiretroviral medicines until all South Africans could obtain them. Quickly outgrowing its start among
18908-481: The pair developed "an unlikely rapport." Mbeki was also responsible for recruiting new MK operatives, for liaising with South African student and labour activists, and for liaising with Inkatha, which was becoming dominant in Natal. However, still another part of his duties was to act as the ANC's official representative in the country, and to maintain good diplomatic relations with the Swazi government. In March 1976,
19071-410: The patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system . In the tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce huge amounts of virus. T-tropic strains of HIV-1, or syncytia -inducing strains (SI; now called X4 viruses ) replicate in primary CD4 T cells as well as in macrophages and use
19234-430: The public-sector health system; however, the government did not endorse the report and condemned the leak. In August 2003, at its next annual congress, TAC voted to resume civil disobedience. TAC members also voted to recommend that Achmat take his medications, which he agreed he would do. At the same time, TAC began a Treatment Project to distribute medications to its activists and to other community members. Shortly after
19397-424: The ranks to head the ANC's Department of International Affairs and was involved in the ANC's negotiations with the South African government. Mbeki played a major role in turning the international media against apartheid. Raising the diplomatic profile of the ANC, Mbeki acted as a point of contact for foreign governments and international organisations and he was extremely successful in this position. Mbeki also played
19560-450: The recent death of one plaintiff in the legal case against the government on this matter. After the conclusion of the conference, TAC declared a Global Day of Action for Thursday, 24 August 2006. Protests and marches were held in the U.S., Canada, Brazil, and China by TAC supporters and sympathisers. In South Africa, police used pepper spray on protesters at the Department of Correctional Services building in central Cape Town, though no one
19723-406: The remaining 5.3% were composed of other subtypes and CRFs. Most HIV-1 research is focused on subtype B; few laboratories focus on the other subtypes. The existence of a fourth group, "P", has been hypothesised based on a virus isolated in 2009. The strain is apparently derived from gorilla SIV (SIVgor), first isolated from western lowland gorillas in 2006. HIV-2's closest relative is SIVsm,
19886-569: The request of his party, the African National Congress (ANC). Before that, he was deputy president under Nelson Mandela from 1994 to 1999. The son of Govan Mbeki , a renowned ANC intellectual, Mbeki has been involved in ANC politics since 1956, when he joined the ANC Youth League , and has been a member of the party's National Executive Committee since 1975. Born in the Transkei , he left South Africa aged twenty to attend university in England, and spent almost three decades in exile abroad, until
20049-726: The request of the ANC National Executive Committee. The ANC's decision to "recall" Mbeki was understood to be linked to a high court judgement, handed down earlier that month, in which judge Chris Nicholson had alleged improper political interference in the National Prosecuting Authority and specifically in the corruption charges against Zuma . Nicholson's judgement was overturned by the Supreme Court of Appeal in January 2009, by which time Mbeki had been replaced as president by Kgalema Motlanthe . Mbeki
20212-425: The reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes. The closely related simian immunodeficiency virus (SIV) has evolved into many strains, classified by the natural host species. SIV strains of
20375-406: The role of ambassador to the steady flow of delegates from the elite sectors of white South Africa. These included academics, clerics, business people and representatives of liberal white groups who travelled to Lusaka to assess the ANC's views on a democratic, free South Africa. Mbeki was seen as pragmatic, eloquent, rational and urbane. He was known for his diplomatic style and sophistication. In
20538-548: The rule of law and the Constitution, and the building of a people's health service. The TAC has received support from many sectors of South African society, including Supreme Court Justice Edwin Cameron , former President Nelson Mandela , Anglican Archbishop of Cape Town Njongonkulu Ndungane , Médecins Sans Frontières , and the Congress of South African Trade Unions (COSATU). In August 2006, U.S. President Barack Obama , then
20701-455: The secrecy of earlier years and openly gave interviews and access to American journalists, to the disapproval of some hardline communists. According to various sources, he was responsible for reforming the public image of the ANC from that of a terrorist organisation to that of a "government-in-waiting." When I look at Thabo, I look at my husband's son. Physically, they bear a striking resemblance... They are both perfectionists, but without
20864-516: The single-stranded viral DNA and/or interferes with reverse transcription ). The vpr protein (p14) arrests cell division at G2/M . The nef protein (p27) down-regulates CD4 (the major viral receptor), as well as the MHC class I and class II molecules. Nef also interacts with SH3 domains . The vpu protein (p16) influences the release of new virus particles from infected cells. The ends of each strand of HIV RNA contain an RNA sequence called
21027-412: The site of cell-to-cell contact, close apposition of cells, which minimizes fluid-phase diffusion of virions, and clustering of HIV entry receptors on the target cell towards the contact zone. Cell-to-cell spread is thought to be particularly important in lymphoid tissues , where CD4 T cells are densely packed and likely to interact frequently. Intravital imaging studies have supported the concept of
21190-673: The specimen is reported as repeatedly reactive and undergoes confirmatory testing with a more specific supplemental test (e.g., a polymerase chain reaction (PCR), western blot or, less commonly, an immunofluorescence assay (IFA)). Only specimens that are repeatedly reactive by ELISA and positive by IFA or PCR or reactive by western blot are considered HIV-positive and indicative of HIV infection. Specimens that are repeatedly ELISA-reactive occasionally provide an indeterminate western blot result, which may be either an incomplete antibody response to HIV in an infected person or nonspecific reactions in an uninfected person. HIV deaths in 2014 excluding
21353-553: The structural proteins Gag and Env. Gag proteins bind to copies of the virus RNA genome to package them into new virus particles. HIV-1 and HIV-2 appear to package their RNA differently. HIV-1 will bind to any appropriate RNA. HIV-2 will preferentially bind to the mRNA that was used to create the Gag protein itself. Two RNA genomes are encapsidated in each HIV-1 particle (see Structure and genome of HIV ). Upon infection and replication catalyzed by reverse transcriptase, recombination between
21516-496: The structural proteins for new virus particles. For example, env codes for a protein called gp160 that is cut in two by a cellular protease to form gp120 and gp41. The six remaining genes, tat , rev , nef , vif , vpr , and vpu (or vpx in the case of HIV-2), are regulatory genes for proteins that control the ability of HIV to infect cells, produce new copies of virus (replicate), or cause disease. The two tat proteins (p16 and p14) are transcriptional transactivators for
21679-427: The target cell surface. Gp120 binds to integrin α 4 β 7 activating LFA-1 , the central integrin involved in the establishment of virological synapses , which facilitate efficient cell-to-cell spreading of HIV-1. The gp160 spike contains binding domains for both CD4 and chemokine receptors. The first step in fusion involves the high-affinity attachment of the CD4 binding domains of gp120 to CD4. Once gp120
21842-413: The target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded enzyme, reverse transcriptase , that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded enzyme, integrase , and host co-factors . Once integrated,
22005-416: The term of former President Mbeki, and many of these deaths could have been prevented by timely implementation of access to anti-HIV drugs. Following their legal victories, and facing continuing refusal by the government to make antiretrovirals available, TAC began a campaign for universal access to AIDS treatment through the public health system. In a national congress in 2002, the group decided to confront
22168-414: The two HIV envelope glycoproteins, gp41 and gp120 . These are transported to the plasma membrane of the host cell where gp41 anchors gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. The budded virion is still immature as
22331-484: The two genomes can occur. Recombination occurs as the single-strand, positive-sense RNA genomes are reverse transcribed to form DNA. During reverse transcription, the nascent DNA can switch multiple times between the two copies of the viral RNA. This form of recombination is known as copy-choice. Recombination events may occur throughout the genome. Anywhere from two to 20 recombination events per genome may occur at each replication cycle, and these events can rapidly shuffle
22494-570: The viral DNA into the host cell's genome is carried out by another viral enzyme called integrase . The integrated viral DNA may then lie dormant, in the latent stage of HIV infection. To actively produce the virus, certain cellular transcription factors need to be present, the most important of which is NF- κ B (nuclear factor kappa B), which is upregulated when T cells become activated. This means that those cells most likely to be targeted, entered and subsequently killed by HIV are those actively fighting infection. During viral replication,
22657-536: The virus in its adaptation to avoid innate restriction factors present in host cells. Adaptation to use normal cellular machinery to enable transmission and productive infection has also aided the establishment of HIV-2 replication in humans. A survival strategy for any infectious agent is not to kill its host, but ultimately become a commensal organism. Having achieved a low pathogenicity, over time, variants that are more successful at transmission will be selected. The HIV virion enters macrophages and CD4 T cells by
22820-425: The virus is captured in the mucosa by DCs. The presence of FEZ-1 , which occurs naturally in neurons , is believed to prevent the infection of cells by HIV. HIV-1 entry, as well as entry of many other retroviruses, has long been believed to occur exclusively at the plasma membrane. More recently, however, productive infection by pH -independent, clathrin-mediated endocytosis of HIV-1 has also been reported and
22983-463: The virus may become latent , allowing the virus and its host cell to avoid detection by the immune system, for an indeterminate amount of time. The virus can remain dormant in the human body for up to ten years after primary infection; during this period the virus does not cause symptoms. Alternatively, the integrated viral DNA may be transcribed , producing new RNA genomes and viral proteins, using host cell resources, that are packaged and released from
23146-403: The virus to evade the body's immune system. The reverse transcriptase also has ribonuclease activity that degrades the viral RNA during the synthesis of cDNA, as well as DNA-dependent DNA polymerase activity that creates a sense DNA from the antisense cDNA. Together, the cDNA and its complement form a double-stranded viral DNA that is then transported into the cell nucleus . The integration of
23309-537: The virus. This virus has also lost a function of the nef gene that is present in most SIVs. For non-pathogenic SIV variants, nef suppresses T cell activation through the CD3 marker. Nef 's function in non-pathogenic forms of SIV is to downregulate expression of inflammatory cytokines , MHC-1 , and signals that affect T cell trafficking. In HIV-1 and SIVcpz, nef does not inhibit T-cell activation and it has lost this function. Without this function, T cell depletion
23472-475: The whole organism. However, a selection process leads to a predominant transmission of the R5 virus through this pathway. In patients infected with subtype B HIV-1, there is often a co-receptor switch in late-stage disease and T-tropic variants that can infect a variety of T cells through CXCR4. These variants then replicate more aggressively with heightened virulence that causes rapid T cell depletion, immune system collapse, and opportunistic infections that mark
23635-633: Was Mbeki's HIV/AIDS policy. His government did not introduce a national mother-to-child transmission prevention programme until 2002, when it was mandated by the Constitutional Court , nor did it make antiretroviral therapy available in the public healthcare system until late 2003. Subsequent studies have estimated that these delays caused hundreds of thousands of preventable deaths. Mbeki himself, like his Health Minister Manto Tshabalala-Msimang , has been described as an AIDS denialist , "dissident," or sceptic. Although he did not explicitly deny
23798-661: Was Mbeki's "drafting skills" which enabled his ascendancy in the ANC and ultimately to the presidency. In 1980, Mbeki led the ANC's delegation to Zimbabwe, where the party hoped to establish relations with Robert Mugabe 's newly elected government. This was a sensitive mission, because the ANC had historically been strongly allied to the Zimbabwe African People's Union , the arch rival of Mugabe's ZANU-PF . Working primarily through Mugabe's righthand man, future Zimbabwean president Emmerson Mnangagwa , Mbeki negotiated an extraordinarily congenial agreement between ZANU-PF and
23961-418: Was a child, his family was separated when Govan moved alone to Ladismith for a teaching job. Mbeki has said that he was "born into the struggle ," and recalls that his childhood home was decorated with portraits of Karl Marx and Mahatma Gandhi . Indeed, Govan named him after senior South African communist Thabo Mofutsanyana . Mbeki began attending school in 1948, the same year that the National Party
24124-510: Was a panelist in a plenary session co-chaired by CNN 's Sanjay Gupta entitled "Time to Deliver: The Price of Inaction". Towards the end of the session, supporters of TAC, many of whom were wearing the distinctive "HIV POSITIVE" T-shirts, took to the stage behind the panel and silently held placards containing messages such as "Fire Manto", in reference to the Health Minister , who was in attendance. TAC members and supporters also took over
24287-423: Was already seen as his most likely successor. In December 1997, the ANC's 50th National Conference elected Mbeki unopposed to succeed Mandela as ANC president. On some accounts, the election was not contested because the top leadership had prepared assiduously for the conference, lobbying and negotiating on Mbeki's behalf in the interest of unity and continuity. Pursuant to the 1999 national elections , which
24450-433: Was appointed head of the ANC's information department in 1984 and then became head of the international department in 1989, reporting directly to Oliver Tambo , then President of the ANC. Tambo was Mbeki's long-time mentor. In 1985, Mbeki was a member of a delegation that began meeting secretly with representatives of the South African business community, and in 1989, he led the ANC delegation that conducted secret talks with
24613-592: Was appointed national deputy president. In subsequent years, it became apparent that he was Mandela's chosen successor, and he was elected unopposed as ANC president in 1997, enabling his rise to the presidency as the ANC's candidate in the 1999 elections . While deputy president, Mbeki had been regarded as a steward of the government's Growth, Employment and Redistribution policy, introduced in 1996, and as president he continued to subscribe to relatively conservative, market-friendly macroeconomic policies. During his presidency, South Africa experienced falling public debt ,
24776-535: Was born on 18 June 1942 in Mbewuleni , a small village in the former homeland of Transkei , now part of the Eastern Cape . The second of four siblings, he had one sister, Linda (born 1941, died 2003), and two brothers, Moeletsi (born 1945) and Jama (born 1948, died 1982). His parents were Epainette (died 2014), a trained teacher, and Govan (died 2001), a shopkeeper, teacher, journalist, and senior activist in
24939-592: Was elected onto the ANC's top decision-making organ, the National Executive Committee . It was during this period that he began to ghostwrite some of Tambo's speeches and reports, and he accompanied Tambo on important occasions, such as to the infamous December 1972 meeting with Mangosuthu Buthelezi , the head of Inkatha , in London. In 1973, he helped to establish the ANC's office in Botswana, considered
25102-475: Was elected with a mandate to legislate apartheid . The Bantu Education Act was implemented towards the end of his school career, and in 1955 he arrived at the Lovedale Institute , an eminent mission school outside Alice , as part of the last class which would be permitted to follow the same curriculum as white students. At Lovedale, he was a year behind Chris Hani , his future colleague and rival in
25265-727: Was expanded and consolidated under his administration, was criticised precisely for benefitting only a small black elite and thereby failing to address inequality . According to academic and diplomat Gerrit Olivier , during his presidency Mbeki "succeeded in placing Africa high on the global agenda." He was known for his Pan-Africanism , having emphasised related themes both in his famous " I am an African " speech in 1996 and in his first speech to Parliament as president in June 1999, when he foregrounded his trademark ideal of an " African renaissance ." He advocated for greater solidarity among African countries and, in place of reliance on Western intervention and aid, for greater self-sufficiency for
25428-405: Was firmly opposed to forcible or manufactured regime change in Zimbabwe, and also opposed the use of sanctions. The Economist posited an "Mbeki doctrine" holding that South Africa "cannot impose its will on others, but it can help to deal with instability in African countries by offering its resources and its leadership to bring rival groups together, and to keep things calm until an election
25591-434: Was launched on 10 December 1998, International Human Rights Day . Zackie Achmat , whom The New Yorker calls "the most important dissident in the country since Nelson Mandela", joined with a group of ten other activists to found the group after anti-apartheid gay rights activist Simon Nkoli died from AIDS even as highly active antiretroviral therapy was available to wealthy South Africans. Shortly thereafter, prompted by
25754-411: Was not elected to any of the "Top Six" leadership positions. Sisulu was elected ANC deputy president, almost certainly as a compromise candidate, and trade unionist Cyril Ramaphosa was elected secretary general. According to historian Tom Lodge, Ramaphosa's election was a putsch carried out by the party's "internal wing," in defiance of the former exiles and political prisoners who had hitherto dominated
25917-429: Was promoted again: he replaced Nokwe as head of DIP, and simultaneously was appointed Tambo's political secretary, an extremely influential position in which he became one of Tambo's closest advisors and confidantes. He also continued to ghostwrite for Tambo, now in a formal capacity. At DIP, his approach was encapsulated by the change he made to the department's name, replacing "propaganda" with "publicity." He eschewed
26080-448: Was recently suggested to constitute the only route of productive entry. Shortly after the viral capsid enters the cell, an enzyme called reverse transcriptase liberates the positive-sense single-stranded RNA genome from the attached viral proteins and copies it into a complementary DNA (cDNA) molecule. The process of reverse transcription is extremely error-prone, and the resulting mutations may cause drug resistance or allow
26243-556: Was sent to Lusaka , Zambia, where the ANC-in-exile had set up its new headquarters under acting president Tambo. He was to fill the post of administrative secretary to the ANC Revolutionary Council , a body newly established to coordinate the political and military efforts of the ANC and SACP. He was later moved to the propaganda section, but continued to attend the council's meetings, and in 1975 he (again alongside Hani)
26406-500: Was seriously hurt. Similar protests in Gauteng , Eastern Cape , Limpopo , and KwaZulu-Natal were not met with violence. Over 2000 people took part in the demonstrations. The TAC's objective was to deliver its five demands, which include the convening of a national meeting and plan for the HIV/AIDS crisis, the dismissal of the Health Minister, the immediate treatment of prisoners, respect for
26569-489: Was to be – as in Swaziland – the ANC's first representative to the country. Although there was some debate about whether the appointment was a signal that he had been sidelined, Gevisser says that Mbeki performed well in Lagos, establishing good relations with Olusegun Obasanjo 's regime and establishing an ANC presence to eclipse that of its rival Pan Africanist Congress (PAC). When he returned to Lusaka from Lagos in 1978, he
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