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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), a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive. Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype. In most cases, HIV is a sexually transmitted infection and occurs by contact with or transfer of blood, pre-ejaculate, semen, and vaginal fluids. Research has shown (for both same-sex and opposite-sex couples) that HIV is untransmittable through condomless sexual intercourse if the HIV-positive partner has a consistently undetectable viral load. Non-sexual transmission can occur from an infected mother to her infant during pregnancy, during childbirth by exposure to her blood or vaginal fluid, and through breast milk.  Within these bodily fluids, HIV is present as both free virus particles and virus within infected immune cells. HIV infects vital cells in the human immune system, such as helper T cells (specifically CD4+ T cells), macrophages, and dendritic cells.  HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells, apoptosis of uninfected bystander cells, direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells. When CD4+ T cell numbers decline below a critical level, cell-mediated immunity is lost, and the body becomes progressively more susceptible to opportunistic infections, leading to the development of AIDS. HIV-1 HIV-1 is the most common and pathogenic strain of the virus. Scientists divide HIV-1 into a major group (Group M) and two or more minor groups, namely Group N, O and possibly a group P. Each group is believed to represent an independent transmission of SIV into humans (but subtypes within a group are not). A total of 39 ORFs are found in all six possible reading frames (RFs) of HIV-1 complete genome sequence, but only a few of them are functional. Group M With ‘M’ for “major”, this is by far the most common type of HIV, with more than 90% of HIV/AIDS cases deriving from infection with HIV-1 group M. This major HIV virus which was the source of pre-1960 pandemic viruses originated in the 1920s in Léopoldville, the Belgian Congo, today known as Kinshasa, which is now the capital of the Democratic Republic of Congo (DRC). The M group is subdivided further into clades, called subtypes, that are also given a letter. There are also “circulating recombinant forms” or CRFs derived from recombination (https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mmed&part=A2330) between viruses of different subtypes which are each given a number. CRF12_BF, for example, is a recombination between subtypes B and F. • Subtype A is common in eastern Africa. • Subtype B is the dominant form in Europe, the Americas, Japan, and Australia. In addition, subtype B is the most common form in the Middle East and North Africa. It may have been exported from Africa when Haitian professionals visited Kinshasa in the 1960s and brought it to Haiti in 1964. • Subtype C is the dominant form in Southern Africa, Eastern Africa, India, Nepal, and parts of China. • Subtype D is generally only seen in Eastern and central Africa. • Subtype E is found in Southeast Asia which is the dominant form for heterosexuals as transmission rate is much higher than most other subtypes. • Subtype F has been found in central Africa, South America, and Eastern Europe. • Subtype G (and the CRF02_AG) have been found in Africa and central Europe. • Subtype H is limited to central Africa. • Subtype I was originally used to describe a strain that is now accounted for as CRF04_cpx, with the cpx for a “complex” recombination of several subtypes. • Subtype J is primarily found in North, Central and West Africa, and the Caribbean.  • Subtype K is limited to the Democratic Republic of Congo (DRC) and Cameroon. • Subtype L is limited to the Democratic Republic of Congo (DRC).  Group N HIV-1 subtype prevalence in 2002 The ‘N’ stands for “non-M, non-O”. This group was discovered by a Franco-Cameroonia team in 1998, when they identified and isolated the HIV-1 variant strain, YBF380, from a Cameroonian woman who died of AIDS in 1995. When tested, the YBF380 variant reacted with an envelope antigen from SIVcpz rather than with those of Group M or Group O, indicating it was indeed a novel strain of HIV-1. As of 2015, less than 20 Group N infections have been recorded. Group O The O (“Outlier”) group has infected about 100,000 individuals located in West-Central Africa and is not usually seen outside of that area. It is reportedly most common in Cameroon, where a 1997 survey found that about 2% of HIV-positive samples were from Group O. The group caused some concern because it could not be detected by early versions of the HIV-1 test kits. More advanced HIV tests have now been developed to detect both Group O and Group N. Group P In 2009, a newly analyzed HIV sequence was reported to have greater similarity to a simian immunodeficiency virus recently discovered in wild gorillas (SIVgor) than to SIVs from chimpanzees (SIVcpz). The virus had been isolated from a Cameroonian woman residing in France who was diagnosed with HIV-1 infection in 2004. The scientists reporting this sequence placed it in a proposed Group P “pending the identification of further human cases”. HIV-2 HIV-2 has not been widely recognized outside of Africa. The first identification of HIV-2 occurred in Senegal by microbiologist Souleymane Mboup and his collaborators . The first case in the United States was in 1987. Many test kits for HIV-1 will also detect HIV-2. As of 2010, there are 8 known HIV-2 groups (A to H). Of these, only groups A and B are pandemic. Group A is found mainly in West Africa, but has also spread globally to Angola, Mozambique, Brazil, India, Europe, and the US. Despite the presence of HIV-2 globally, Group B is mainly confined to West Africa. Despite its relative confinement, HIV-2 should be considered in all patients exhibiting symptoms of HIV that not only come from West Africa, but also anyone who has had any body fluid transfer with a person from West Africa (i.e. needle sharing, sexual contact, etc.). HIV-2 is closely related to simian immunodeficiency virus endemic in sooty mangabeys (Cercocebus atys atys) (SIVsmm), a monkey species inhabiting the forests of Littoral West Africa. Phylogenetic analyses show that the virus most closely related to the two strains of HIV-2 which spread considerably in humans (HIV-2 groups A and B) is the SIVsmm found in the sooty manga beys of the Tai forest, in western Ivory Coast.  There are six additional known HIV-2 groups, each having been found in just one person. They all seem to derive from independent transmissions from sooty manga beys to humans. Groups C and D have been found in two people from Liberia, groups E and F have been discovered in two people from Sierra Leone, and groups G and H have been detected in two people from the Ivory Coast. Each of these HIV-2 strains, for which humans are probably dead-end hosts, is most closely related to SIVsmm strains from sooty manga beys living in the same country where the human infection was found.