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),[1][2] a condition in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive.[3] Without treatment, average survival time after infection with HIV is estimated to be 9 to 11 years, depending on the HIV subtype.[4] 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.[5][6] 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. [7][8][9][10] 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. [11] HIV infection leads to low levels of CD4+ T cells through a number of mechanisms, including pyroptosis of abortively infected T cells,[12] apoptosis of uninfected bystander cells,[13] direct viral killing of infected cells, and killing of infected CD4+ T cells by CD8+ cytotoxic lymphocytes that recognize infected cells.[14] 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 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).[16] A total of 39 ORFs are found in all six possible reading frames (RFs) of HIV-1 complete genome sequence,[17] 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).[18] 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.[19]
  • Subtype B is the dominant form in Europe, the Americas, Japan, and Australia.[20] In addition, subtype B is the most common form in the Middle East and North Africa.[21] It may have been exported from Africa when Haitian professionals visited Kinshasa in the 1960s and brought it to Haiti in 1964.[18]
  • Subtype C is the dominant form in Southern Africa, Eastern Africa, India, Nepal, and parts of China.[20]
  • Subtype D is generally only seen in Eastern and central Africa.[20]
  • 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.[22]
  • Subtype G (and the CRF02_AG) have been found in Africa and central Europe.[22]
  • Subtype H is limited to central Africa.[22]
  • 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[23]
  • Subtype K is limited to the Democratic Republic of Congo (DRC) and Cameroon.[22]
  • Subtype L is limited to the Democratic Republic of Congo (DRC). [24]

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.[28] As of 2015, less than 20 Group N infections have been recorded.[29]

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.[15] It is reportedly most common in Cameroon, where a 1997 survey found that about 2% of HIV-positive samples were from Group O.[30] 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.[31]

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”.[32][33][34]


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[35]. The first case in the United States was in 1987.[36] Many test kits for HIV-1 will also detect HIV-2.[37]

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.[38][39] 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.).[40]

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. [38]

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.[38][39]

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