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= Evolution of HIV =

Evolutionary Origin of HIV
Human immunodeficiency virus is a retrovirus that causes HIV infection which over time progresses into acquired immunodeficiency syndrome (AIDS). HIV can be classified into two major subgroups: HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is closely related to the simian immunodeficiency virus (SIV) virus found in chimpanzees as well as gorillas, while HIV-2 is closely related to the SIV virus found in the sooty mangabey African primate. In 1999, researchers identified a strain of simian immunodeficiency that was almost identical to the HIV that had infected human hosts. This discovery confirmed the belief that HIV-1 arose from the virus crossing over from chimps to humans and the consequent viral adaptation to the human body as a host. Following this discovery, a subsequent study found that the Chimpanzee strain of the virus was acquired from monkeys, presumably because of hunting of the monkeys by chimpanzees.

HIV-1 viruses have been found to be more virulent and transmissible in humans than HIV-2. Both of the subtype viruses the result of a crossover transmission from simian species. The widely accepted “hunter” theory proposes that the transfer of the virus from chimpanzees to humans occurred when human hunters killed infected chimpanzees. The blood from the killed chimpanzees likely contained the SIV and the virus was likely able to infect the humans via cuts or sores on the person preparing the chimpanzee for consumption. The virus then likely evolved to become adapted to the human host and became HIV-1. While there are other plausible transfer mechanisms, the hunter hypothesis remains consistent with available information and has not been strongly challenged.

HIV-2 likely followed a similar pattern as that of the chimpanzees in which sooty mangabey monkeys were killed and consumed which resulted in the infection of humans. The virus likely then evolved to become adapted to the human host in a similar manner to the HIV-1 virus.

While the HIV-1 virus entered the human population several times, only one of these has resulted in a global pandemic: the HIV-1 group M virus that originated from the SIV chimpanzee in southeastern Cameroon which is the preliminary cause of the AIDS pandemic. Group M consists of 9 subtypes (A-K). HIV-2 in comparison makes up only about 3% of cases worldwide and is mainly found in West Africa. The viral diversity due to multiple origins and extensive evolution of HIV is one of the factors that makes it difficult to develop an effective vaccine to target HIV.

I likely will include a link to the “Subtypes of HIV” page for people to reference for this section as some of the content on the this page and that page is similar.

Diversification of HIV
HIV-1 is the viral strain responsible for the global pandemic, accounting for about 95% of infections worldwide. HIV-2 on the other hand has remained situated and concentrated in West Africa and has rarely been seen in other countries. The strains of HIV-1 can be classified further into various groups and strains. Firstly, there is the HIV-1 group M virus which is predominantly responsible for the AIDS pandemic. The group M HIV strain is highly diverse as it is thought to have been evolving in humans since the 1920s..

Within group M, there are further distinct subcategories (A, B, C, D, F, G, H, J, and K) that are characterized by genetic traits. In the Americas, Europe, and Australia, the dominant subtype within group M is B, however, it only represents about 12% of the global infections. The most common HIV strain worldwide is the C strain of HIV-1 group M. Currently, there is little research done on any strains other than B, however, the antiretroviral drugs that treat the B strain generally work on most other strains.

In addition to group M, there is also the group N which encompasses a small group of people in Cameroon. This group has very few cases; since 2015, there have been fewer than 20 group N infections.

Furthermore, there is Group O which has similar variability to group M, but similar to group N, it is very rare outside of West Africa. Group P is the newest group of HIV-1 and is similarly confined in Cameroon, but has lineated significantly from groups M, N, and O.

Though HIV has various strains and groups, the virus is capable of undergoing mutations within an individual body and developing into another HIV strain. Due to the vast number of strains that HIV can lineate into, therapy of HIV is complicated. Its ability to evolve into various strains and acquire drug resistant mutations makes its diversification important to consider in studying the evolution of HIV.

Refer to Subtypes of HIV

Evolution of HIV in Therapy
Initially, single drug therapies were administered to patients in the 1990s to patients infected with HIV in order to prevent AIDS. Though briefly effective, HIV acquired resistance rendering single drug treatment options ineffective. Next, the use of combination therapy was developed in the late 1990s. In 1996, a cocktail therapy known as Highly Active Antiretroviral Therapy (HAART) was developed, consisting most commonly of protease inhibitors, which inhibit viral replication, and two types of reverse transcriptase inhibitors that inhibit the process of reverse transcription.

This new combination therapy delays the onset and progression of HIV to AIDS through reduction of the viral load via suppression of integration, transcription, and replication. HAART combats HIV at different stages in its replication and integration cycle through the combination of multiple drugs that target these stages. For the HIV virus to acquire resistance to this combination therapy, numerous mutations in the same genome are needed to confer resistance to the multiple drugs administered in HAART. Though combination therapy does reduce the likelihood of HIV drug resistance, virologic failure does take place in which HIV acquires the necessary mutations for resistance.

Virologic failure takes place when HIV undergoes specific mutations that give it resistance to the nucleoside and nonnucleoside reverse transcriptase inhibitor drugs and the protease inhibitor drugs. Current research work is analyzing the mechanisms by which HIV acquires resistance mutations in response to antiretroviral therapy in order to clarify the role HIV evolution plays in therapy. The development of antiviral drug resistance poses a major threat to effective treatment against HIV-1. Given that drug treatment failure is associated with the extensive accumulation of drug resistance mutations, studying this mutation pattern can highlight the mechanisms by which evolution of HIV alters therapeutics.