Certain subtypes are known for their increased virulence or drug resistance to different medications used to treat HIV.

One of the prevailing challenges in the pursuit of effective management of HIV is the virus's pronounced genetic variability and rapid viral evolution.

[19] This group was discovered by a Franco-Cameroonian team in 1998, when they identified and isolated the HIV-1 variant strain, YBF380, from a Cameroonian woman who died of AIDS in 1995.

[29] The first confirmed case of HIV-2 was a Portuguese man who was treated at the London Hospital for Tropical Diseases and later died in 1987.

Group A is found mainly in West Africa, but has also spread to Angola, Mozambique, Brazil, India, Europe, and the US.

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 mangabeys of the Tai forest, in western Ivory Coast.

[32][33] HIV-2 diagnosis can be made when a patient has no symptoms but positive blood work indicating the individual has HIV.

While the mechanisms are not clearly understood for HIV-1 and HIV-2, it is known that they use different pathways and patterns, making the algorithms used to evaluate HIV-1 resistance-associated mutations irrelevant to HIV-2.

[37] A study found that individuals who contract HIV-2 before HIV-1 tend to have a slower rate of disease progression, suggesting that the immune response to HIV-2 may limit the proliferation of HIV-1.

If HIV-2 is present, a number of perinatal ART drugs may be given as a prophylactic to lower the risk of mother-to-child transmission.

During the early stages of mutation, evolution appears to be neutral due to the absence of an evolutionary response.

However, when examining the virus in several different individuals, convergent mutations can be found appearing in these viral populations independently.

[39] HIV evolution within a host influences factors including the virus' set-point viral load.

[40] One includes the continuous battle to evolve and overcome the immune system which slows down the evolution of HIV and shifts the virus’ focus towards a population level.

The last mechanism focuses on the virus' preference to transmit founding viral strains stored during the early stages of infection.

[40] HIV is evolving toward a milder form, but it is still "an awfully long way" from no longer being deadly,[41][42] with severe variants still appearing.

[43][44] Isolates of HIV-1 and HIV-2 with resistance to antiretroviral drugs arise through natural selection and genetic mutations, which have been tracked and analyzed.

The Stanford HIV Drug Resistance Database and the International AIDS Society publish lists of the most important of these; first year listing 80 common mutations, and the latest year 93 common mutations, and made available through the Stanford HIV RT and Protease Sequence Database.