HIV types, groups and subtypes

HIV types, groups and subtypes.
HIV is a highly variable virus which mutates very readily. This means there are many different strains of HIV, even within the body of a single infected person.

Based on genetic similarities, the numerous virus strains may be classified into types, groups and subtypes.

What is the difference between HIV-1 and HIV-2? There are two types of HIV: HIV-1 and HIV-2. Both types are transmitted by sexual contact, through blood, and from mother to child, and they appear to cause clinically indistinguishable AIDS. However, it seems that HIV-2 is less easily transmitted, and the period between initial infection and illness is longer in the case of HIV-2.

Worldwide, the predominant virus is HIV-1, and generally when people refer to HIV without specifying the type of virus they will be referring to HIV-1. The relatively uncommon HIV-2 type is concentrated in West Africa and is rarely found elsewhere.

How many subtypes of HIV-1 are there?
The strains of HIV-1 can be classified into three groups : the "major" group M, the "outlier" group O and the "new" group N. These three groups may represent three separate introductions of simian immunodeficiency virus into humans.

Group O appears to be restricted to west-central Africa and group N - discovered in 1998 in Cameroon - is extremely rare. More than 90% of HIV-1 infections belong to HIV-1 group M and, unless specified, the rest of this page will relate to HIV-1 group M only.

Within group M there are known to be at least nine genetically distinct subtypes (or clades) of HIV-1. These are subtypes A, B, C, D, F, G, H, J and K.

Occasionally, two viruses of different subtypes can meet in the cell of an infected person and mix together their genetic material to create a new hybrid virus (a process similar to sexual reproduction).1 Many of these new strains do not survive for long, but those which infect more than one person are known as "circulating recombinant forms" or CRFs. For example, the CRF A/B is a mixture of subtypes A and B.

The classification of HIV strains into subtypes and CRFs is a complex issue and the definitions are subject to change as new discoveries are made. Some scientists talk about subtypes A1, A2, A3, F1 and F2 instead of A and F, though others regard the former as sub-subtypes.

What about subtypes E and I?
One of the CRFs is called A/E because it is thought to have resulted from hybridization between subtype A and some other "parent" subtype E. However, no-one has ever found a pure form of subtype E. Confusingly, many people still refer to the CRF A/E as "subtype E" (in fact it is most correctly called CRF01_AE).

A virus isolated in Cyprus was originally placed in a new subtype I, before being reclassified as a recombinant form A/G/I. It is now thought that this virus represents an even more complex CRF comprised of subtypes A, G, H, K and unclassified regions. The designation "I" is no longer used.2,3

Where are the different subtypes and CRFs found?
The HIV-1 subtypes and CRFs are very unevenly distributed throughout the world, with the most widespread being subtypes B and C.

Subtype C is largely predominant in southern and eastern Africa, India and Nepal. It has caused the world's worst HIV epidemics and is responsible for around half of all infections.

Historically, subtype B has been the most common subtype/CRF in Europe, the Americas, Japan and Australia. Although this remains the case, other subtypes are becoming more frequent and now account for at least 25% of new infections in Europe.

Subtype A and CRF A/G predominate in west and central Africa, with subtype A possibly also causing much of the Russian epidemic4 . Subtype D is generally limited to east and central Africa; A/E is prevalent in south-east Asia, but originated in central Africa; F has been found in central Africa, south America and eastern Europe; G and A/G have been observed in western and eastern Africa and central Europe.

Subtype H has only been found in central Africa; J only in central America; and K only in the Democratic Republic of Congo and Cameroon.

Are more subtypes likely to "appear"?
It is almost certain that new HIV genetic subtypes and CRFs will be discovered in the future, and indeed that new ones will develop as virus recombination and mutation continue to occur. The current subtypes and CRFs will also continue to spread to new areas as the global epidemic continues.

The implications of variability
Are there differences in transmission?
It has been observed that certain subtypes/CRFs are predominantly associated with specific modes of transmission. In particular, subtype B is spread mostly by homosexual contact and intravenous drug use (essentially via blood), while subtype C and CRF A/E tend to fuel heterosexual epidemics (via a mucosal route).

Whether there are biological causes for the observed differences in transmission routes remains the subject of debate. Some scientists, such as Dr Max Essex of Harvard, believe such causes do exist. Among their claims are that subtype C and CRF A/E are transmitted much more efficiently during heterosexual sex than subtype B.5,6 However, this theory has not been conclusively proven.7,8

More recent studies have looked for variation between subtypes in rates of mother-to-child transmission. It has been claimed that such transmission is more common with subtype D than subtype A9, and that subtype C is more often transmitted than either D or A10 .