HIV Subtypes: a quick primer

Background

Advances in genetic technology in the 1980s made it possible to duplicate in the test tube by a technique called polymerase chain reaction (PCR) the RNA or DNA forms of the genetic "code" of HIV. This revolutionary application made it possible to use the genetic information to distinguish the two major types of HIV, type1(HIV-1) and type 2 (HIV-2), as well as different strains within each type.
HIV-1 is more virulent than HIV-2 and is the predominant strain around the world. To date, HIV-2 is found principally in West Africa, and constitutes a small minority of infections in other parts of Africa, South America and West India.

Applications

As with other typable infectious diseases, the ability to compare and distinguish specific HIV virus isolates from individuals makes it possible to track the spread of virus from person to person, country to country and region to region.
Surveillance and knowledge about the geographic extent of HIV-1 strains is important to confirm or rule out chains of transmission between individuals and to provide clues as to how the epidemic is spreading. Furthermore, the development and performance of AIDS vaccines and clinical prognosis may be affected by biological differences in the manifestations of infection with different subtypes.

HIV-1 and HIV-2 Subtypes

To date, two major groups of HIV-1 exist, "M" and "O" (for outlier). The virus that causes the great majority of HIV-1 infections diagnosed and studied in the world are in the M group. The O group includes a small number of isolates discovered in Africa (with one case found recently in the U.S.). These are genetically quite distant from the M group, and consequently may not show up on some standard laboratory tests for HIV-1.
HIV-2 is divided in the subtypes A and B, but further subtypes C through E have recently been characterized by DNA sequencing.

Geographic Distribution

In the predominant M group of HIV-1, 8 subtypes A through H have been identified to date. Most all are found in one area or another of Africa, while in other regions of the world, certain subtypes predominate.
In Europe, subtype B is predominant in men who have sex with men, while a variety of subtypes are found in the relatively small numbers of people infected through heterosexual contact in Europe and the countries of the former Soviet Union. Subtype B has also been noted in Indonesia, the Philippines and Taiwan.
In India, subtype C predominates, with a small number of A and B infections. In Thailand, E predominates, while a minority of B infections occur in drug users, and this B strain has also been found in drug users in Myanmar (Burma), Malaysia and southeast China.
In the Americas (North, South and Central), as well as in Australia, New Zealand and Japan, subtype B is most common. Subtype F occurs in Romania, and along with subtype C also is found in a small proportion of strains in Brazil.

Biological Implications

Preliminary epidemiological work in Thailand suggests that subtype E may be more transmissible by the sexual route than subtype B, while preliminary clinical studies there suggested that subtype E infection may produce significantly lower levels of CD4+ T-cells than does infection with subtype B. Preliminary in vitro work in the U.S. suggests that subtypes C and E may more readily infect the Langerhans cells that line the sexual tract than subtype B.
It is not known whether an AIDS vaccine designed against one subtype of HIV-1 will work to protect the vaccine recipient against other subtypes to which they may be exposed. Knowledge of which subtypes exist in which proportions in specific geographic areas will be important for designing AIDS vaccine trials and determining which antigens might need to be included in future vaccines. Simple economical techniques have been developed for collecting HIV-1 in non-infectious dried blood spots that can be mailed safely without refrigeration to laboratories capable of performing PCR and subtyping.

Research Needs and Implications

Some countries have multiple subtypes circulating in substantial numbers, such as E and B in Thailand, A and D in Uganda, and B and C in South Africa. Prospective studies among infected persons who continue to expose themselves to HIV (e.g., sex workers and injecting drug users) would be useful to determine whether infection with one subtype provides protection against "superinfection" with another subtype. Recent data from Senegal suggest that HIV-2 infection provides partial protection from HIV-1 superinfection. If superinfection does not occur as frequently as might be expected, this would bode well for the possibility that killed, whole-virus or live, attenuated vaccines might work if they can mimic the natural immune response to HIV.