|Genetic Variability: Implications for the Development of HIV Vaccines (UNAIDS, 1996, 16 p.)|
HIV-1 genetic subtypes are unevenly distributed in different geographical locations [8-13,21-24]. Subtype B viruses are more prevalent in North America, Latin America and the Caribbean, Europe, Japan and Australia. Almost every subtype is present in sub-Saharan Africa, with subtypes A and D predominating in central and eastern Africa, and subtype C in southern Africa. Subtype C is also prevalent in India and it has been recently identified in southern Brazil . Subtype E was initially identified in Thailand, and is also present in the Central African Republic [10,13,22-24]. Subtype F was initially described in Brazil and in Romania . The most recent subtypes described are G, found in Russia and Gabon, and subtype H, found in Zaire and in Cameroon [15,16]. As mentioned before, group O viruses have been identified in Cameroon and also in Gabon [17,18].
However, the above information on the geographical distribution of HIV-1 genetic subtypes is mostly based on limited data which has been generated from small descriptive studies. Well-designed molecular epidemiology studies are thus needed to obtain statistically significant information on the distribution of HIV-1 subtypes in different parts of the world, and to establish possible correlations between genetic subtypes and biological and/or epidemiological characteristics, including mode of transmission and possible segregation of specific HIV-1 subtypes in particular populations with different risks for HIV-1 infection . Studies are also required to better understand the dynamics and driving forces of the epidemic, including cumulative prevalence, as well as incidence of infection with different subtypes. This may allow tracking the spread of the epidemic between different populations, countries, and continents. Such information will be required for the appropriate design of efficacy trials of HIV candidate vaccines, and may be essential for planning strategies for the utilization of future HIV/AIDS vaccines.
The practical implementation of these molecular epidemiology studies is being greatly facilitated by the development of two simple techniques for HIV-1 subtyping, the heteroduplex mobility assay (HMA) and V3-peptide ELISA. Since HMA relies on the amplification of proviral DNA, an important limitation of the technique has been the need to obtain peripheral blood mononuclear cells from infected individuals [20,21,30]. However, HMA is now being modified by the introduction of a reverse transcription step, which will allow the use of small amounts of serum or plasma as a source of viral sequences . The other technique for HIV subtype determination is based on ELISA reactivity of patient's serum with peptides derived from different V3 loop sequences. This is a very practical approach for large-scale screening and is particularly useful in locations where only a few well characterized subtypes are known to be present. Considerable serological cross-reactivity has been observed between A and C subtypes, suggesting that these two genetic variants may fall within a single serotype. Cross-reactivity has also been observed between subtype B and subtype D sera, although to a lesser extent. The genetic variation observed in the V3 region of subtype B viruses from different geographical locations (e.g., North America/Europe, Brazil and Thailand) is also reflected in the reactivity in V3 peptide serology, and may identify these viruses as distinct serotypes [32,33]. Different algorithms for HIV subtype determination, combining initial screening by peptide-ELISA followed by HMA, are presently being developed [24,34].