The present study characterized new CRF02_AG strains sampled from Cameroonian subjects, as well as strains from both Italian and African individuals residing in Italy. First, the molecular epidemiology of this subtype in West-Central African countries was investigated, with particular focus on Cameroon, an epicenter of the African epidemic. The phylogenetic analysis showed a continuous exchange of viral strains between Cameroon and other African countries, as well as the presence of three different monophyletic clades within Cameroon, all of which originated around the mid-1970s. All clades were related to strains from different West African countries, none of which, however, is geographically adjacent to Cameroon. A potential explanation is that the French occupation of Burkina Faso, Ivory Coast, and Cameroon until the 1960s led to a founder effect in Cameroon, arising from connections among countries within the French sphere of influence.
The lack of metapopulation structure within the Cameroonian epidemic, in which none of the three major clades was significantly associated with a specific geographic area, is consistent with GIS data. Accessibility maps indicated that Southern Cameroon is characterized by developed road networks and harbor areas that may have significantly fostered HIV-1 spread after initially limited introduction from other African countries. This is in agreement with the hypothesis, recently suggested by Gray et al.
that accessibility plays a major role in the emergence and spread of viral regional epidemics. This hypothesis is also supported by data showing that the most vulnerable groups in Cameroon include truck drivers, mobile populations, and military personnel.50
The phylogenetic analysis also showed that CFR02_AG strains from Italian individuals, as well as from non-Cameroonian African immigrants residing in a small locale of northern Italy, were intermixed throughout the tree. In particular, most of the Italian sequences were only distantly related in the phylogeny, which was indicative of at least four independent events leading to infection of Italian subjects. Additional studies including sequences from multiple regions in Italy are needed to assess the frequency and extent of CRF02_AG spillover into the country. However, given that the HIV strains analyzed were sampled from a relatively small geographic area, it is remarkable that several independent introductions were already observed.
Data from the Italian National Institute of Statistics showed that in recent years African immigrants have constantly been increasing in the country (). In particular, from 2002 to 2008 the number of Cameroonians residing in Italy has almost tripled, from 2926 (8% of immigrants living in Italy) in 2002 to 7994 (21% of immigrants living in Italy) in 2008. A similar trend could be observed for immigrants from other African countries with a significant AG epidemic both bordering and not bordering Cameroon. Taken together these findings suggest that conditions may be present for the development of a generalized epidemic of this recombinant form in Italy that might significantly impact HIV-1 molecular epidemiology thus far predominantly characterized by subtype B infections.
FIG. 5. Citizens from Cameroon and other African countries (bordering and not bordering Cameroon) involved in the spread of CRF02_AG and residing in Italy: demographic balance over the years 2002–2008. For each year, the demographic balance is updated (more ...)
In the past years the migration trends from Africa to Western Europe have been changing the face of the AIDS epidemic in terms of subtype distribution/prevalence. Italy's position in the Mediterranean Sea makes it a strategic migration route. Therefore, understanding the CRF02_AG epidemic from Africa to Italy may also play a fundamental role in assessing the potential spread of this viral strain within Europe and North America, especially given the enormous exchange of persons and goods between the two continents.
Understanding HIV molecular epidemiology and the potential future spread of different non-B subtypes also has clinical relevance. It is already known that differences among HIV-1 genetic forms may impact clinical management and surveillance of drug resistance, particularly as treatment is expanded to HIV-1 non-B strains.51–55
Moreover, HIV-1 subtypes are relevant for vaccine design. Although cross-clade immune reactivity has been detected among individuals and vaccine recipients, it is reasonable to expect that a vaccine with an antigenic composition including CRFs may induce a more effective response.56