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COMPARATIVE PHYLODYNAMICS OF HIV-1 SUBTYPE B, SUBTYPE C AND CRF02_AG EPIDEMICS ACROSS DIFFERENT GEOGRAPHICAL REGIONS
Silva, Daiana Mir da | Date Issued: 2018
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.
The emergence and reemergence of infectious diseases and the persistent circulation of human pathogens, have stimulated a growing interest and effort to understand the origins and causes of disease outbreaks and dissemination. The field of phylodynamics, has proven to be a proper framework for the integration of epidemiological and evolutionary dynamics, and a key source of information about the spatiotemporal patterns of epidemics and their way of transmission through a susceptible population. This thesis aimed to characterize the demographic dynamics exhibited by some clades of HIV-1 across multiple epidemiological scales in different geographical regions by applying a phylodynamic approach. The specific HIV-1 strains analyzed were: the subtype B, the CRF02_AG and the subtype C. Despite that subtype B is the most widely spread HIV-1 variant in Latin America, the precise number, geographic extension and dissemination dynamics of major subtype B pandemic clades circulating in the region was largely unknown. Among the 90 circulating recombinant forms (CRFs) currently described, CRF02_AG is responsible for the largest number of global infections and the most prevalent HIV variant in West and West-Central Africa. Little was known, however, about the number and demographic patterns of major CRF02_AG lineages in those African regions In addition to being the most prevalent lineage globally, the HIV-1 subtype C accounts for an important fraction of HIV infections in East Africa and South Brazil, but its evolutionary dynamics in those regions had not been fully analyzed. The main results obtained show that one third of HIV-1 subtype B infections in Latin America originated from the spread of a few B pandemic founder strains probably introduced in the region since the late 1960s onwards. Our analyses also revealed that major West and West-Central African CRF02_AG clades are the result of a few founder strains introduced from Central Africa between late 1960s and mid-1980s. The West African CRF02_AG clade showed a high geographic dissemination and its introduction in Asia and Europe lead to the emergence of local epidemics. The coalescent and the birth-death phylodynamic approaches applied for the analyses of the subtype C lineages circulating in Eastern Africa and Southern Brazil pointed to an initial stage of exponential growth in all them until roughly mid-1990s. Both models are also congruent in a subsequent drop of the epidemic growth of the analyzed C sub-epidemics and their stabilization until the early 2000s. However, very divergent epidemiological patterns were supported by these two phylodynamic approaches for the most recent stages of the C sub-epidemics, underscoring the importance of their joint use in the reconstruction of past population dynamics of HIV epidemics.
Keywords in PortugueseFilogeografia