Dissemination Dynamics of HIV-1 Subtype B Pandemic and Non-pandemic Lineages Circulating in Amazonas, Brazil

The HIV-1 epidemic in the Amazonas state, as in most of Brazil, is dominated by subtype B. The state, nonetheless, is singular for its significant co-circulation of the variants B_CAR, which can mostly be found in the Caribbean region, and B_PAN, a clade that emerged in the United States and aggregates almost the totality of subtype B infections world-wide. The Amazonian HIV-1 epidemic provides a unique scenario to compare the epidemic potential of B_PAN and B_CAR clades spreading in the same population. To reconstruct the spatiotemporal dynamic and demographic history of both subtype B lineages circulating in Amazonas, we analyzed 1,272 HIV-1 pol sequences sampled in that state between 2009 and 2018. Our phylogeographic analyses revealed that while most B_CAR infections resulted from a single successful founder event that took place in the Amazonas state around the late 1970s, most B_PAN infections resulted from the expansion of multiple clusters seeded in the state since the late 1980s. Our data support the existence of at least four large clusters of the pandemic form in Amazonas, two of them nested in Brazil's largest known subtype B cluster (B_BR-I), and two others resulting from new introductions detected here. The reconstruction of the demographic history of the most prevalent B_PAN (n = 4) and B_CAR (n = 1) clades identified in Amazonas revealed that all clades displayed a continuous expansion [effective reproductive number (R _e) > 1] until most recent times. During the period of co-circulation from the late 1990s onward, the R_e of Amazonian B_PAN and B_CAR clusters behaved quite alike, fluctuating between 2.0 and 3.0. These findings support that the B_CAR and B_PAN variants circulating in the Brazilian state of Amazonas displayed different evolutionary histories, but similar epidemic trajectories and transmissibility over the last two decades, which is consistent with the notion that both subtype B variants display comparable epidemic potential. Our findings also revealed that despite significant advances in the treatment of HIV infections in the Amazonas state, B_CAR and B_PAN variants continue to expand and show no signs of the epidemic stabilization observed in other parts of the country.