Human immunodeficiency virus type 1 (HIV-1) subtype B epidemic in Panama is mainly driven by dissemination of country-specific clades

Abstract

The Human immunodeficiency virus type-1 (HIV-1) subtype B is the most predominant clade in Central America; but information about the evolutionary history of this virus in this geographic region is scarce. In this study, we reconstructed the spatiotemporal and population dynamics of the HIV-1 subtype B epidemic in Panama. A total of 761 HIV-1 subtype B pol sequences obtained in Panama between 2004 and 2013 were combined with subtype B pol sequences from the Americas and Europe. Maximum Likelihood phylogenetic analyses revealed that HIV-1 subtype B infections in Panama derived from the dissemination of multiple founder viruses. Most Panamanian subtype B viruses (94.5%) belong to the pandemic viral strain proposed as originated in the US, whereas others (5.5%) were intermixed among non-pandemic Caribbean strains. The bulk (76.6%) of subtype B sequences from Panama grouped within 12 country-specific clades that were not detected in other Central American countries. Bayesian coalescent-based analyses suggest that most Panamanian clades probably originated between the early 1970s and the early 1980s. The root location of major Panamanian clades was traced to the most densely populated districts of Panama province. Major Panamanian clades appear to have experienced one or two periods of exponential growth of variable duration between the 1970s and the 2000s, with median growth rates from 0.2 to 0.4 year(-1). Thus, the HIV-1 subtype B epidemic in Panama is driven by the expansion of local viral strains that were introduced from the Caribbean and other American countries at an early stage of the AIDS pandemic.

Figure 1. ML phylogenetic tree of HIV-1 subtype B pol (∼1000 pb) sequences circulating in Panama (n = 761), and representative sequences of the B_PANDEMIC (US = 465, France = 344) and the B_CAR (Caribbean = 238) clades.

Branches are colored according to the geographic origin of each sequence, as indicated at the legend (top left). Red shaded boxes highlight the position of the twelve major Panamanian HIV-1 subtype B clades (B_PA-I to B_PA-XII). The number of sequences and the aLRT support values for each clade are indicated at bottom. Asterisk indicates the node of the B_PANDEMIC clade. The tree was rooted using HIV-1 subtype D reference sequences. The branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site.

Figure 2. ML phylogenetic tree of HIV-1 subtype B pol (∼1000 pb) sequences circulating in Panama (n = 761) and other Central American countries (n = 694).

The branches are colored according to the geographic origin of each sequence, as indicated at the legend (top left). Red shaded boxes highlight the position of the twelve Panamanian HIV-1 subtype B clades (B_PA-I to B_PA-XII). Gray shaded box highlights the position of the major Central American clade (B_CAM). The aLRT support values for each clade are indicated at bottom. The tree was rooted using HIV-1 subtype D reference sequences. The branch lengths are drawn to scale with the bar at the bottom indicating nucleotide substitutions per site.

Figure 3. Time-scaled Bayesian MCMC tree of the major HIV-1 subtype B Panamanian clades (B_PA-I to B_PA-XII) and reference subtype D sequences.

Branches are colored according to the clade classification as indicated in the legend. Black key circles indicate the positions of nodes corresponding to the MCRA of each clade. The median T_MRCA (with the corresponding 95% credibility interval in parenthesis) of each clade is indicated at bottom. Branch lengths are depicted in units of time (years). The tree was automatically rooted under the assumption of a relaxed molecular clock.

Figure 4. Spatial dissemination of HIV-1 Panamanian clades of large size (B_PA-I to B_PA-IV) across country districts.

Lines between districts represent branches in the Bayesian MCC tree along which location transitions occur. Lines were colored according to the source location as indicated in the legend at top. Dashed lines indicate those location transitions associated to nodes with low location probability support (<0.60). AN, Anton; BT, Bocas del Toro; CHE, Chepigana; CO, Colon; DA, David; KY, Kuna Yala; MU, Muna; NU, Nurum; PED, Pedasí; PEN, Penonome; PI, Pinogana; PSM, Panama and San Miguelito (east Panama province); RE, Renacimiento; SA, Santiago; TO, Tonosí; WP, west Panama province.

Figure 5. Demographic history of HIV-1 Panamanian clades of large size (B_PA-I to B_PA-IV).

Effective number of infections (y-axis; log₁₀ scale) through time (x-axis; calendar years) estimated using Bayesian skyline (A, C, E and G) and logistic (B, D and F) or exponential (H) growth coalescent models are shown for each of the four HIV-1 Panamanian clades. Median estimates of the effective number of infections (solid line) and 95% HPD intervals of the estimates (dashed lines) are shown in each graphic. The median growth rate (with the corresponding 95% credibility interval in parenthesis) of each clade estimated under logistic or exponential growth model is indicated in the upper left corner.