Temporal trends in the Swedish HIV-1 epidemic: increase in non-B subtypes and recombinant forms over three decades

Abstract

Background: HIV-1 subtype B (HIV-1B) still dominates in resource-rich countries but increased migration contributes to changes in the global subtype distribution. Also, spread of non-B subtypes within such countries occurs. The trend of the subtype distribution from the beginning of the epidemic in the country has earlier not been reported in detail. Thus the primary objective of this study is to describe the temporal trend of the subtype distribution from the beginning of the HIV-1 epidemic in Sweden over three decades.

Methods: HIV-1 pol sequences from patients (n = 3967) diagnosed in Sweden 1983-2012, corresponding to >40% of patients ever diagnosed, were re-subtyped using several automated bioinformatics tools. The temporal trends of subtypes and recombinants during three decades were described by a multinomial logistic regression model.

Results: All eleven group M HIV-1 subtypes and sub-subtypes (78%), 17 circulating recombinant forms (CRFs) (19%) and 32 unique recombinants forms (URF) (3%) were identified. When all patients were analysed, there was an increase of newly diagnosed HIV-1C (RR, 95%CI: 1.10, 1.06-1.14), recombinants (1.20, 1.17-1.24) and other pure subtypes (1.11, 1.07-1.16) over time compared to HIV-1B. The same pattern was found when all patients infected in Sweden (n = 1165) were analysed. Also, for MSM patients infected in Sweden (n = 921), recombinant forms and other pure subtypes increased.

Significance: Sweden exhibits one of the most diverse subtype epidemics outside Africa. The increase of non-B subtypes is due to migration and to a spread among heterosexually infected patients and MSM within the country. This viral heterogeneity may become a hotspot for development of more diverse and complex recombinant forms if the epidemics converge.

Figure 1. Distribution of HIV-1 subtypes in Sweden between 1983 and 2012.

Final dataset included pol sequences (length >500 nt) from 3967 HIV-1 infected patients. HIV-1 subtyping was determined by three methods (see method section). The sequences were designated as pure subtypes [A (A1 and A2), B, C, D, F (F1 and F2), G, H, J, and K], circulating recombinant forms (01_AE, 02_AG, 03_AB, 06_cpx, 10_CD, 11_cpx, 12_BF, 13_cpx, 18_cpx, 20_BG, 24_BG, 25_cpx, 33_01B, 34_01B, 37_cpx) and unique recombinant forms (URFs).

Figure 2. Proportions and predicted proportions of newly diagnosed HIV-1 subtype B (B), subtype C (C), recombinant forms (REC) and other subtypes (other) by year of diagnosis.

Dotted lines represent actual prevalence in each year, while the smooth lines represent the predicted prevalence. Multinomial logistic regression model adjusted for year of diagnosis was used.

Figure 3. Types and mosaic pattern of HIV-1 unique recombinant forms identified in Sweden.

A. Proportion of recombinant forms was identified based on REGAv3, COMET and RIP 3.0 followed by bootscan analysis incorporated in REGAv3 and SimPlot analysis. B. Mosaic pattern of URFs identified by REGAv3 and SimPlot. Major URFs (A1C, A1D, BC, A1G) which have HXB2 positions 2253 to 3260 and had minimum degenerate bases (≤5) were used for bootscan analysis (n = 43) implemented in Rega v3 with 400 bp window size and 20 bp step size and SimPlot analysis with 300 bp window size and 20 bp step size. The reference sequences were selected for SimPlot analysis is based on the recombinant pattern. Upper bar presents HXB2 co-ordinate.