Tracing the Impact of Public Health Interventions on HIV-1 Transmission in Portugal Using Molecular Epidemiology

Abstract

Background: Estimation of temporal changes in human immunodeficiency virus (HIV) transmission patterns can help to elucidate the impact of preventive strategies and public health policies.

Methods: Portuguese HIV-1 subtype B and G pol genetic sequences were appended to global reference data sets to identify country-specific transmission clades. Bayesian birth-death models were used to estimate subtype-specific effective reproductive numbers (Re). Discrete trait analysis (DTA) was used to quantify mixing among transmission groups.

Results: We identified 5 subtype B Portuguese clades (26-79 sequences) and a large monophyletic subtype G Portuguese clade (236 sequences). We estimated that major shifts in HIV-1 transmission occurred around 1999 (95% Bayesian credible interval [BCI], 1998-2000) and 2000 (95% BCI, 1998-2001) for subtypes B and G, respectively. For subtype B, Re dropped from 1.91 (95% BCI, 1.73-2.09) to 0.62 (95% BCI,.52-.72). For subtype G, Re decreased from 1.49 (95% BCI, 1.39-1.59) to 0.72 (95% BCI, .63-.8). The DTA suggests that people who inject drugs (PWID) and heterosexuals were the source of most (>80%) virus lineage transitions for subtypes G and B, respectively.

Conclusions: The estimated declines in Re coincide with the introduction of highly active antiretroviral therapy and the scale-up of harm reduction for PWID. Inferred transmission events across transmission groups emphasize the importance of prevention efforts for bridging populations.

Keywords: HIV; Portugal; epidemiology; harm reduction; phylodynamics; reproductive number; transmission groups.

Figure 1.

Diagram describing the process of selecting human immunodeficiency virus type (HIV-1) subtype B and G sequences for the analysis. ML, maximum likelihood; SH, Shimodaira-Hasegawa.

Figure 2.

Top, Maximum likelihood (ML) phylogenetic trees reconstructed from the combined data sets, showing human immunodeficiency virus type subtype B (left) and subtype G (right). The black color indicates Portuguese sequences and is used to highlight their position on the global diversity trees. The highlighted clades are the clades of at least 10 sequences with a within-clade genetic distance <6% and a Shimodaira-Hasegawa–like statistical support >90%. Bottom, ML phylogenetic trees of the identified phylogenetic clades. The colors of the tips represent the transmission group of a patient from whom the sequence was sampled.

Figure 3.

A and C, Effective reproductive number (R_e) estimates obtained using the constant rate birth-death model (ie, model 1; constant R_e) under different assumptions of infectious period (6 months–5 years; rate of becoming uninfectious, 2.0–0.2) for subtypes B (A) and G (C). The vertical lines in the middle of the violin plots represent the interquartile range. The filled with color violin plots (A) represent the value of R_e assuming the infectious period of 2 years. The horizontal red dotted line represents the epidemiological threshold (R_e = 1). B and D, R_e estimates obtained using the birth-death skyline model (ie, model 2) over 10 equidistant intervals between the tree height and the most recent tip in the analysis for subtype B (B) and G (D), assuming an infectious period of 2 years. The shaded area represents the 95% Bayesian credible interval. The horizontal red dotted line represents the epidemiological threshold (R_e = 1). Vertical lines correspond to the time of introduction of major interventions to prevent human immunodeficiency virus infection. HAART, highly active antiretroviral therapy.

Figure 4.

Effective reproductive number (R_e) estimates obtained using the constant-shift-constant model (ie, model 3; 2 intervals) and the estimated time of change in the rate of epidemic spread for both subtypes. The violin plots of the R_e distribution before and after the time of the estimated change in viral spread rate are illustrated for both subtypes. The shaded area represents the 95% Bayesian credible interval. The horizontal red dotted line represents the epidemiological threshold (R_e = 1).

Figure 5.

Results of the discrete trait analysis (DTA) for both human immunodeficiency virus subtypes. Top, Molecular clock phylogenetic trees reconstructed for subtype B clade 5 (left) and the subtype G clade (right). The color of the branches corresponds to the transmission group state; the width of the branches corresponds to the posterior probability support for the indicated transmission group state. Bottom, Results of the DTA for both subtypes, considering 5 and 3 transmission groups (k = 5 and k = 3, respectively). The colors represent the transmission group of a patient from whom the sequence was sampled. From left to right, y-axes show the proportion of migration events attributed to a transmission group, reconstructed using robust counts approach (numbers correspond to the number of sequences in the transmission group); the rescaled association index (AI); and Bayes factor (BF) values for the significant virus migration pathway. The size of the circles corresponds to the number of sequences in the analysis; the width of the arrows corresponds to the number of migration events for the corresponding pathways. HET, heterosexual; MSM, men who have sex with men; MTC, mother-to-child transmission; PWID, people who inject drugs.