Phylodynamic and Phylogeographic Profiles of Subtype B HIV-1 Epidemics in South Spain

PLoS One. 2016 Dec 21;11(12):e0168099. doi: 10.1371/journal.pone.0168099. eCollection 2016.

Abstract

Background: Since 1982, HIV-1 epidemics have evolved to different scenarios in terms of transmission routes, subtype distribution and characteristics of transmission clusters. We investigated the evolutionary history of HIV-1 subtype B in south Spain.

Patients & methods: We studied all newly diagnosed HIV-1 subtype B patients in East Andalusia during the 2005-2012 period. For the analysis, we used the reverse transcriptase and protease sequences from baseline resistance, and the Trugene® HIV Genotyping kit (Siemens, Barcelona, Spain). Subtyping was done with REGA v3.0. The maximum likelihood trees constructed with RAxML were used to study HIV-1 clustering. Phylogeographic and phylodynamic profiles were studied by Bayesian inference methods with BEAST v1.7.5 and SPREAD v1.0.6.

Results: Of the 493 patients infected with HIV-1 subtype B, 234 grouped into 55 clusters, most of which were small (44 clusters ≤ 5 patients, 31 with 2 patients, 13 with 3). The rest (133/234) were grouped into 11 clusters with ≥ 5 patients, and most (82%, 109/133) were men who have sex with men (MSM) grouped into 8 clusters. The association with clusters was more frequent in Spanish (p = 0.02) men (p< 0.001), MSM (p<0.001) younger than 35 years (p = 0.001) and with a CD4+ T-cell count above 350 cells/ul (p<0.001). We estimated the date of HIV-1 subtype B regional epidemic diversification around 1970 (95% CI: 1965-1987), with an evolutionary rate of 2.4 (95%CI: 1.7-3.1) x 10-3 substitutions/site/year. Most clusters originated in the 1990s in MSMs. We observed exponential subtype B HIV-1 growth in 1980-1990 and 2005-2008. The most significant migration routes for subtype B went from inland cities to seaside locations.

Conclusions: We provide the first data on the phylodynamic and phylogeographic profiles of HIV-1 subtype B in south Spain. Our findings of transmission clustering among MSMs should alert healthcare managers to enhance preventive measures in this risk group in order to prevent future outbreaks.

MeSH terms

  • Adult
  • Bayes Theorem
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / cytology
  • Demography
  • Female
  • Genotype
  • HIV Infections / diagnosis
  • HIV Infections / epidemiology*
  • HIV Infections / transmission
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Homosexuality, Male
  • Humans
  • Likelihood Functions
  • Male
  • Middle Aged
  • Phylogeny
  • Sequence Analysis, RNA
  • Spain / epidemiology
  • pol Gene Products, Human Immunodeficiency Virus / chemistry
  • pol Gene Products, Human Immunodeficiency Virus / genetics
  • pol Gene Products, Human Immunodeficiency Virus / metabolism

Substances

  • pol Gene Products, Human Immunodeficiency Virus

Grants and funding

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funded by National Plan of I+D+i (RD12/0017/006), Health institute Carlos III(ISCIII), PI12/01053 (General Ministry of Evaluation and European Fund of Regional Development-FEDER), granted to FGG. Ministry of Health of Andalusia (AC-0082-2013), granted to FGG.