Date Published: February 2, 2017
Publisher: Public Library of Science
Author(s): Juan Ángel Patiño-Galindo, Manoli Torres-Puente, María Alma Bracho, Ignacio Alastrué, Amparo Juan, David Navarro, María José Galindo, Concepción Gimeno, Enrique Ortega, Fernando González-Candelas, Zhefeng Meng.
We describe and characterize an exceptionally large HIV-1 subtype B transmission cluster occurring in the Comunidad Valenciana (CV, Spain). A total of 1806 HIV-1 protease-reverse transcriptase (PR/RT) sequences from different patients were obtained in the CV between 2004 and 2014. After subtyping and generating a phylogenetic tree with additional HIV-1 subtype B sequences, a very large transmission cluster which included almost exclusively sequences from the CV was detected (n = 143 patients). This cluster was then validated and characterized with further maximum-likelihood phylogenetic analyses and Bayesian coalescent reconstructions. With these analyses, the CV cluster was delimited to 113 patients, predominately men who have sex with men (MSM). Although it was significantly located in the city of Valencia (n = 105), phylogenetic analyses suggested this cluster derives from a larger HIV lineage affecting other Spanish localities (n = 194). Coalescent analyses estimated its expansion in Valencia to have started between 1998 and 2004. From 2004 to 2009, members of this cluster represented only 1.46% of the HIV-1 subtype B samples studied in Valencia (n = 5/143), whereas from 2010 onwards its prevalence raised to 12.64% (n = 100/791). In conclusion, we have detected a very large transmission cluster in the CV where it has experienced a very fast growth in the recent years in the city of Valencia, thus contributing significantly to the HIV epidemic in this locality. Its transmission efficiency evidences shortcomings in HIV control measures in Spain and particularly in Valencia.
Contrarily to intravenous drug users (IDUs) and heterosexual people (HT), the number of new HIV diagnosis among MSM in the European Union and European Economic Area (EU/EEA) has increased in the last years . This trend is evident in the particular case of Spain, were IDU was consider the main transmission risk during the late 90s. However, in 2013, 51.2% of the 3278 new HIV diagnoses reported in this country occurred among MSMs [2,3]. One of the factors contributing to this resurgence of HIV infections is the continued increase in unprotected anal sex among MSM that occurs since the highly active antiretroviral therapy (HAART) was introduced in 1996 [4,5]. Molecular epidemiology analyses have revealed the vulnerability of MSM to HIV infection in different ways, such as the frequent detection of transmission clusters affecting this risk group [6–10], and the estimation of shorter times between infections compared to those of HTs and IDUs . In Spain, MSMs have been associated with significantly higher levels of local clustering than other risk groups [11,12]. Also, Delgado et al.  recently detected a large HIV-1 subtype F cluster affecting tens of MSM from different Spanish regions, indicating a fast and uncontrolled transmission among recently infected MSM who were unaware of their HIV status.
Among the 1806 HIV-1 pol sequences obtained from different patients in the CV between 2004 and 2014, 1514 were classified as subtype B (prevalence = 83.83%). A potential transmission cluster was found in the initial HIV-1B tree obtained with FastTree (Fig 2), and it was further validated with a ML tree obtained with 633 additional, non-redundant sequences retrieved in a BLAST search and additional controls as detailed in Material and Methods.
We have detected and characterized an HIV-1 subtype B transmission cluster which, affecting 105 patients solely in the city of Valencia, represents one of the largest local HIV-1 transmission clusters described so far in the HIV pandemic history. The report of clusters of similar or larger size is very rare [8,10,13,29,30], especially those that, like the CV-cluster, affect so many people in a single location in such a short time span.