Rapid expansion of a HIV-1 subtype F cluster of recent origin among men who have sex with men in Galicia, Spain.

To the Editors: The prevalence of HIV-1 infections among men who have sex with men (MSM) has experienced a notable increase in recent years in many countries, frequently associated with the expansion of local transmission clusters. In Western Europe, these clusters are predominantly of subtype B, but occasional clusters of non–subtype B clades have also been reported among MSM. Here, we report the rapid expansion of a recently originated HIV1 subtype F cluster among MSM in the region of Galicia, Northwest Spain. Since 1999, we regularly process plasma samples from HIV-1–infected individuals, including new HIV-1 diagnoses, attended at public hospitals of Galicia in the cities of Vigo, Pontevedra, Ourense, Lugo, Ferrol, and A Coruña. These samples are routinely analyzed in HIV-1 protease-reverse transcriptase (PR-RT) sequences for detection of antiretroviral drug resistance–associated mutations, subtyping, and determination of phylogenetic relationships. Our previous studies have shown that in this region, as in the rest of Spain and Western Europe, subtype B is the predominant HIV-1 clade, but multiple other variants are also detected. Among non–subtype B genetic forms, from 1999 through 2009, the most prevalent were subtype G and BG recombinant viruses [including circulating recombinant form (CRF) 14_BG], which circulate among the local population. Subtype F viruses represented a very minor proportion of infections, 1.8%, among new HIV-1 diagnoses from 2001 through 2009. However, since 2010, subtype F infections have increased dramatically in Galicia, representing, among new HIV-1 diagnoses, 27.4% in 2010, and 30% in the first 4 months of 2011 (other genetic forms detected in Galicia during this period among new HIV-1 diagnoses were, in 2010, subtype B 57.5%, CRFs 02_AG, 14_BG, and 47_BF 1.9% each, subtypes D and G and CRF01_AE 0.9% each, and unique recominant forms 5.7%; and in the first 4 months of 2011, subtype B 53.3%, subtype C and CRFs 01_AE, 02_AG and 47_BF 3.3% each, and BC recombinants 6.7%). In phylogenetic trees of PR-RT (HXB2 positions 2253–3452), all but 2 HIV-1 subtype F infections newly diagnosed in Galicia in 2010 and the first 4 months of 2011, together with 4 diagnosed in this region in 2009 and 1 in Bilbao (Basque country, North Spain) in 2010, form a strongly supported monophyletic cluster of 41 viruses of F1 subsubtype with a mean intracluster genetic distance of 0.4% (Fig. 1). Through BLAST searches in the Los Alamos HIV Sequence Database and subsequent inclusion in phylogenetic analyses of the highest scoring database sequences, we found 4 viruses closely related to the Galician F1 cluster, 3 of them (PHI_2, PHI_3 and PHI_22) collected in Geneva, Switzerland, in 2005 or 2006, and 1 (BRGO3010) collected in Goiania, Central West Brazil, in 2007 (Fig. 1). An additional subtype F virus (433 odyssee) from France collected in 2006, sequenced only in RT, is also closely related to the Galician F1 cluster (data not shown). Among subtype F viruses sequenced in fulllength genomes deposited in databases, the one most closely related to the Galician F1 cluster is 06BR579, collected in the Brazilian city of Sao Paulo (Fig. 1). All 41 individuals in the Galician F1 cluster are men, 38 of them native Spanish, and, among 40 with known transmission modes, all reported sexual risk exposures, 28 homosexual, 2 bisexual, 3 heterosexual, and 7 nonspecified sexual. At least 6 infections correspond to recent transmissions (less than 6 months since seroconversion). The epicentre of this outbreak is in the province of A Coruña, where 30 (73.2%) individuals reside [20 (48.8%) diagnosed in the city of A Coruña and 10 (24.4%) in Ferrol], and where the 5 earliest cases were diagnosed, although cases were also diagnosed in the 3 other Galician provinces. The spread of this cluster to other areas of Spain seems to be currently limited because among 94 HIV-1 infections newly diagnosed in 2010 in another Spanish region, the Basque Country, only 1 (also a sexually infected man) belonged to the Galician F1 cluster. Among the 5 viruses closely related to the Galician F1 cluster collected outside of Spain, risk exposure data are available for the 3 collected in Switzerland, 2 of which correspond to MSM, and 1 to a heterosexual man. To estimate the date of the most recent common ancestor (MRCA) and to analyze the demographic growth of the Galician F1 cluster, we used a Bayesian Markov Chain Monte Carlo (MCMC) method as implemented in BEAST v1.6.1. Because the evolutionary rate could not be inferred directly from the sequences of the cluster, due to the narrow time span of sample collection, it was estimated using 68 subsubtype F1 PR-RT sequences retrieved from the Los Alamos HIV Sequence Database or obtained by us from viruses sampled between 1993 and 2011 and lacking drug resistanceassociated mutations. In a subsequent analysis, the estimated posterior distribution of the substitution rate was incorporated as a prior distribution to estimate the time of the MRCA of the F1 cluster. The substitution model used Supported by funds through FIS (Fondo de Investigaciones Sanitarias), Ministry of Science and Innovation, Spain, grant PI 080496; European Network of Excellence EUROPRISE (Rational design of HIV vaccines and microbicides), grant LSHP-CT-2006-037611; and Consellería de Sanidade, Government of Galicia, Spain (MVI 1291/08). The authors have no conflicts of interest to disclose. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.jaids.com). Correspondence to: Michael M. Thomson, MD, PhD, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain. e-mail: [email protected]. J Acquir Immune Defic Syndr Volume 59, Number 3, March 1, 2012 Letters to the Editor