title: Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000-2010.
abstract: BACKGROUND
  Most of the non-B HIV-1 subtypes are predominant in Sub-Saharan Africa and India although they have been found worldwide. In the last decade, immigration from these areas has increased considerably in Spain. The objective of this study was to evaluate the prevalence of non-B subtypes circulating in a cohort of HIV-1-infected immigrants in Seville, Southern Spain and to identify drug resistance-associated mutations.
  
  
  METHODS
  Complete protease and first 220 codons of the reverse transcriptase coding regions were amplified and sequenced by population sequencing. HIV-1 subtypes were determined using Stanford University Drug Resistance Database, and phylogenetic analysis was performed comparing multiple reported sequences. Drug resistance mutations were defined according to the International AIDS Society-USA.
  
  
  RESULTS
  From 2000 to 2010 a total of 1,089 newly diagnosed HIV-1-infected patients were enrolled in our cohort. Of these, 121 were immigrants, of which 98 had ethical approval and informed consent to include in our study. Twenty-nine immigrants (29/98, 29.6%) were infected with non-B subtypes, of which 15/29 (51.7%) were CRF02-AG, mostly from Sub-Saharan Africa, and 2/29 (6.9%) were CRF01-AE from Eastern Europe. A, C, F, J and G subtypes from Eastern Europe, Central-South America and Sub-Saharan Africa were also present. Some others harboured recombinant forms CRF02-AG/CRF01-AE, CRF2-AG/G and F/B, B/C, and K/G, in PR and RT-coding regions. Patients infected with non-B subtypes showed a high frequency of minor protease inhibitor resistance mutations, M36I, L63P, and K20R/I. Only one patient, CRF02_AG, showed major resistance mutation L90M. Major RT inhibitor resistance mutations K70R and A98G were present in one patient with subtype G, L100I in one patient with CRF01_AE, and K103N in another patient with CRF01_AE. Three patients had other mutations such as V118I, E138A and V90I.
  
  
  CONCLUSIONS
  The circulation of non-B subtypes has significantly increased in Southern Spain during the last decade, with 29.6% prevalence, in association with demographic changes among immigrants. This could be an issue in the treatment and management of these patients. Resistance mutations have been detected in these patients with a prevalence of 7% among treatment-naïve patients compared with the 21% detected among patients under HAART or during treatment interruption.
authors.affiliation: Laboratory of Immunovirology, Infectious Diseases Service, Instituto Ramón y Cajal de Investigaciones Cientificas (IRYCIS), Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: de Felipe
authors.forename: Pilar
authors.initials: P
authors.lastname: Pérez-Romero
authors.forename: María
authors.initials: M
authors.lastname: Abad-Fernández
authors.forename: Felipe
authors.initials: F
authors.lastname: Fernandez-Cuenca
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Martinez-Fernandez
authors.forename: Mónica
authors.initials: M
authors.lastname: Trastoy
authors.forename: Rosario Del Carmen
authors.initials: Rdel C
authors.lastname: Mata
authors.forename: Luis F
authors.initials: LF
authors.lastname: López-Cortés
authors.forename: Manuel
authors.initials: M
authors.lastname: Leal
authors.forename: Pompeyo
authors.initials: P
authors.lastname: Viciana
authors.forename: Alejandro
authors.initials: A
authors.lastname: Vallejo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D016000:Cluster Analysis; D024882:Drug Resistance, Viral; D054242:Emigrants and Immigrants; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D015995:Prevalence; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D016333:HIV Protease; C514803:p16 protease, Human immunodeficiency virus 1