title: HIV-1 coreceptor tropism in India: increasing proportion of X4-tropism in subtype C strains over two decades.
abstract: BACKGROUND
  Recent studies show an increase in the frequency of X4-tropism in African HIV-1 subtype C (HIV-1C) strains and among Indian children with a longer duration of infection. There is limited availability of comprehensive data on HIV-1 tropism in Indian HIV-1C strains and impact on coreceptor antagonist drug susceptibility. We evaluated coreceptor tropism trends over 2 decades and maraviroc resistance-associated V3 loop substitutions among the Indian HIV-1C strains.
  
  
  METHODS
  We performed genotypic tropism testing using Geno2Pheno10% on primary samples from patients (n = 224) and on Indian HIV-1C sequences downloaded from the Los Alamos database (n = 528, 1991-2010). We also studied maraviroc resistance-associated substitutions in R5-tropic HIV-1C (n = 992) and subtype B sequences (n = 576).
  
  
  RESULTS
  Among primary samples, 88% belonged to HIV-1C and 11.2% was predicted as X4-tropic, with higher prevalence noted among patients from north-eastern India (19.1%) and significant association with intravenous drug users (P = 0.04). X4-tropism prevalence was higher among antiretroviral therapy-experienced (18.8%) compared with antiretroviral therapy-naive patients (9.1%). Indian database HIV-1C sequences showed X4-tropism at 4%. An increase in the X4 tropism frequency was seen over the years 1991 (1.6%) through 2012 (10%). We found a high frequency of 19T substitution (826/992; 83.3%) among HIV-1C V3 loop compared with subtype B.
  
  
  CONCLUSIONS
  The predominance of R5-tropism in Indian HIV-1C strains despite a marginal temporal increase in X4-tropism prevalence highlights the likely effectiveness of coreceptor antagonists in India. Our frequent observation of common maraviroc resistance-associated substitutions among Indian R5-tropic HIV-1C raises the possibility that they may be natural polymorphisms, indicating the need for further elucidation.
authors.affiliation: *Division of Public Health and Infections, St. John's Research Institute, Bangalore, India; †Department of Microbiology, St. John's Medical College, Bangalore, India; ‡Hematology Research Unit, Division of Molecular Medicine, St. John's Research Institute, Bangalore, India; §Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; ‖Virology-II, National Institute of Immunology, New Delhi, India; ¶Department of Pediatrics, St. John's Medical College Hospital, Bangalore, India; and #Division of Global Health, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Soham
authors.initials: S
authors.lastname: Gupta
authors.forename: Ujjwal
authors.initials: U
authors.lastname: Neogi
authors.forename: Hiresave
authors.initials: H
authors.lastname: Srinivasa
authors.forename: Akhil C
authors.initials: AC
authors.lastname: Banerjea
authors.forename: Anita
authors.initials: A
authors.lastname: Shet
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents; D002648:Child; D002675:Child, Preschool; D003510:Cyclohexanes / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007194:India; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015728:Receptors, HIV / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology; D056189:Viral Tropism; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D015728:Receptors, HIV; D014230:Triazoles; D000077592:Maraviroc