title: The epidemiology and clinical correlates of HIV-1 co-receptor tropism in non-subtype B infections from India, Uganda and South Africa.
abstract: BACKGROUND
  The introduction of C-C chemokine receptor type-5 (CCR5) antagonists as antiretroviral therapy has led to the need to study HIV co-receptor tropism in different HIV-1 subtypes and geographical locations. This study was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.
  
  
  METHODS
  HIV-1-infected patients were recruited into this prospective, cross-sectional, epidemiologic study from HIV clinics in South Africa, Uganda and India. Patients were infected with subtypes C (South Africa, India) or A or D (Uganda). HIV-1 subtype and co-receptor tropism were determined and analyzed with disease characteristics, including viral load and CD4(+) and CD8(+) T cell counts.
  
  
  RESULTS
  CCR5-tropic (R5) HIV-1 was detected in 96% of treatment-naïve (TN) and treatment-experienced (TE) patients in India, 71% of TE South African patients, and 86% (subtype A/A1) and 71% (subtype D) of TN and TE Ugandan patients. Dual/mixed-tropic HIV-1 was found in 4% of Indian, 25% of South African and 13% (subtype A/A1) and 29% (subtype D) of Ugandan patients. Prior antiretroviral treatment was associated with decreased R5 tropism; however, this decrease was less in subtype C from India (TE: 94%, TN: 97%) than in subtypes A (TE: 59%; TN: 91%) and D (TE: 30%; TN: 79%). R5 virus infection in all three subtypes correlated with higher CD4(+) count.
  
  
  CONCLUSIONS
  R5 HIV-1 was predominant in TN individuals with HIV-1 subtypes C, A, and D and TE individuals with subtypes C and A. Higher CD4(+) count correlated with R5 prevalence, while treatment experience was associated with increased non-R5 infection in all subtypes.
authors.affiliation: Pfizer Inc., New York, NY 10017, USA.
authors.forename: Quazi
authors.initials: Q
authors.lastname: Ataher
authors.forename: Simon
authors.initials: S
authors.lastname: Portsmouth
authors.forename: Laura A
authors.initials: LA
authors.lastname: Napolitano
authors.forename: Sybil
authors.initials: S
authors.lastname: Eng
authors.forename: Anna
authors.initials: A
authors.lastname: Greenacre
authors.forename: Andrew
authors.initials: A
authors.lastname: Kambugu
authors.forename: Robin
authors.initials: R
authors.lastname: Wood
authors.forename: Sharlaa
authors.initials: S
authors.lastname: Badal-Faesen
authors.forename: Randy
authors.initials: R
authors.lastname: Tressler
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism; D013019:South Africa / Q000453:epidemiology; D014454:Uganda / Q000453:epidemiology; D056189:Viral Tropism; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; C527276:CXCR4 protein, human; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011991:Receptors, Virus