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CCR5 promoter human haplogroups associated with HIV-1 disease progression in Thai injection drug users

Nguyen, Lilya; Li, Minga; Chaowanachan, Thanyananb; Hu, Dale Ja; Vanichseni, Suphakc; Mock, Philip Ab; van Griensven, Fritsa,b; Martin, Michaela,b; Sangkum, Udomsakd; Choopanya, Kachitc; Tappero, Jordan Wa,b; Lal, Renu Ba; Yang, Chunfua

Epidemiology & Social

Background: An evolutionary-based analysis of the CC chemokine receptor 5 gene (CCR5) promoter region has identified nine stable human haplogroups, within which certain haplogroups appear to influence HIV-1 disease progression differentially among Caucasians and African-Americans.

Objective: To assess the influence of CCR5 haplogroups on HIV-1 disease progression in a Thai population.

Design: Haplogroup analysis of HIV-1-seropositive injection drug users (IDU) participating in a prospective cohort study in Bangkok. All were documented seroconverters with a median follow-up time of 3.5 years (range, 0.2–7.0).

Methods: From a cohort of 130 IDU, 106 (81.5%) were genotyped for the CCR2b-64I, CCR5-Δ32 and seven CCR5 promoter alleles constituting the CCR5 haplogroups. Survival curves and adjusted Cox proportional hazards models were used to assess the effect of haplogroups on the time from HIV-1 infection until CD4 count < 200 × 106 cells/l.

Results: The most common CCR5 haplogroups were HHC (61.8%), followed by HHE (15.6%) and HHF*2 (14.6%). HHE was associated with an accelerated CD4 count decline to < 200 × 106 cells/l (adjusted relative hazard, 1.88; 95% confidence interval, 1.05–3.36; P = 0.02).

Conclusions: This is the first evidence that the CCR5 haplogroup E speeds the decline of the CD4 cell count and may lead to accelerated disease progression among HIV-infected Thais. These new observations highlight the need for additional studies involving populations in Asia.

From the aCenters for Disease Control and Prevention, Atlanta, Georgia, USA, bThai MOPH-US CDC Collaboration, Nonthaburi, cBangkok Vaccine Evaluation Group, Bangkok, dBangkok Metropolitan Administration, Bangkok, Thailand.

Requests for reprints to: Dr C. Yang, HIV Immunology and Diagnostics Branch, NCHSTP, Centers for Disease Control and Prevention, 1600 Clifton Rd NE, MS D-12, Atlanta, Georgia 30333, USA.

Received: 26 January 2004; revised: 19 March 2004; accepted: 20 April 2004.

© 2004 Lippincott Williams & Wilkins, Inc.