Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Protective Effects of IL4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females Nuanjun Wichukchinda a,b , Emi E. Nakayama b , Archawin Rojanawiwat a , Panita Pathipvanich c , Wattana Auwanit a , Suthon Vongsheree a , Koya Ariyoshi d , Pathom Sawanpanyalert a and Tatsuo Shioda b Objective: To evaluate the effect of polymorphisms in interleukin-4 (IL4) and RANTES promoters on disease progression in HIV-1 infected Thais. Design: Antiretroviral (ARV) drug-free HIV-1 infected females from the prospective cohort. Methods: A total of 246 DNA samples were genotyped for IL4 and RANTES promoter polymorphisms by PCR–RFLP. Associations of genotype with HIV-1 disease progression were assessed with respect to baseline clinical data including plasma HIV-1 load, CD4 cell counts, and proportion of symptomatic/AIDS, and survival status during 3 years of follow-up. Results: Patients with homozygous IL4-589T allele showed a significantly lower HIV-1 viral load (P ¼ 0.005) and a higher CD4 cell count (P ¼ 0.003) than the other patients with heterozygous IL4-589C/T or homozygous IL4-589C allele. Kaplan – Meier analysis demonstrated an apparent but insignificant trend towards better survival in homozygous IL4-589T patients. On the other hand, patients with RANTES-28G allele showed a significantly better survival while those with RANTES In1.1C allele without RANTES-28G showed a significantly poorer survival compared with those who did not possess either RANTES In1.1C or RANTES-28G (P ¼ 0.02), although those poly- morphisms only weakly associated with baseline viral load and CD4 cell counts. Conclusions: Our results implicate the significant protective effect of IL4-589T and RANTES-28G on HIV disease progression in Thais. In contrast, RANTES In1.1C without RANTES-28G had an accelerating effect on HIV disease progression. ß 2006 Lippincott Williams & Wilkins AIDS 2006, 20:189–196 Keywords: IL4-589T, RANTES promoter polymorphisms, HIV disease progression, survival, Thailand, viral load, CD4 cells Introduction HIV-1 infected individuals have widely different rates of disease progression. Some infected individuals become symptomatic within 2–3 years while others remain asymptomatic for more than 10–15 years [1]. It is important to investigate factors modulating rates of disease progression for designing novel therapies and vaccines. RANTES is a natural CCR5 ligand and potently inhibits cell entry of HIV-1 that uses CCR5 as a coreceptor From the a National Institute of Health, Department of Medical Sciences, Ministry of Public Health, Nonthaburi, Thailand, the b Research Institute for Microbial Diseases, Osaka University, Osaka, Japan, the c Day Care Center, Lampang Hospital, Lampang, Thailand, and the d AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. Correspondence to T. Shioda, Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita-shi, Osaka, 565-0871 Japan. Tel: +81 6 6879 8346; fax: +81 6 6879 8347; e-mail: shioda@biken.osaka-u.ac.jp Received: 26 May 2005; revised: 9 September 2005; accepted: 27 October 2005. ISSN 0269-9370 Q 2006 Lippincott Williams & Wilkins 189