Yang C, Nguyen L, Chaowanachan T, Vanichseni S, Li M, Mock PA, Griensven FV, Martin M, Sangkum U, Choopanya K, Tappero JW, Lal RB, Hu DJ; Conference on Retroviruses and Opportunistic Infections (11th : 2004 : San Francisco, Calif.).
Program Abstr Conf Retrovir Oppor Infect 11th 2004 San Franc Calif. 2004 Feb 8-11; 11: abstract no. 401.
CDC, Atlanta, GA, USA
BACKGROUND: The discovery that chemokine receptors are used by HIV-1 as co-receptors for cellular entry led to the finding that host genetic factors can influence the susceptibility to HIV-1 infection and disease progression. However, most studies have focused on European or North American populations. In the present study, we investigated the effects of CCR5 promoter human haplogroups (HH) on HIV-1 disease progression among HIV-infected injecting drug users (IDU) with known dates of seroconversion followed in a prospective cohort.METHODS: By using PCR-RFLP and sequencing, we genotyped 106 seroconverter specimens for CCRb2-64I, CCR5-D32, and 7 CCR5 promoter SNP and classified them into 9 CCR5 promoter human haplogroups (HHA to HHE, HHF*1, HHF*2, HHG*1, and HHG*2). Survival curves and adjusted Cox proportional hazards models were used to assess the effect of haplogroups on HIV-1 viral load and on time to CD4+ T-cell count decline to < 200 cells/(L.RESULTS: The most common CCR5 promoter human haplogroups were HHC (61.8%), followed by HHE (15.6%) and HHF*2 (14.6%). HHE was associated with faster disease progression (p = 0.02) and a nearly 2-fold increased risk (adjusted RH: 1.88, 95% CI: 1.05 to 3.36) for rapid CD4+ T-cell decline. However, other human haplogroups were not significantly associated with differences in disease progression.CONCLUSIONS: Our data provide the first evidence that the CCR5 HHE is associated with more rapid HIV-1 disease progression among Thais. Despite previous reports of slower disease progression associated with HHF*2-bearing CCR2b-64I, we observed no protective effect in this IDU population. Differences in association with HIV-1 disease progression by CCR5 promoter human haplogroups highlight the need for additional studies in Asian populations.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Antigens, CD4
- Asian Continental Ancestry Group
- CD4 Lymphocyte Count
- Disease Progression
- Genotype
- HIV Infections
- HIV Seropositivity
- HIV-1
- Humans
- Longitudinal Studies
- Promoter Regions (Genetics)
- Proportional Hazards Models
- Receptors, CCR5
- Receptors, Chemokine
- Thailand
- genetics
- immunology
Other ID:
UI: 102271362
From Meeting Abstracts