Early protective effect of CCR-5 Delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load
Early protective effect of CCR-5 Delta 32 heterozygosity on HIV-1 disease progression: relationship with viral load
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DOI：
10.1097/00002030-199711000-00001
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发表时间：
1997-09-01
期刊：
影响因子：
3.8
通讯作者：
Drogoul, MP
中科院分区：
文献类型：
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作者：
Meyer, L;Magierowska, M;Drogoul, MP
目的：探讨Delta 32突变体CCR-5等位基因杂合性对HIV-1疾病进展的影响。设计：根据C-C趋化因子受体(CCR)-5基因型分析412名已知血清转化日期的高加索患者（319名男性和93名女性）的HIV-1疾病进展和血清病毒载量，这些患者被纳入SEROCO队列（中位随访74个月）。结果：该突变等位基因的杂合频率为17%，在HIV感染的性别和危险因素方面没有差异。杂合子明显低于具有两个功能等位基因的患者出现症状性原发性感染的可能性。在血清转化后的6- 24个月的平台期，他们的血清病毒载量较低。尽管CD4+细胞的下降速度相似，但这种差异随后持续存在。Kaplan-Meier生存曲线显示，在感染后的前7年，杂合子发展为临床艾滋病的速度较慢（P< 0.02），此后这两条曲线趋于联合（总体对数秩最小值，P = 0.17）。然而，在Cox模型中，与时间的相互作用项没有达到显著性。总体进展的相对危险度为0.67(95%可信区间，0.38-1.18)，不受血清转化年龄调整或症状性原发感染的影响。调整早期病毒载量后的相对危险度为0.83。卡氏肺囊虫肺炎和弓形虫病在杂合子中成为艾滋病首发疾病的可能性低于其他患者（0比24.7%的艾滋病病例，P= 0.04），尽管治疗方法相似。结论：一个CCR-5基因等位基因的缺失似乎可以防止HIV-1疾病的进展，主要是在感染的早期。缺失的杂合性导致持续降低病毒载量，并且似乎也可以防止一些机会性感染。
Objective: To determine the influence of heterozygosity for the Delta 32 mutant CCR-5 allele on HIV-1 disease progression.Design: HIV-1 disease progression and serum viral load were analysed according to the C-C chemokine receptor (CCR)-5 genotype in 412 Caucasian patients (319 men and 93 women) with a known date of seroconversion, who were enrolled in the SEROCO cohort (median follow-up, 74 months).Results: The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor for HIV infection. Heterozygotes were significantly less likely than patients with two functional alleles to have symptomatic primary infection. Their serum viral load was lower during the 6- to 24-month plateau phase after seroconversion. This difference persisted afterwards, although the rate of decline in CD4+ cells was similar. Kaplan-Meier survival curves showed slower progression to clinical AIDS in heterozygotes during the first 7 years following infection (P< 0.02), the two curves tending to join thereafter (overall log-rank lest, P = 0.17). However, the interaction term with time did not reach significance in a Cox model. The overall relative risk of progression was 0.67 (95% confidence interval, 0.38-1.18) and was not influenced by adjustment for age at seroconversion or symptomatic primary infection. After adjustment for early viral load the relative risk was 0.83. Pneumocystis carinii pneumonia and toxoplasmosis were less likely to be the first AIDS-defining illness in heterozygotes than in the other patients (0 versus 24.7% of AIDS cases, P= 0.04), despite similar management.Conclusion: Deletion of one CCR-5 gene allele appears to protect against HIV-1 disease progression, mainly during the early years of the infection. Heterozygosity for the deletion leads to persistently lower viral load, and also seems to protect against some opportunistic infections.