Meyer L, Magierowska M, Hubert J B, Rouzioux C, Deveau C, Sanson F, Debre P, Delfraissy J F, Theodorou I
AIDS. 1997 Sep;11(11):F73-8. doi: 10.1097/00002030-199711000-00001.
To determine the influence of heterozygosity for the delta 32 mutant CCR-5 allele on HIV-1 disease progression.
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).
The frequency of heterozygosity for the mutant allele was 17% and did not differ according to sex or risk factor of 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 test, 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.
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.
确定δ32突变型CCR - 5等位基因杂合性对HIV - 1疾病进展的影响。
在412名已知血清转化日期的白种人患者（319名男性和93名女性）中，根据C - C趋化因子受体（CCR）- 5基因型分析HIV - 1疾病进展和血清病毒载量，这些患者被纳入SEROCO队列（中位随访时间为74个月）。
突变等位基因杂合性的频率为17%，且在性别或HIV感染风险因素方面无差异。与具有两个功能性等位基因的患者相比，杂合子出现有症状原发性感染的可能性显著降低。在血清转化后的6至24个月平台期，他们的血清病毒载量较低。尽管CD4 +细胞下降速率相似，但这种差异在之后仍然存在。Kaplan - Meier生存曲线显示，在感染后的前7年，杂合子向临床艾滋病进展较慢（P < 0.02），此后两条曲线趋于合并（总体对数秩检验，P = 0.17）。然而，在Cox模型中，与时间的交互项未达到显著水平。进展的总体相对风险为0.67（95%置信区间，0.38 - 1.18），且不受血清转化时年龄或有症状原发性感染调整的影响。在调整早期病毒载量后，相对风险为0.83。尽管治疗相似，但与其他患者相比，杂合子患卡氏肺孢子虫肺炎和弓形虫病作为首个艾滋病定义疾病的可能性较小（0%对24.7%的艾滋病病例，P = 0.04）。
一个CCR - 5基因等位基因的缺失似乎可预防HIV - 1疾病进展，主要是在感染的早期阶段。该缺失的杂合性导致病毒载量持续降低，并且似乎还能预防一些机会性感染。
