Garland F C, Garland C F, Gorham E D, Brodine S K
Department of Health Sciences, Naval Health Research Center, San Diego, CA 92186-5122, USA.
Ann Epidemiol. 1996 Jul;6(4):341-7. doi: 10.1016/s1047-2797(96)00053-1.
Although human immunodeficiency virus (HIV) infection is progressive, the rate of decline in CD4+ lymphocyte counts varies. The role of immune system components in limiting HIV infection has yet to be defined, but a previous report on the U.S. Navy HIV Seropositive Cohort reported that strong reactivity in the anti-p55 (core precursor), p24 (core) and p53 (reverse transcriptase) Western blot bands was associated with higher CD4+ lymphocyte counts at the first clinical evaluation for HIV. The previous report examined the cross-sectional association between Western blot banding patterns and initial CD4+ lymphocyte counts. This report examines the association between these banding patterns in individuals who progressed rapidly as compared with patterns of patients who did not, based on their trends in repeated CD4+ lymphocyte counts as a marker of progression. Rapid and slower progressors were identified from a cohort of 3414 Navy and Marine Corps personnel who had a first positive HIV Western blot during 1986-1991. For purposes of this study, rapid progressors were defined as individuals whose CD4+ lymphocyte counts declined to < 500 cells/mm3 within 1 year of seroconversion. A total of 325 individuals met these criteria. A comparison group of 63 slower progressors also was identified; this group consisted of those whose CD4+ lymphocyte counts remained at > or = 500 cells/mm3 for a minimum of 5 years of follow-up after their first positive Western blot. Rapid progressors were slightly younger than slower progressors and were more likely to be never married but did not differ significantly from slower progressors in race or sex. Rapid progressors had weaker reactivity in the anti-p55 core precursor (P < 0.0001), p15 core (P < 0.01), gp41 transmembrane (P < 0.01) and p31 endonuclease (P < 0.05) bands on the Western blot. The odds ratio for rapid progressor status associated with weak or absent reactivity was 7.8 in the anti-p55 band and ranged from 2.0 to 3.2 in the anti-p31, p15, and gp41 bands. These associations remained significant after adjustment for age, race, and sex. The p55 association persisted in repeated Western blots during routine clinical evaluation during a period of 5 years after the first positive Western blot. It was concluded that several possible explanations may account for the weaker reactivity of rapid progressors: (i) weak anti-p55 reactivity might have been a marker of early immune system damage; (ii) high concentrations of p55 or related proteins in the serum may have bound the available anti-p55 antibodies in rapid progressors, making them difficult to identify on the Western blot; or (iii) lack of anti-p55, p15, gp41, or p31 reactivity might have allowed more rapid progression.
虽然人类免疫缺陷病毒（HIV）感染是渐进性的，但CD4 +淋巴细胞计数的下降速率各不相同。免疫系统成分在限制HIV感染中的作用尚未明确，但之前一份关于美国海军HIV血清阳性队列的报告指出，在首次HIV临床评估时，抗p55（核心前体）、p24（核心）和p53（逆转录酶）免疫印迹条带的强反应性与较高的CD4 +淋巴细胞计数相关。之前的报告研究了免疫印迹条带模式与初始CD4 +淋巴细胞计数之间的横断面关联。本报告根据重复的CD4 +淋巴细胞计数趋势作为进展标志，研究了快速进展者与未快速进展者的这些条带模式之间的关联。从1986 - 1991年间首次HIV免疫印迹呈阳性的3414名海军和海军陆战队人员队列中确定了快速进展者和进展较慢者。在本研究中，快速进展者定义为血清转化后1年内CD4 +淋巴细胞计数降至<500个细胞/mm3的个体。共有325人符合这些标准。还确定了一个由63名进展较慢者组成的对照组；该组由首次HIV免疫印迹呈阳性后至少随访5年CD4 +淋巴细胞计数保持在>或 = 500个细胞/mm3的个体组成。快速进展者比进展较慢者略年轻，更可能从未结婚，但在种族或性别上与进展较慢者无显著差异。快速进展者在免疫印迹的抗p55核心前体（P < 0.0001）、p15核心（P < 0.01）、gp41跨膜（P < 0.01）和p31核酸内切酶（P < 0.05）条带上的反应性较弱。抗p55条带中与弱反应性或无反应性相关的快速进展者状态的优势比为7.8，抗p31、p15和gp41条带中的优势比在2.0至3.2之间。在调整年龄、种族和性别后，这些关联仍然显著。在首次HIV免疫印迹呈阳性后的5年期间，在常规临床评估的重复免疫印迹中，p55的关联持续存在。得出的结论是，几种可能的解释可以说明快速进展者反应性较弱的原因：（i）抗p55反应性弱可能是早期免疫系统损伤的标志；（ii）血清中高浓度的p55或相关蛋白可能结合了快速进展者中可用的抗p55抗体，使其在免疫印迹上难以识别；或者（iii）缺乏抗p55、p15、gp41或p31反应性可能导致更快的进展。
