Fowke K R, Nagelkerke N J, Kimani J, Simonsen J N, Anzala A O, Bwayo J J, MacDonald K S, Ngugi E N, Plummer F A
Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada.
Lancet. 1996 Nov 16;348(9038):1347-51. doi: 10.1016/S0140-6736(95)12269-2.
There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection.
We did an observational cohort study of incident HIV-1 infection-among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up.
Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections.
We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1.
有间接证据表明，接触HIV-1并不必然导致持续感染。感染易感性的异质性可能归因于保护性免疫。本研究的目的是查明在HIV-1高暴露人群中是否存在对感染具有抵抗力的个体。
1985年至1994年间，我们在肯尼亚内罗毕对424名最初HIV-1血清学阴性的妓女进行了一项关于HIV-1新发感染的观察性队列研究。在研究期间，239名女性血清转化为HIV-1阳性。采用指数、威布尔和混合生存模型来检验随访时间对HIV-1感染发病率的影响。通过Cox比例风险模型研究了通过卖淫接触HIV-1的持续时间对血清转化风险的影响，并对其他已知或疑似的HIV-1新发感染风险因素进行了控制。对43名在随访3年或更长时间后仍保持血清学阴性的持续血清学阴性妓女进行了HIV-1 PCR检测，检测引物为env、nef和vif基因。
对HIV-1血清转化时间的建模显示，HIV-1血清转化的发病率随着暴露时间的延长而降低，这表明HIV-1易感性或对HIV-1的获得性免疫存在异质性。通过卖淫每增加一个加权暴露年，HIV-1血清转化风险降低1.2倍（风险比0.83 [95%可信区间0.79-0.88]，p < 0.0001）。对流行病学和实验室数据的分析表明，持续血清学阴性不能用HIV-1血清学阴性感染或HIV-1感染风险因素的差异（如更安全的性行为或其他性传播感染的发病率）来解释。
我们得出结论，一小部分高暴露个体可能对HIV-1具有天然保护性免疫，对HIV-1具有抵抗力。
