HIV暴露的处理

HIV暴露的处理

Eric S. Daar, M.D.

Chief, Division of HIV Medicine

Harbor-UCLA Medical Center

Professor of Medicine

David Geffen School of Medicine at UCLA

1124 W, Carson St, N-24, Torrance, CA 90502

Phone: (310) 222-2467, Fax: (310) 533-0447

E-mail: EDaar@LABioMed.org

译者：马杰住院医师

北京协和医院内科

Email：pony1980_1999@yahoo.com.cn

审阅者：李敬云教授

解放军军事医学科学院

Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily as a result of sexual or blood exposures, or from an infected mother to her newborn. Prospective randomized trials of post-exposure prophylaxis (PEP) are not practical because the risk of transmission in most settings is low. Consequently, recommendations for PEP are based on limited data from a single case-control study as well as extrapolation from animal models and studies designed to prevent vertical transmission. Guidelines have emerged that suggest how PEP might be utilized in the event of an occupational exposure to HIV-1. These recommendations balance the potential risk of infection occurring after a specific exposure with the likely benefits and adverse effects related to the use of select antiretroviral agents. More recently the Center for Disease Control has updated guidelines for the use of PEP in the setting of non-occupational exposures to HIV-1.

人免疫缺陷病毒-1(HIV-1)的传播主要是经由性活动、血液暴露或者已感染的母亲传染给她婴儿的结果。由于在多数情况下病毒传播的风险度很低，因此进行评估暴露后预防效果的前瞻性随机临床试验是不切实际的。目前推荐的HIV暴露后预防是基于单一的临床试验 (病例-对照)所衍生出的有限数据、来自动物模型的推断和一些预防垂直传播的研究结果。已经提出了在发生职业性HIV暴露后如何进行暴露后预防的指南。这些指南权衡了特定暴露后潜在的感染风险以及选择性使用抗逆转录病毒药物可能的利弊。最近美国疾病控制中心也更新了非职业性HIV-1暴露进行暴露后预防(PEP)的指南。

Timing and Determinants of HIV Infection

HIV transmission occurs when virus-containing fluids such as blood, semen, vaginal secretions, cerebrospinal fluid, or amniotic fluid contact mucous membranes or breaks in the skin. The likelihood of transmission is expected to be closely related to the concentration of virus in the fluid and extent of exposure. Transmission rates vary from greater than 90% for transfusion of blood from an infected person (12), 25-35% for vertical transmission from an untreated infected woman to her newborn (8), 0.1-3% for receptive anal intercourse, to 0.1-0.2% for receptive vaginal intercourse (14, 20, 24, 31, 39). The risk of transmission as a result of oral sex is likely to be even lower (30). Transmission from blood occurs most often among intravenous drug users and healthcare workers. The risk of transmission after a single exposure in these populations is estimated to be approximately 0.5% and depends on the type of exposure (13, 19, 34).

测量和确定HIV感染的时间

当含有病毒的体液如血液、精液、阴道分泌物、脑脊液或羊水等接触粘膜或破损的皮肤时,HIV的传播可发生。感染病毒的可能性与体液中病毒的浓度以及暴露的程度密切相关。不同途径感染率并不相同，输入HIV感染者血液的感染率超过90%(12),未接受治疗的感染HIV的母亲垂直传播给她的婴儿感染率为25-35%(8),肛交接受方为0.1-3%,阴道性交接受方为0.1-3%(14,20,24,31,39)。经口交被传染的可能性会更低（30）。经血液途径感染大部分是发生在静脉毒品使用者和卫生工作人员。在这些人群中，依暴露的情况，一次暴露被感染的风险估计约为 0.5%。(13,19,34)。

The interval between HIV-1 exposure and the onset of viremia has been studied in the simian immunodeficiency virus (SIV) primate model. Spira and colleagues demonstrated that dendritic cells are infected within hours of a mucosal SIV challenge, viral spread to regional lymph nodes occurs within 24 to 48 hours, and viremia is usually detectable within 5 days (33), While these types of studies are not possible in humans, the time frame for HIV-1 infection is probably similar (10). Together, the data from animals and humans suggests that if antiretroviral therapy is to prevent infection it is best initiated within the first few hours of exposure in order to halt the spread to regional lymph nodes and subsequent dissemination.

Review Article: Landovitz RJ, Jagannathan P, Bhatt A, Roland ME. Preventing HIV Infection After a Potential Sexual Exposure. Infect in Med 2007;24:239-246.

从暴露HIV-1的发生到出现病毒血症的时间间隔，以经由灵长类猴免疫缺陷病毒（SIV）模型研究了。Spira 及其同事证实，树突状细胞在粘膜SIV攻击后数小时内即会被感染, 24-48小时内病毒则已蔓延至局部淋巴结，一般于5天内可检测到病毒血症(33) 。然而这些类型的研究不可能在人体进行，然而HIV-1感染的时间表可能与SIV相似(10)。总之，依据动物和人类的数据提示，如果应用抗逆转录病毒治疗来预防感染，最好是在暴露后的最初数个小时内用药，以阻止病毒蔓延至局部淋巴结以及接下来的全身扩散。

综述：Landovitz RJ, Jagannathan P, Bhatt A, Roland ME. Preventing HIV Infection After a Potential Sexual Exposure. Infect in Med 2007;24:239-246.

Risk of Infection Following Occupational Exposure and Rationale for PEP

A case-control surveillance study previously showed that the use of open-label zidovudine (ZDV) resulted in an 81% reduction in transmission among occupationally exposed healthcare workers from France, Italy, United Kingdom and the United States (1). The study also showed that the risk of HIV-1 transmission was significantly increased when the injuries were deep, when there was visible blood on the surface of the transmitting instrument, when the instrument had been previously inserted in the vein or artery of an infected person, and when the source patient died of AIDS within two months of the exposure. All of these factors are likely to be surrogates for exposure to larger amounts of infectious fluid and/or the presence of higher concentrations of virus.

职业暴露后的感染风险和PEP的基本原理

一个早先的病例-对照监测研究显示，在法国、意大利、英国和美国，职业暴露的医疗卫生人员使用开放标签的齐多夫定(ZDV)后减少了81%的病毒感染(1)。研究也显示当伤口很深、当致伤的器械表面有可见的血液、当致伤的器械先前被插入感染者的静脉或动脉，以及在暴露后的两个月内源病人即死于艾滋病（AIDS）时，HIV-1传播的危险性显著升高。所有这些情况都提示暴露于大量传染性体液和/或体液中有高浓度的病毒。

Despite the promising reduction in transmission seen in this case-control study, it is important that clinicians counseling exposed individuals are aware that early experiences with ZDV alone were associated with a high frequency of side effects and early termination of therapy (11, 17, 25, 34). In addition, the efficacy data from this study is limited to only 33 cases, often taken from a different cohort than the 665 control subjects and unlike the prospectively collected data from the control group, some cases were reported retrospectively. Finally, the reported 81% efficacy of PEP is bracketed by wide 95% confidence intervals (48% - 94%) (16). Despite the limitations of the available data statistical models have shown that occupational PEP is potentially cost effective (26), and this management strategy is widely endorsed by the Centers for Disease Control and Prevention (CDC) (7).

尽管在这个病例-对照的研究中看到了病毒的感染的减少,但临床医生在对暴露者进行咨询时应意识到早期单独使用ZDV(齐多夫丁)时，很多人因频繁发生的副作用，以致提前终止治疗,这点是非常重要的(11,17,25,34)。另外，这项研究的有效数据只有来自不同队列的33名病例和665名对照，与前瞻性研究从对照组收集数据的方式不同，有些病例是回顾性的报告。最后，尽管报告的PEP 的有效性达到81%，但其95%的可信区间很宽，是48%-94%（16）。尽管可用的数据有限，统计学模型已经显示职业暴露后预防（PEP）是可能有效的（26），已被美国疾病预防控制预防中心（CDC）广泛认可（7）。

Evaluation of an Exposed Healthcare Worker

In the event of exposure to potentially infectious material, healthcare workers should seek immediate medical attention from clinicians experienced in assessing occupational exposures and in the use of antiretroviral drugs. Those exposed should be questioned as to the circumstances, timing and type of exposure, as well as what is known of the HIV-1 infection status of the source person. Exposed individuals should also undergo hepatitis B virus (HBV) post-exposure management.

对发生暴露的卫生工作人员的评估

一旦暴露于可能的传染性材料，卫生工作人员应立即寻求有评估职业暴露以及使用抗逆转录病毒药物方面经验的医师来诊治。医师应详细询问环境、暴露的时间和类型、以及所能了解到的源病人的HIV-1感染状态。暴露的个体也应接受乙型肝炎（HBV）暴露后的处理方案。

The risk of infection is expected to correlate with the type and volume of potentially infectious fluid that the healthcare worker is exposed to and the nature of the exposure. If the exposure was to blood, the degree of infectivity may be inferred from the source patient's viral load. For example, if percutaneous exposure occurs with a solid bore needle or other sharp instrument the actual amount of infectious material inoculated is relatively small, in contrast to the larger inoculums delivered by a hollow bore needle. Similarly, exposure to intact skin poses relatively little risk compared to abraded skin. The risk of transmission after exposure of mucous membranes is less well defined but is a recognized alternate route of occupational HIV-1 transmission (6).

感染的风险与卫生工作人员所暴露的传染性体液类型、体液量和其当时暴露的性质有关。如果暴露于血液，可根据源病人的病毒载量推断感染的风险。例如，如果经皮暴露是由实心针头或其他利器引起的，实际上其接种的传染性物质较少，而空心针头传递的病毒量要大得多。类似的情况,完整皮肤暴露后感染的风险比破损皮肤要小。经粘膜暴露感染的风险尚不清楚，然而这也被认为是职业性HIV-1感染另外一种途径(6)。

Evaluation of Source Person

The source person of an occupational exposure should be evaluated for epidemiological, clinical, and laboratory evidence of HIV-1, HBV, and hepatitis C virus (HCV) infection (4, 7). The source person's overall risk of being infected with HIV-1 should also include the possibility of a recent exposure history or the presence of a syndrome consistent with primary HIV-1 infection (9, 38). The presence of such symptoms in an HIV-antibody-negative source person may require further testing, such as with a p24 antigen or plasma HIV-1 RNA assay, with the continuation of PEP for the healthcare worker. If the source’s HIV status is unknown, rapid HIV-antibody testing should be performed on the source, if possible, in order to minimize the duration of unnecessary antiretroviral therapy (32). The source should also be evaluated for the likelihood of harboring drug-resistant HIV-1. There is strong evidence that drug resistant virus is transmitted by sexual exposure and is likely to also occur in the setting of an occupational exposure (21, 40). Therefore, whenever possible the source should be questioned about previous antiretroviral therapy as well as known pre-existing drug resistance.

对源病人的评估

对职业暴露的源病人应进行流行病学、临床及实验室检查的评估以寻找HIV-1、HBV、HCV病毒感染的证据 (4,7)。对病源病人总体HIV感染风险的评估也应包括最近的暴露史或急性HIV-1感染的临床表现(9, 38)。HIV抗体阴性的源病人如出现这些症状需要作进一步检测，例如P24抗原和血浆HIV-1 RNA，同时卫生工作人员应持续进行暴露后预防（PEP）。如不知道源病人HIV感染的状态，如果可能应对病源病人进行快速HIV抗体测定，旨在尽量缩短非必要抗逆转录病毒治疗的时间(32)。也应对病源病人进行是否可能存在耐药HIV-1毒株的评估。大量证据证明，耐药病毒可通过性活动，同样也可发生在职业暴露后传播(21, 40)。因此，应尽可能询问源病人以前抗逆转录病毒治疗的情况以及以前是否存在耐药病毒。

Recommendations for PEP Following Occupational Exposure

The CDC provides guidelines for PEP in cases of percutaneous injuries (Table 1) and exposures to mucous membrane and non-intact skin (Table 2) (7). Whether or not to institute therapy depends on the significance of the exposure, whereas decisions about the type of drug therapy generally depends on the severity of the exposure, such as the amount of infectious fluids the person is exposed to, the amount of virus in the fluids, such as viral load in blood, and the likelihood of drug resistance in the source. The type of antiretroviral therapy recommended in guidelines is based upon the goal of balancing the risk of toxicity with the potential benefit. Assistance in decision-making is also available through a direct consultation 24-hours-per-day from PEPLine, a joint program of the University of California San Francisco and San Francisco General Hospital Community Provider AIDS Training Project and Epidemiology and Prevention Interventions Center at 1-888-HIV-4911 (Table 3).

职业暴露后推荐的PEP

CDC提供了经皮(表1）、粘膜以及不完整皮肤暴露（表2）后的PEP指南 (7)。是否开始治疗取决于暴露的性质，而选择治疗的药物一般取决于暴露的严重程度，例如暴露的传染性体液的量、其中含有的病毒量，如血液中的病毒载量，以及源病人可能存在的耐药病毒。指南中所推荐的抗逆转录病毒治疗的类型是基于对药物所致毒性的风险和可能获益的权衡。可以通过一个24小时PEP专线（1-888-HIV-4911）的直接咨询协助决定治疗方案，这是加利福尼亚旧金山大学、旧金山总医院开展的社区提供AIDS培训计划以及流行病与预防干预中心联合项目提供的(表3)。

Recommended therapeutic options for occupational PEP include a basic regimen of 2 nucleoside reverse transcriptase inhibitors (NRTIs) for relatively low-risk exposures and an expanded regimen of three drugs for higher-risk exposures. Based upon recent guidelines for PEP along with extrapolation from current treatment recommendations for chronically HIV-1-infected adolescents and adults the basic regimen should generally be one that would include lamivudine (3TC, Epivir^TM) or emtricitabine (FTC, Emtriva^TM) in combination with zidovudine (ZDV, Retrovir^TM), stavudine (d4T, Zerit^TM) or tenofovir DF (TDF, Viread^TM) (3, 7). Although most recent PEP guidelines have not specifically included TDF, this agent is now one of the preferred choices for the treatment of chronically HIV-1-infected individuals, as well as being highly efficacious in SIV models of PEP. In fact, in theory it may act more quickly than other NRTIs because it requires the addition of only two, rather than three phosphates to become activated (36, 37). In contrast, the most recent PEP guidelines have included d4T and didanosine (ddI, Videx^TM) as an options (7) which has more recently been proven to be associated with increased toxicity and is generally no longer recommended as a treatment option for HIV infection (3).

推荐的职业暴露后预防方案包括针对相对低风险暴露的2个核苷类逆转录酶抑制剂(NRTIs)的基础方案，以及针对高风险暴露的3个药物的扩大方案。基于近期发布的PEP指南并参考当前的青少年、成人慢性HIV-1感染者治疗的推荐，职业暴露后基础预防方案一般包括拉米夫定(3TC, Epivir^TM) 或恩曲他滨 (FTC, Emtriva^TM) 联合齐多夫定 (ZDV, Retrovir^TM)、司他夫定(d4T, Zerit^TM) 或泰诺福韦 (TDF, Viread^TM) (3, 7)。尽管最近多数的PEP指南没有特别包括TDF，这是一种目前首选的治疗慢性HIV-1感染的药物，在SIV感染模型上也显示出很好的PEP效果。事实上，从理论上讲TDF可能比其他NRTIs起效更快，因为该药的活化只需要结合两个磷酸盐而不是三个(36, 37)。相反的，最新的PEP指南包括了d4T 和去羟肌苷 (ddI, Videx^TM)(7)，这两药近期被证明与增加的药物毒性有关，一般情况下也不再推荐用于HIV感染的治疗用药(3)。

Recommended “expanded regimens” can be created by adding a protease inhibitor (PI) or a nonnucleoside analogue reverse transcriptase inhibitor (NNRTI) to the dual NRTI regimens outlined above. Recommended PIs have included indinavir (IDV, Crixivan^TM) or nelfinavir (NFV, Viracept^TM) but in the current era the use of other agents frequently suggested for the treatment of chronically infected individuals can be considered (3). Many experts would also recommend a ritonavir (RTV, Norvir^TM)-boosted PI regimen to achieve higher PI drug levels, particularly if drug resistance is a concern. NNRTI-containing PEP regimens are potent, fast acting, easy to administer, and have yielded promising results in animal models (15). They also do not require intracellular phosphorylation to become active. However, it is important to note that nevirapine (NVP, Viramue^TM) is not recommended in this situation due to reports of severe hepatotoxicity and skin reactions in persons taking this agent as part of a PEP regimen (5). Due to the teratogenicity of efavirenz (EFV, Sustiva^TM), it should be used with caution in those of child-bearing potential.

推荐的“扩大方案”，是在两个NRTI类药物的基础方案中加入一种蛋白酶抑制剂（PI）或一种非核苷类逆转录酶抑制剂（NNRTI）。推荐的蛋白酶抑制剂包括茚地那韦(IDV,CrixivanTM)或奈非那韦(NFV,ViraceptTM)，也可以考虑其他的治疗HIV-1慢性感染者的药物(3)。许多专家也推荐利托那韦(RTV, Norvir^TM)—加强的PI方案，以达到更高的PI浓度，特别是在怀疑耐药毒株传播时。包含NNRTI的PEP方案效力高，起效快，方便使用，在动物实验中得了到令人信服的结果(15)。NNRTI类药物的活化不需要细胞内的磷酸化。然而，重要的一点是应注意到奈韦拉平(NVP, Viramue^TM) 未被推荐用于“扩大方案”中，因为有报道该药作为PEP用药时出现严重的肝脏毒性及皮肤反应(5)。由于依法韦仑(EFV, Sustiva^TM)的致畸性，用于可能妊娠的病人时应予注意。

Regardless of the regimen used treatment should be initiated as soon as possible after an exposure and be continued for 4 weeks with appropriate follow-up, although this duration is based on limited animal data (36). The CDC guidelines list several situations for which expert consultation for HIV-1 PEP is advised: (i) delayed presentation (i.e., more than 24-36 hours post exposure), (ii) an unknown source, (iii) known or suspected pregnancy in the exposed person, (iv) documented or suspected antiretroviral drug resistant virus in the source person, and (v) toxicity of the initial PEP regimen (7).

尽管治疗方案的不同，PEP方案应在暴露后尽快启动并需在合适的随诊情况下持续4周，然而这个服药周期只是基于有限的动物实验数据(36)。美国CDC的指南列出了需要咨询专家后进行HIV-1 PEP的数种情况：(i) 暴露超过 24-36小时后来诊，(ii) 暴露源不明，(iii)暴露者已知或可能存在妊娠，(iv) 源病人有记录的或可疑对抗逆转录病毒药物耐药，(v)初始PEP方案引起毒性作用(7)。

Follow-up of HIV-1-Exposed Individuals

Healthcare workers exposed to potentially infectious material should be offered psychological counseling and support. If PEP is started the exposed individual should return in two weeks to have a complete blood count and hepatic enzyme measurements. Following completion of prophylaxis they should return for hepatic transaminase levels and HIV antibody testing 6, 12, and 24 weeks after exposure. Exposed individuals should also be advised to use precautions to prevent secondary transmission throughout the follow-up period. Furthermore, they should be counseled as to the symptoms of primary HIV-1 infection and the need to return immediately for HIV antibody and virologic testing if they develop such symptoms. However, unless primary infection is being considered, virologic testing such as measures of plasma HIV-1 RNA should be discouraged because of the potential for false positives (9, 29). To reduce psychological stress during the course of follow-up, individuals should also be told that most seroconversions occur during the first 6 weeks after an exposure, and that the likelihood of infection declines with time.

HIV-1暴露者的随诊

应给予暴露于潜在传染性物质的卫生工作人员心理咨询和支持。如果开始PEP，暴露者应在两周内随诊，进行全血及肝酶指标检测。在完成整个预防方案后，应在暴露后的第6、12、24周随诊行肝酶及HIV抗体测定。建议暴露者在随诊期间采取措施预防病毒的二代传播。此外，应告诉暴露者HIV-1早期感染后可能出现的症状，如果出现这些症状应立即行HIV抗体及病毒学测定。然而，除非怀疑HIV早期感染，否则不鼓励进行病毒学检查，如HIV-1 RNA测定，因为可能会出现假阳性结果(9, 29)。为减轻随诊期间的心理负担，应告诉暴露者大多数血清转换发生在暴露的最初6周后，感染的可能性随着时间的推移而降低。

Non-Occupational Exposure

The clinical data supporting PEP for non-occupational exposures are scarce and most evidence is derived from studies of experimental mucosal and intravenous challenges in primates using NRTIs. One of the few studies demonstrating protection was in a macaque model using SIV and TDF with optimal protection occurring when therapy was started within 24 hours of exposure (36, 37). Although studies in humans of occupational exposure and vertical transmission suggest potential benefits of PEP, individuals need to recognize the limitations of extrapolating these experiences to PEP in the non-occupational setting. Nevertheless, updated guidelines have recently been released by the Department of Health and Human Services in the United States that provide guidance for those managing these exposed individuals (2). Although definitive efficacy trials are unlikely to ever exist, pilot data has demonstrated the feasibility of providing non-occupational PEP in the community (18). Moreover, modeling has suggested that such treatment may be cost-effective when the source is known to be HIV1-infected or after high risk exposures, such as unprotected receptive anal intercourse with a homosexual or bisexual man of unknown serostatus (27).

非职业性暴露

支持非职业性PEP的临床数据很少,多数证据来自粘膜或静脉攻毒的使用NRTIs的灵长类动物实验。只有少数几项研究证明非职业性PEP具有保护作用，其中的一个是SIV攻击的短尾猿模型，在暴露后24小时内使用TDF取得了理想的保护效果(36, 37)。尽管在人类职业暴露及垂直传播的研究中显示出PEP的好处，但根据这些经验推断非职业性暴露PEP的效果是不够的。尽管如此，最近美国卫生及人类服务部发布了最新的指南，提供了针对非职业暴露的处理指导(2)。尽管目前还没有来证实非职业暴露PEP有效的临床试验，但初步的数据证实在社区提供非职业性暴露PEP是可行的(18)。而且，模型研究显示，已知暴露源是HIV-1感染者或发生高危暴露时，例如同HIV感染状态不明的男性进行同性或双性无保护肛交的接受方，采取暴露后预防措施是具有较好的成本效益(27)。

Individuals who present for care after a potential sexual, percutaneous, or other non-occupational exposure should be interviewed as to the type of their exposure, and counseled as to the potential risks and benefits of PEP in this setting, as well as ways to prevent future exposures. Underlying depression and/or substance abuse that may contribute to people repeatedly placing them at risk should be identified and individuals referred to community resources to assist in dealing with these underlying problems.

对那些在性活动、经皮肤暴露或其他非职业性暴露后担忧可能感染了HIV的人，应了解他们暴露的类型，告诉他们在这种情况下进行PEP可能的利弊，以及避免再次发生暴露的方法。应广泛宣传那些可能将人们反复置于HIV感染危险之下的抑郁和／或药物滥用的行为，有这些行为的人应向社区寻求帮助以解决这些问题。

Non-Occupational Exposure: Evaluation of Source Person and Type of Exposure

The risk of infection during sex is likely to be related to several factors, including the partner's viral load, type of bodily fluid to which the exposure occurred, and presence of genital inflammation (20, 28, 39). The risk of transmission will also vary based upon the type of sexual exposure. The greatest risk is associated with receptive anal intercourse (0.1-3%) and vaginal intercourse (0.1-0.2%) (24, 39). There is a lower but real risk associated with oral sexual exposures (30). The risk of transmission may be further increased if sexual exposure is to blood, such as during menses in HIV-infected women or with associated trauma. Moreover, the presence of genital ulcer disease or inflammatory genital lesions may further increase the risk of transmission. Needle sharing is also associated with an estimated 0.67% chance of infection, approximating that seen with percutaneous exposures in occupational settings (19, 34). An assessment of the source should include their history of antiretroviral therapy use in order to estimate the potential that the person may harbor drug-resistant virus. This assessment is generally done by history since treatment decisions need to occur long before resistance testing could be made available.

非职业性暴露：对源病人及暴露类型的评估

性活动感染HIV的风险可能与几个因素有关，包括性伴的病毒载量、暴露的体液类型以及合并的性病(20,28,39)。传播的危险也会因性活动的暴露类型不同而有差异。危险最大的是肛交(0.1-3%) 和阴道性交的接受方(0.1-0.2%)(24, 39)。口交的危险要低一些，但确实是有危险的(30)。如果性活动时暴露在血液中，传播的危险更大，例如同女性HIV感染者在月经期性交，或在性活动中出现损伤。此外，生殖器溃疡或生殖器炎症会进一步增加传染的风险。共用针头的感染率约为0.67%，与经皮职业暴露的感染率大致相当(19, 34)。对源病例的评估应包括他们抗逆转录病毒治疗的用药史,以推断是否可能存在的耐药病毒。由于耐药检测需要很长时间，临床上又需要尽快作出治疗的决定，耐药评估主要通过了解源病人的治疗史完成。

Considerations for Treatment

Those who present after a non-occupational exposure should be interviewed as to the circumstances and timing of the exposure. Animal data supports initiation of PEP within the first two hours with diminished value after 24-36 hours. Current guidelines recommend PEP in those presenting within 72 hours of a substantial exposure to a source partner known to be HIV-infected. Substantial risk is defined as exposure of vagina, rectum, eye, mouth or other mucous membranes, as well as to non-intact skin or percutaneously to potentially infectious material such as blood, semen, vaginal secretions, rectal secretions, breast milk or other body fluids that are visibly contaminated with blood. In the case where the source partner is not known the decision to start PEP should be individualized based upon the type of exposure and what is known of the potential risk factors of the source person. In contrast, those presenting more than 72 hours after such an exposure should not necessarily be offered such treatment (2). Recommendations further support the use of PEP in those victims of assault that include substantial exposure to potentially infectious fluids.

治疗需要考虑的事项

应同那些发生非职业性HIV暴露的人进行访谈，了解他们暴露的环境和暴露的时间。动物实验的数据支持在暴露最初的两个小时内开始PEP，暴露后24-36小时后开始PEP效果将会失降低。目前的指南推荐那些与确诊的HIV感染者发生真正暴露的人应在72小时内进行PEP。这些真正的危险因素被确定为阴道、直肠、眼睛、口腔及其他粘膜组织、以及经破损皮肤或皮下与可能有传染性的物质，如血液、精液、阴道分泌物、直肠分泌物、乳汁或其他明显被血液污染的体液接触。一旦出现性伴来源不明的情况，应该由暴露的类型以及所了解到的该性伴可能有的危险因素来决定个体化的PEP方案。如暴露已超过72小时，就没有必要再进行PEP(2)。指南进一步支持了那些真正暴露在可能有传染性液体的人应进行PEP。

Subjects should be informed of the experimental nature of PEP in this setting, as well as the risks and benefits of therapy as outlined in the sections related to occupational exposures. They should also be offered follow-up testing and counseling regarding behavior modification, adherence to antiretroviral therapy, and the symptoms of acute HIV-1 infection. There have also been concerns raised as to whether the availability of PEP may lead to increased risk-taking behavior (22). While this concern emphasizes the need for behavioral counseling, reassurance comes from studies showing that the provision of non-occupational PEP has not resulted in increased high-risk behavior (23). Finally, those younger than age 16 should be evaluated, prior to initiation of therapy by a pediatrician or family physician familiar with the use of antiretroviral therapy in children and adolescents. This initial evaluation might include investigation of possible child abuse and deal with issues of consent for medical care of minors.

应告诉那些发生非职业性HIV暴露的人，PEP带有实验性质，有利，也有弊。还应该为他们提供随访检测和关于行为改变、抗逆转录病毒治疗依从性及HIV-1感染急性期症状的咨询。使用PEP是否可能导致危险行为增加，这是人们十分关注的问题(22)。强调在施行PEP的同时必须进行行为咨询，有研究证实非职业性的PEP并未导致高危行为的增加(23)。最后，对年龄小于16岁的人员在开始治疗前应由熟悉儿童及成人抗逆转录病毒治疗的儿科大夫或家庭医师进行评估，评估的内容应包括调查可能存在的虐待儿童情况及治疗是否需要未成年人同意。

Antiretroviral Therapy for Non-Occupational PEP

The administration of antiretroviral therapy after non-occupational exposure to HIV-1 is of unproven efficacy, many clinicians are routinely asked to provide such treatment. As outlined in recent guidelines, therapeutic options largely parallel those of current recommendations for treatment of chronically HIV-1-infected adolescents and adults (2). Although it is acknowledged that in this setting there is no evidence that three drug regimens are better than two, preferred options include PI-based treatment with lopinavir/ritonavir (LPV/r, Kaletra^TM) and ZDV with either 3TC or FTC, or these NRTIs with one of several alternative PIs. Another preferred option includes EFV with either ZDV or TDF along with either 3TC or FTC, remembering that EFV should be used with caution in women of child-bearing potential. As with occupational PEP, NVP should be avoided in this setting. In addition, exposed individuals should be assessed for sexually transmitted diseases and the need for emergency contraception (35). Finally, as described for occupational PEP follow-up should be performed to assure that infection by HIV, HBV and HCV does not occur as well as for drug-related toxicity.

非职业性PEP的抗逆转录病毒治疗

HIV-1的非职业性暴露后给予抗逆转录病毒治疗尚未证实有效，但许多医师常常被要求提供这样的治疗。近期PEP指南中提出的可选择的治疗方案大体上同当前推荐用于青少年、成人HIV-1慢性感染者的治疗方案类似(2)。尽管这种情况下没有证据证明3药的方案优于2药的方案，首选的方案包括以PI为基础的治疗联合洛匹那韦/利托那韦 (LPV/r, Kaletra^TM)； ZDV 联合 3TC 或 FTC；或这些NRTIs联合PIs中的一个。另一个首选的方案包括EFV和ZDV或 TDF同时联合3TC 或 FTC，记住可能妊娠的女性病人使用EFV时应予注意。同在职业性PEP中一样，NVP应避免应用在有妊娠可能的女性病人中。另外，对暴露者应进行关于性传播疾病以及是否需要紧急避孕的评估(35)。最后，应进行同职业性PEP相同的随诊，以保证未被传染乙型肝炎和丙型肝炎病毒，并检测药物所致的毒性。

Conclusion

There are animal and human data that suggest the provision of antiretroviral therapy after occupational and non-occupational exposure may reduce the risk of HIV-1 transmission. Based upon these data the CDC and other agencies have developed guidelines for when therapy should be considered in each of these settings. Recommendations focus on providing treatment to those with a true risk of acquiring HIV-1-infection, and when there is believed to be potential benefit of such therapy, such as when initiated within 72 hours of the exposure. Since there are no randomized-controlled studies defining the utility of PEP, yet alone the optimal treatment regimen to use, guidelines have approximated those for the treatment of chronically HIV-1-infected adolescents and adults, although avoiding drugs with substantial short-term toxicity. Nevertheless, it remains important to counsel subjects as to the risks of such treatment. Moreover, the initial meeting with an exposed individual should be used as an opportunity to address behavioral changes, both in the work place and the community that might result in avoiding exposures in the future.

结论

有动物及人体的数据显示在职业性及非职业性暴露后使用抗逆转录病毒治疗可以减少HIV-1感染的风险。基于这些数据,CDC及其他部门已经提出了在各种情况下何时开始治疗的指南。指南的焦点是，给真正有HIV-1感染的风险的人提供治疗，以及何时治疗可能获得预防HIV感染的效果，例如在暴露后72小时内何时开始治疗。由于没有随机-对照的研究来确定PEP的效果，随着理想方案的使用，尽管避免了药物所致的短期毒性作用，PEP指南已与青少年及成人HIV-1慢性感染者的治疗方案相似。然而，向暴露者告知这些治疗可能存在的风险仍然很重要。此外，不论在工作场所还是在社区，应将与暴露者的初次会面作为劝导其改变危险行为的机会，以避免将来再次发生暴露事件。

Tables

Table 3. Occupational Exposure Management Resources

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