HIV感染者的体重下降和消瘦

译者：陈蓉蓉博士

中国协和医科大学

北京协和医院感染科

北京市东城区帅府园1号

100730

Email: zhangyao1@gmail.com

As has been true with so many infectious diseases, it has been hoped that improvement in the therapy of HIV will eliminate weight loss and wasting as complications of HIV. In this chapter, we hope to convince the reader that even in the era of successful highly active antiretroviral therapy (HAART), weight loss and wasting remain significant clinical problems.

　　虽然HIV的治疗已取得了长足的进步，处理HIV感染者的体重下降和消瘦在今天仍然相当困难。

Initial reports evaluating the nutritional status of HIV infected subjects reported a strong association between body weight and mortality, with death occurring at 66% of ideal body weight (8, 26, 35, 72). Body cell mass or lean body mass comprises the body’s active cellular components and is of primary importance for quality of life, functional capacity and survival. These initial reports showed a greater loss of lean body mass than fat stores, with values 54% of normal at death (35, 36).

　　早期的研究显示HIV感染者的体重和死亡率之间有明显的相关性，患者死亡时的平均体重降为理想体重的66%(8, 26, 35, 72)。而代表机体细胞活性成分、对个体生活质量和功能状态具有重要作用的体细胞质量（body cell mass）和去脂肪体重（lean body mass）下降更加明显。在這些早期的研究報告指出，在HIV感染者死亡时，其体重降为标准值的54%(35, 36)。

Current evidence indicates that overall body composition may be more important than weight in effecting outcome and that weight alone is not a reliable marker of nutritional status (19, 21, 33, 48, 55). Both body fat and lean body mass are depleted in HIV and it appears the pattern of loss may vary with body composition at baseline and disease course (19, 49). Subjects having a higher percent body fat (>15%) at baseline lost more fat than lean body mass and those with <15% baseline fat lost more lean body mass than fat mass (24). Although decreases in lean body mass have been shown to be greater in all patients during secondary infections, those patients with greater fat reserves were able to depend on stored fat to a greater degree (33). Some studies have shown a similar pattern of greater reliance on fat stores in HIV infected women (21). Whether this is secondary to increased fat stores at baseline or hormonal control is unknown. Only in the late stages of HIV wasting did women show significant loss of lean body mass, amenorrhea and decreased muscle mass. However, a recent publication by Tang, et al (62) suggests that weight loss was the best predictor of death in an HIV infected cohort, and was more sensitive than lean body mass.

　　然而体重并不是反应机体营养状态的唯一指标，身体的结构成分（overall body composition）对预后也有很大影响(19, 21, 33, 48, 55)。在HIV感染者中，脂肪（body fat）和非脂肪成份的减少速度因人而异，随患者基础的身体构成成份比例和疾病的不同阶段而变化(19, 49)。例如，基础（baseline）体脂含量>15%的患者会丢失更大比例的脂肪，而体脂含量<15%的患者丢失更大比例的非脂肪体重(24)。尽管从整体上讲，继发的机会性感染会导致患者丢失更多的去脂肪体重，但我们看到更多脂肪储备将有利于减缓非脂肪体重的丢失(33)。对女性HIV感染者的研究也显示类似的趋势(21)。只有在HIV感染末期，妇女才会出现明显的去脂肪体重的丢失、闭经和肌肉成份的减少。这种现象的原因目前还不明确。然而，2002年Tang等人的研究队列报道(62)体重减轻是预测HIV感染者死亡的最好指标，比使用去脂肪体重來預測更为敏感。

Data from the Adult and Adolescent HIV Disease Project, a National Surveillance Project with a large and demographically diverse study population (N= 46, 678), found the incidence of wasting syndrome as defined by Center for Disease Control (CDC) AIDS Surveillance case definition (see Table 1) declined between 1992 through 1999 (11). The incidence of opportunistic infections was high at or after a diagnosis of wasting syndrome occurred. The Multicenter AIDS Cohort Study examined the incidence and predictors of wasting syndrome over calendar time also using the CDC definition case definition (58). Characteristics of persons diagnosed with wasting changed over time, with all symptoms (anemia, fever, fatigue, thrush) still reported in the HAART era, but at a lower rate. Diarrhea was found to be reported at a similar rate as prior to HAART suggesting it continues to play a major role in current wasting syndrome.

　　涵盖广泛人群的研究（Adult and Adolescent HIV Disease Project，共包括46678人）数据显示，根据CDC标准定义的消耗综合征（定义见表1）的发病率在1992年到1999年间逐步下降(11)；机会性感染发生率在消耗综合征诊断时或诊断后达到高峰。另一个采用CDC标准的大型研究也显示HAART抗病毒治疗方案出现后消耗综合征仍然存在，但发病率降低(58)。腹泻发生率并没有受到HAART治疗的影响，這提示腹泻在消耗综合征的发生扮演了一亇重要的角色。

The incidence and prevalence of weight loss and wasting were examined in a prospective, longitudinal cohort of HIV infected adults (69). These study participants make study visits every six months for measurement of height, weight, body composition, and Resting Energy Expenditure (REE). For the purposes of this study, wasting was defined in three ways; first, as a measured 10 % decrease in body weight from the time of study entry, second, as a loss of 5% of measured body weight between any 2 six months visits that persists for at least one year, or a fall in the body mass index to below 20 kg/m². Eighty-eight (13.9%) of 633 enrolled participants met one of the definitions of wasting at the time they enrolled in the study and were excluded from the analysis; a total of 469 participants had sufficient data to determine these wasting outcomes. A total of 139 participants (29.5%) of the cohort met one or more of the definitions of wasting after study entry. Sixty eight patients (14.5 %) met a definition of wasting by experiencing a weight loss of 10% of body weight since study entry; 36 patients (7.7%) had a body mass index that fell below 20 kg/m²; and 75 patients (15.9%) of the cohort met a definition of wasting by losing more than 5% of body weight within a 6 month period that was sustained for more than 1 year. Of these patients, 320 (68%) used HAART; 64 participants began HAART while they were followed by the study, 31 (48%) of these met one of the definitions of wasting after they began HAART. One hundred (31%) of the remaining participants who have used HAART also met a definition of wasting. Twenty-six percent of the individual participants who had never used HAART also met a definition of wasting, a percentage slightly less than that seen in the participants who did use HAART or who developed wasting after beginning HAART. The incidence of wasting is very high in this cohort; the cumulative prevalence of wasting is even higher at 35.8% (69). An additional analysis from this same cohort suggested that the frequency of weight loss has not changed over time. When rates of weight loss were assessed yearly from 1995 to 2003, rates of loss of 5% of body weight per year increased over the time period studied, even after the introduction of HAART (63).

　　Wanke CA等人的前瞻性队列研究中每六个月对患者进行身高、体重、机体组成和静息状态能量消耗（REE，Resting Energy Expenditure）的测量。消耗（wasting）定义包括：1.体重较入组时减轻10%以上；2. 两次随访之间体重减轻大于5%并至少持续一年以上；3. 体重指数（BMI，body mass index）小于20kg/m²。共计633位参与者中，有88人因在研究开始已满足以上的诊断标准（13.9%）被排除，最终的入组人数为469人。研究结束时，共139人（29.5%）满足1个以上的上述诊断标准，满足第1、2、3项标准的情况分别为68人（14.5%）、75人（15.9%）、36人（7.7%）。共320人（68%）接受HAART治疗；64人在入组之后才开始HAART治疗，其中31人（48%）最终诊断为消耗状态。入组前已开始使用HAART治疗者当中有100位（31%）出现消耗状态。未接受HAART治疗的患者中有26%出现消耗状态，其發生率低于其它两组(入組前已用HAART和入組後才开始HAART)。该研究中，消耗状态的总体发病率是很高，累积患病率更达到35.8% (69)。对研究数据的另一个分析提示体重减轻的頻率并没有随时间的进展而改善。1995年到2003年之间，即使在HAART疗法被应用之后，其年均体重减轻5%的患者仍在逐年增加(63)。

A total of 58% (289/633) of this same cohort lost a mean of 4 kg between any two study visits; 1.3 kg of this loss was lean body mass; 2/3 or 2.7 kg was fat mass. A further cross-sectional analysis of data from the same cohort demonstrated that weights of patients in the study were a mean of 1.9 kg lower for each 100 cell decrement in CD₄ cells (17). Sixty-eight percent of decrease in weight in these patients was fat mass, whereas only thirty-two percent was lean body mass. These data suggest that while weight loss and wasting are extremely common, both may be predominantly loss of fat rather than lean, as some studies early in the HIV epidemic have suggested. Another publication from this cohort, using the same definitions of wasting, found that while weight loss and wasting remained common, the number of AIDS defining conditions (ADCs) is decreasing. The contribution of ADCs to the development of wasting was relatively small (70).

　　在这个研究中有58%（289/633）的患者每半年体重减轻4千克，其中1.3千克是去脂肪体重，而2.7千克（2/3）为脂肪的丢失。CD4细胞计数每减少100对应个体重下降1.9千克，这其中68%是脂肪，而仅32%为去脂肪体重。这些数据和以往的HIV流行病学调查都表明消瘦是普遍的，脂肪的丢失比去脂肪体重的丢失更为明显。研究数据还显示，相对于消瘦而言，艾滋病特征性疾病（ADCs， AIDS defining conditions）发生率却在下降，因而推测ADCs对于消耗状态的作用较小(70)。

Studying this same cohort, Tang, et al found weight loss of ≥ 10% from baseline or previous visit was significantly associated with a four-to-six fold increase in mortality in the era of HAART (62). This underscores the concept that weight loss in HIV associated individuals continues to be associated with death. Therefore, the diagnosis and appropriate treatment of wasting syndrome is essential. It has recently been recommended that the current CDC definition of wasting (see Table 1) be expanded (23). Predictors of wasting pre HAART may no longer be reliable as exclusively predicting wasting (23). Defining levels of risk for nutritional complications is essential for identification of individuals requiring nutrition intervention to prevent wasting.

　　分析同一个研究的数据，Tang等人发现体重减轻大于10%以上（相对于感染HIV之前或前一次检查）者在HAART治疗期间死亡率比其他人高4-6倍(62)，说明HIV感染者的減重与死亡的相关性。因此，对消耗综合征的诊断及治疗是重要的。有学者建议将目前CDC关于消耗的定义加以扩展（见表1）。由於HAART的影响，針对消耗综合征的诊断在HAART出现以前所使用的预测方式可能已不适用(23)。于臨床上，鋻定患者在营養有関併发征風險的程度並進行营養補給來防止消耗综合征的发生是必要的。

The other major nutritional /metabolic issue in HIV, the lipodystrophy syndrome, may be confused with or confuse the recognition of weight loss and wasting. As patients with lipodystrophy may lose weight, gain weight, or remain weight stable, it may be difficult to accurately differentiate weight loss/wasting from the fat atrophy seen with lipodystrophy. While a standard case definition does not exist and the distinctions may truly be obscure in some patients, appropriate categorization will be possible in most patients. It is important to distinguish between voluntary nutritional weight loss and involuntary or intentional weight loss. Those patients with wasting/ weight loss will have progressive unintentional decrease in weight, a decrease in lean and/or fat mass by bioelectrical impedance, and a decrease in mid-arm circumference. Patients with fat atrophy or mixed fat atrophy/ fat accumulation may have no consistent alteration in weight. These individuals may have fat atrophy in the face, extremities, and buttocks, with or without central fat accumulation. Therefore patients with fat atrophy will likely have decreases in mid arm circumference with no change or increase in waist circumference. Unlike patients without body fat redistribution, in whom bioelectrical impedance provides an easy and reliable means to determine body composition, in those patients with fat redistribution, bioelectrical impedance does not provide an accurate measure of body composition (16, 21).

　　HIV感染者的其它营养代谢性问题、如脂肪营养障碍综合征（lipodystrophy syndrome）可能会与消耗相混淆而影响后者的诊断。脂肪营养障碍者可能出现体重增加、减少，或维持不变。另外，需要区分患者的体重减轻是否是有意向的。消耗的患者表现为进展性的非意向性的体重减轻，即，包括去脂肪体重的减轻和脂肪的丢失，检查可发现生物电阻抗的降低和臂围的减小。脂肪营养不良或混合型脂肪萎缩脂肪堆积患者通常没有持续性的体重改变。他们可能在面部、四肢和臀部出现脂肪萎缩，伴/不伴中心性脂肪堆积。因而，脂肪营养不良的患者可能会出现臂围减少而腰围没有变化甚或增加。在没有出现脂肪重新分布的患者中，生物电阻抗可以作为测定机体组分的一个简单而可信的方法，然而一旦有脂肪重新分布，生物电阻抗方法的准确性就受到了影响(16, 21)。

It appears that malnutrition frequently develops gradually during the course of HIV and may be detected prior to weight loss by evaluating changes in body composition. Wasting/weight loss may occur more rapidly in the context of significant diarrhea, anorexia, secondary infection, or virologic failure. Both magnitude and pattern of weight loss appear to be predictive of changes in body composition and two primary patterns have been described (40, 73). The first is the patient who presents with rapid, severe weight loss most often associated with non-gastrointestinal infections. These patients are acutely catabolic and frequently regain weight quickly once the infection resolves. However, these patients may not return to their ideal or premorbid weight. The second pattern is the patient with chronic relentless weight loss, which is generally associated with gastrointestinal manifestation and a state of semi starvation. Response to nutrition therapy in these patients depends on the ability to provide adequate calories while limiting gastrointestinal symptoms. The magnitude of loss is considerable with each and the mechanisms, which are discussed in detail below, may occur simultaneously in an individual. In addition, the conflicting outcomes of studies evaluating nutrition and HIV reflect the diverse clinical spectrum of the disease.

　　对HIV感染者，营养不良通常是逐步发展的过程。测定机体组分的变化有助于在出现体重减轻之前早发现营养不良。严重的腹泻、食欲下降、继发感染或抗病毒治疗失败都会明显加快体重减轻的发生。其中有两种模式比较常见 (40, 73)。第一类是与非胃肠道感染相关的体重迅速减轻。这些病人处于分解代谢亢进期，一旦感染被消除，体重可以快速回升，但可能恢复不到其理想体重或病前体重。第二类病人则是缓慢的持续的体重减轻，这类病人常常有胃肠道症状并总是处于半饥饿状态。对于第二类患者，营养治疗的效果决定于在提供足够能量的同时减少胃肠道症状。以上两类情况均可造成明显的体重减轻，虽然发病机理不同，但在一个病人身上可以同时出现。另外评估HIV感染和营养状况的多个研究也显示出其临床表现的多样性。

The wasting seen in HIV infected individuals is multifactorial and heterogeneous (25, 30, 55, 61). Decreased dietary intake, gastrointestinal malabsorption and abnormal metabolism of nutrients are seen to varying degrees of severity, independently or in combination and are summarized in Table 2. HIV associated comorbid conditions emphasize the state of compromised health and vulnerability in patients. Patients may have multiple independent, but related complications (such as mouth sores, nausea, fever, diarrhea, fatigue) that pose a high degree of nutritional risk in this population. The diverse clinical spectrum of the disease and its effects on nutritional status underscore the need for individualized medical nutrition therapy for wasting. It is crucial to identify the mechanism of weight loss associated with each patient so that treatment may be appropriately targeted.

　　HIV感染者的消耗是多因素作用的结果(25, 30, 55, 61)。进食减少、胃肠道吸收障碍以及营养物质代谢异常的问题可以单独出现也可以合并出现，加上程度的不同导致了个体间的差异（表2）。HIV造成了患者免疫的缺陷增加了他們对多种疾病的易感性。因此，病人可能出现多种独立存在但同时又相互联系的并发症（如口腔疼痛、恶心、发热、腹泻、乏力），这些都会加重营养不良。针对消瘦的治疗需要个体化，针对其导致体重减轻的病因进行治疗。

Decreased dietary intake has been documented in all stages of HIV infection and may be secondary to anorexia, mouth sores, pain with swallowing, nausea, abdominal pain, vomiting, diarrhea, medication side effects, depression, dementia or fatigue (3, 41).

　　进食减少可以出现在HIV感染的任何阶段，這可能由多种因素导致，比如食欲下降、口腔疼痛、吞咽痛、恶心、腹痛、呕吐、腹泻、药物副作用、抑郁、痴呆或乏力等(3, 41)。

It has been theorized that high levels of cytokines circulating in HIV may be associated with anorexia but many medications that patients with HIV take may also cause anorexia or nausea. Studies attempting to quanitate calorie intake in HIV infected individuals show a wide range of intakes consistent with a heterogeneous disease (3, 5, 41). The most negative effects, or lowest dietary intakes, being seen in patients with AIDS or more advanced disease.

　　HIV感染者血循环中高水平的细胞因子 (cytokines) 可能与厌食有关，但许多药物也可能是导致厌食恶心的重要原因。定量分析研究显示HIV感染者热量摄入情况随疾病的进展而有很大不同(3, 5, 41)。进食最少的情况通常出现在AIDS或更晚期的患者身上。

Studies evaluating diet in otherwise healthy populations have documented marginal nutrient intakes in underprivileged segments of the population and this is likely to be true in HIV infected individuals as well. Access to adequate and appropriate nutrition may be an issue. Thus, the patients’ socioeconomic situation needs consideration in the overall risk assessment and treatment formulation. Use of alcohol or drugs may also negatively impact nutrient intake and dietary quality. As with many chronic diseases, when the patient becomes more debilitated, the ability to perform activities of daily living such as food shopping and preparation may be effected. Patients may also experience financial difficulties in the ability to obtain food. In some instances patients may be eating inappropriately because of lack of knowledge of appropriate nutritional intake.

　　与贫困地区的健康人群营养摄入减少相似，HIV人群可能存在同样的问题。他们所能获取的营养在质和量上可能都存在不足的问题。因此，在危险评价和治疗中需要考虑社会经济条件。饮酒和吸毒会对营养和进食质量有不良的影响。如同其他慢性疾病，随着患者变得衰弱，诸如购买食物，烹饪食物等日常活动都会受到影响；另外，患者还可能由于经济上的困难，无力购买食物、或因缺乏知识而不知如何安排適當的饮食。

The micronutrient status of HIV positive individuals has been evaluated in several studies and intakes close to the RDA reported for most nutrients, despite inadequate serum levels in many instances (4). However, many of these studies were done pre-HAART and may not apply in the current era, when patients are much more likely to be on effective suppressive antiviral therapy. This topic has been recently reviewed and many questions remain about the role of micronutrients in HIV infection and treatment in the era of HAART (64). Serum levels of many nutrients are difficult to interpret in inflammation; this concept will be discussed in greater detail under nutritional assessment. A progressive decline in serum micronutrient status has been associated with disease progression, and increased oxidative stress reported in HIV has been suggested as a potential cause of increased antioxidant requirements (2,4,15). Studies to date do indicate a correlation between dietary intake and serum levels of many nutrients, and HIV infected individuals probably have increased micronutrient needs, although the exact requirements for individual nutrients has not been determined (74).

　　研究提示，HIV感染者微量元素的摄入接近每日的标准推荐量，血清微量元素水平为正常低限(4)。这些研究中，大多数是在HAART治疗出现之前完成的，未必适用于现今的狀况。但微量元素在HIV感染者及治疗中的作用至今仍有争议(64)。在炎症的状态下，微量元素的水平很难评价，这些将在下面的部分中说明。血清中微量元素水平进行性降低可能与疾病进展相关，而HIV患者中氧化产物的增加可能导致了对抗氧化物摄入的需求增多(2,4,15)。因此，HIV患可能对微量元素有更高的需求。目前每种微量元素的标准需要量尚未确定，但已经有研究表明增加摄入有利于提高血清的微量元素水平(74)。

Malabsorption of nutrients may be secondary to intestinal infection with enteric pathogens, enteropathy, chronic antibiotic use or the effects of HIV on the intestinal epithelial cell (5, 28). Malabsorption as assessed by intestinal biopsies documented villous atrophy in sixty two percent of HIV infected individuals studied. Malabsorption has been reported in all stages of the disorder, and while malabsorption is common in diarrhea, studies have documented abnormal d-xylose tests and fat malabsorption in the absence of diarrhea (7, 31). In addition, there is still the strong suggestion that HIV enteropathy continues to occur. The gut is the largest lymphoid organ in the body and the persistence of virus in this reservoir may have a direct or indirect (via cytokine dysregulation) impact on gut function. Diarrheal illness can be acute or chronic in individuals with HIV and occurs in an estimated 20-50% of infected individuals in the pre-HAART era (71). Currently diarrhea in HIV infection is more likely to be associated with medications than with opportunistic pathogens. Studies have found a low calorie intake and high stool frequency, but not malabsorption, predictive of the severity of weight loss. Determination of the underlying intestinal defects is essential in defining appropriate nutrition therapy for the patient (68).

　　消化系统感染、肠病、长期抗生素使用或者HIV对于肠道上皮细胞的损伤都可能导致营养吸收不良(5, 28)。病理研究发现62%的HIV感染者有观察微绒毛萎缩，提示吸收不良。吸收不良可以发生在疾病任何阶段，常常与腹泻共存，但在没有出现腹泻的情况下，实验室检查也可发现D－木糖吸收试验异常和脂肪吸收不良(7, 31)。另外，HIV相关肠病一直存在。肠道是人体最大的一个淋巴器官，寄生HIV病毒（导致细胞因子调节紊乱）会对肠道产生直接或间接的影响。在HAART治疗出现之前，20-50%HIV感染者会出现急性或慢性的腹泻(71)。目前，药物导致的腹泻比机会性感染导致的腹泻更常见。研究发现低热量摄入、频繁腹泻都是体重减轻程度的预测指标。临床上，明确的诊断肠道本身的缺陷对于提供合适的营养補給治疗是必要的(68)。

Abnormal nutrient metabolism has been documented at varying stages of the disease and may be the result of multiple mechanisms including secondary infections or the cytokine mediated acute phase response to HIV infection (43). Altered assimilation of nutrients secondary to HIV infection or as a result of the medications used to decrease viral replication is also being evaluated and their role in the metabolic profile seen in some patients is under investigation. Resting Energy Expenditure (REE) has been evaluated in multiple studies of HIV infected individuals, including those with wasting. Reports have been inconsistent, finding both hypo and hypermetabolism (22, 34, 42, 56). One study reported normal Total Energy Expenditure (TEE) despite an increase in REE and theorized this was secondary to a decrease in physical activity (39).

　　HIV感染的不同阶段都会出现营养代谢异常，这可能与继发感染、细胞因子介导的急性期反应等机制相关(43)。HIV感染本身和药物对患者的吸收同化及代谢过程的影响正在研究当中。关于HIV感染者的静息能量消耗（REE，Resting Energy Expenditure）的研究结果不尽相同，高代谢状态和低代谢状态均有报道(22, 34, 42, 56)。有研究指出尽管患者静息能量消耗增多但总的能量消耗并没有改变，认为这可能是其活动减少的结果(39)。

The two primary patterns of HIV associated malnutrition of acute versus chronic weight loss previously described are thought to be due to distinctly different mechanisms (24). Determination of which primary mechanism has lead to wasting may aid in developing more appropriate therapy. It should be noted that because of the complexity of the disorder, these groups are not mutually exclusive nor are they the only causes of wasting.

　　前面提到的急性和慢性体重下降基于两种不同的机制(24)。对其进行鉴别对治疗至关重要。但值得强调的是这两种机制并不完全排斥，他们可能并存于同一患者中。

As discussed, patients with primarily gastrointestinal infections most frequently report a slow steady weight loss. These patients appear to have a normal metabolic response to malnutrition, including decreased basal metabolic rate. The primary underlying mechanism is inadequate dietary intake. The effects of starvation on otherwise healthy individuals have been well studied and are outlined in Table 3. Briefly, in the early stages (first 3-4 days), protein breakdown occurs as needed for gluconeogenesis. If the semistarvation state continues, long term adaptation of metabolism converts to reliance on fat as a primary fuel source, yielding ketones and sparing protein as much as possible. Basal metabolic rate decreases about 10% in an attempt to conserve energy; in children calories are shunted away from growth and toward body homeostasis. Therapy in these patients should be directed at providing adequate nutrients within the limitations of gastrointestinal function and repletion of body weight and lean body mass.

　　胃肠道感染的病人通常出现慢性持续性体重减轻。这些病人对营养不良反应出其正常的代谢反应，如基础代谢率降低等。其根本原因是进食不足，在表3中列出了饥饿对于正常人的影响。通常，在进食不足的前3-4天会有一些蛋白被降解以进行糖异生。如果这种半饥饿状态继续存在，躯体的代谢将出现一个适应性转变，即利用脂肪作为主要的能源，产生酮体，而尽量减少蛋白质的分解；同时，基础代谢率会降低10%左右以保存能量；在儿童，则以生长发育停滞来减少能量消耗。因此，针对这种情况的治疗主要包括在胃肠道功能允许的范围内提供足够的营养来恢复体重。

It is thought that in patients with acute weight loss secondary to non-gastrointestinal infections the underlying mechanism is a cytokine driven increase in energy expenditure and preferential catabolism of lean body mass, thus both calorie and protein needs are significantly elevated in these patients. Most studies document an increase in BMR of 10% or greater. The majority of studies have found fat free mass to be the best predictor of REE. Although patients demonstrate accelerated protein synthesis, particularly of acute phase proteins, protein breakdown is even more significantly elevated. Other effects on intermediary metabolism include alterations in carbohydrate and lipid metabolism with elevated serum triglycerides. These alterations in substrate utilization are thought to be responsible for the less than optimal response many patients have to refeeding, which includes significant gains in fat stores but limited deposition of lean body mass.

　　非胃肠道部位的感染所导致的急性体重减轻通常是缘于细胞因子介导的能量消耗增加，去脂肪体重的分解代谢加剧为主。病人对热量和蛋白的需求都大大提高了。多项研究都提示这种情况下基础代谢率可以提高10%以上。尽管部分的蛋白合成增加，如急性期蛋白等，但整体上机体蛋白成分的分解明显加快。糖类和脂肪的代谢也会有所变化，血清甘油三酯水平可以增高。由于这些代谢的改变，患者对补充营养的疗效较差，往往出现脂肪沉积增多而去脂肪体重并没有显著改变。

The overall goals of nutritional assessment are identification of patients at risk of nutrition deficiency or excess, design of individualized nutrition therapy, and the evaluation of nutrition interventions on health, complications, quality of life and survival. Because the areas of nutrition assessment each evaluate different aspects of nutritional status and can be relatively insensitive, evaluation of the patient is based on a combination of dietary, biochemical, clinical and anthropometric or body composition methods. Nutrition information must be integrated with the information from the medical history and physical examination (73).

　　进行营养状态评估的目标在于了解患者发生营养缺乏或过剩的风险、设计个体化营养治疗方案以及评估营养干预对于健康、并发症、生活质量和其存活的影响。由于每一项营养评估仅代表某一方面的营养状态，所以需要综合饮食、生化、临床和人体测量和机体组成等多方面的资料。同时其营养資料要结合病史和体格检查的结果(73)。

Dietary assessment is essential in evaluating current intake and determining barriers to adequacy. A number of methods exist for evaluating dietary intake; all have advantages and disadvantages and many clinicians use a combination of methods (24-hour recall followed by food records) to more accurately determine intake (38). The 24-hour recall asks the patient to describe all the food and beverages a person has consumed in the previous day or 24 hours. Information is obtained by interviewing the subject and/or family member about the type of food, amount, time and place where food is eaten. It requires about 20 minutes and literacy is not required. However, in an ill population food intake in the 24 hours prior to an interview may not be typical and recall skills vary. Food records require that the subject record all beverages and food consumed over a specific period of time, usually 1 to 7 days, including one weekend day. Subjects must be literate and cooperative, but recall is not a bias and the information obtained is detailed. The diet history method attempts to establish usual intake of a person over several months to a year. Detailed background information relevant to diet such as income, allergies etc., is obtained along with a 24-hour recall and food frequency information. While it provides a more complete and detailed intake and accounts for variation, it is time consuming, dependent on memory and requires a highly skilled interviewer. All of these methods have the problem of accuracy in patient reporting and errors in nutrient analysis, but are recommended for use in clinical practice in the assessment of individual intakes. From the information obtained the clinician can formulate an intervention that is individualized to optimize the patient's nutritional status.

　　饮食评估对明确目前的饮食情况和摄入不足的原因都是必需的。饮食评估的方法很多，各有优缺点，不少临床医生倾向于综合运用各种方法（比如回忆24小时内进食同时结合做食物日记等）来更精确地了解每日食物摄入量(38)。24小时回忆法是让病人描述前一天或24小时内所有摄入的食物饮料，可以通过询问本人和/或其家人食物的类型、数量、时间、地点等等来获取信息，大致需要20分钟，被询问者可以不识字。但是，某一天的食物可能不具有代表性，而且可能存在回忆偏差。食物日记法需要参与者在一定的时间（通常1-7天，包括一个非工作日）内每天记录所有的进食。参与者需要有读写能力，能与医生配合，能详细记录所有信息。食物日记一般需要记录几个月到一年的时间。与食物相关的其他信息，如收入，过敏等一般是在使用24小时回忆法和了解饮食频率时同时采集。详细的饮食调查需要时间和耐心，同时有赖于患者的记忆力和医生的调查技巧。没有某种方法是完美的，因此通常需要结合使用。根据这些信息，医生们可以有针对性地设计适合病人的营养方案。

The importance of changes in body composition in HIV infected individuals has been discussed and increasingly sophisticated methods of assessment are being developed. A general overview of methods available, basic assumptions, technical difficulty, accuracy and cost are summarized in the following references (38, 48). Many methods are used exclusively for research. Most assume normal body water distribution, use various equations to determine body compartments (generally fat free and fat mass) and not all have been validated in subjects with HIV infection. Anthropometry is the assessment of body size and its’ proportions by measuring limb circumferences and skin fold thickness at various locations. In general it is a very good indicator of overall nutritional status and should be routinely assessed in any population with a chronic disease. Although simple, inexpensive, and accurate in many populations, it is an indirect measure of body fat and lean body mass and has the disadvantages of not separating out fluid shifts between body compartments. Weight, height, skinfold thicknesses, and arm circumference are the primary measures. Waist and hip circumference are also useful in following fat redistribution. Weight is expressed as percent ideal body weight, percent usual body weight, and body mass index in weight in kg/ height in m². Although weight alone may not be sensitive, pattern of weight loss is important to evaluate and routinely graphing weight data is useful in following nutritional status over time. Bioelectrical impedance though practical, may not be accurate in people with regional changes in fat. Dual Energy X-ray Absorptiometry (DEXA), while accurate, is currently less available and relatively expensive except in research settings for assessment of body composition.

　　HIV感染者机体组成的变化是营养评估中一个很重要的方面，相关的评估方法也逐渐增多。参考文献中的部分文章对这些方法做了详细的总结归纳(38, 48)。其中许多方法目前仅用于研究。大多数方法是基于固定的机体水成分这一假设，然后用各种不同的公式去计算机体组成（如去脂肪体重和脂肪量）。并不是所有方法都在HIV感染者中进行了验证。身体测量法是通过测定臂围、不同部位的皮褶厚度来评估体型和各成分组成的。通常而言，这是一种评估全身营养状况的很好方法，可以作为慢性病人群的常规评估项目。尽管简单、廉价、并在大多数人群中有很高的精确性，它只能间接估计脂肪和去脂肪体重，同时不能反应在不同身体部分水分组成。体重、身高、皮褶厚度和臂围是最主要的指标，在估算体脂分布时，腰围、臀围也很重要。体重可以被表示为理想体重的百分之几，常人体重的百分之几，体重指数（BMI）等。尽管单独一项体重可能并不敏感，但体重减轻的类型以及常规记录的体重数据对于长期评估营养状况是很有意义的。生物阻抗法虽然实用，但在脂肪异常分布的人群中结果的准确性受到一定影响。双能X线吸收测量法（DEXA，Dual Energy X-ray Absorptiometry）比较精确，但目前应用不十分广泛并且相对成本较高。

Laboratory or biochemical assessment of nutritional status generally measures a nutrient or its metabolite in blood, urine or feces and is frequently used to confirm deficiencies or excesses suspected on dietary clinical, or anthopometric evaluation (38). Biochemical measurements usually detect changes before clinical or anthropometric measures of assessment and provide objective data on nutritional status. Laboratory evaluation of protein status, a metabolic profile for lipid and carbohydrate utilization and primary micronutrients of issue in HIV infected individuals should be assessed on routine nutrition screening (see Table 4). A more in-depth biochemical assessment will depend on the clinical risk factors of the individual patient, any abnormalities determined on screening, and may include more sensitive measures of protein status, metabolism and micronutrient status. Micronutrient status of HIV infected individuals is particularly difficult to assess by standard laboratory tests as patients have depressed serum levels of many micronutrients secondary to inflammatory mediator shifts and are not truly deficiency. Assessment of enzymes or functional parameters dependent on the specific nutrient may be a more valid measure of nutritional status in these cases.

　　实验室或生化检查通常是用血液、尿液、或粪便为样本，测定其中一种营养素或者代谢产物，来明确临床或身体测量得到的营养缺乏或过剩的初步诊断(38)。生化检查通常比临床或身体测量能更早地发现异常，并且提供营养状态相关的客观数据。对于HIV感染者，实验室测定蛋白水平以及血脂水平等应该作为营养评估的常规（见表4）。是否需要更复杂的生化检查，比如用更敏感的方法测定蛋白水平、代谢以及微量元素水平，取决于病人的个体情况和初步筛查的结果。对于HIV感染者，常规的实验检查测定的微量元素水平可能不能反映出实际情况，因为炎性介质的作用可以使某些微量元素水平降低。在这种情况下，检查特定的酶活性或某些功能指标是更准确的方法。

Subjective global assessment (SGA) of nutritional status has also been effectively applied in HIV infected subjects showing good correlation with body composition and deteriorating nutritional status. SGA also correlated well with the CDC case definition of wasting and identified malnourished patients but did not detect early wasting (48).

　　营养状态个人综合评估法（SGA，Subjective Global Assessment）已经被有效地运用于HIV感染者，与机体组成和营养状态的恶化等呈明显的相关性。该方法也与CDC定义的消瘦以及营养不良有很好的相关性，但不能用于发现早期的消瘦。

Prevention of wasting/weight loss by frequent weight monitoring and risk assessment with education on nutrition and exercise goals is essential. Similarily, assessment of comorbidities and treatment side effects which may impact weight loss is important. Treatment of associated infections and achieving optimal HAART therapy is a primary medical goal in conjunction with appropriate medical nutrition therapy. Assessment of level of risk for wasting reflects consideration of the complex factors discussed above which may lend to nutritional compromise.

　　为了预防体重减轻和消瘦，患者需要进行定期体重监测、风险评估并接受关于营养和运动的教育。同时，医生要及早诊断各种并发症，并相应调整影响体重的治疗方案。营养治疗最主要的目的在于协助治疗HIV相关感染，达到HAART治疗的最佳效果。消瘦的风险评估事实上就是对上诉可能导致营养状况不佳的各种因素加以综合考虑。

Medical nutrition therapy aims to prevent and/or treat HIV associated nutrition complications (1). In HIV related wasting, the primary goal is an increase in lean body mass proportion of weight gain and as previously discussed; devising effective treatment strategies depends on understanding the underlying causes of wasting in each patient (46, 47, 50). Energy and protein needs should be estimated, with additional calorie sources broadly following the Dietary Guidelines. Micronutrient supplementation may be required during treatment of wasting, as intake may have been inadequate for some time.

　　临床营养治疗目的在于防止和/或治疗HIV相关的营养并发症(1)。对于消瘦的患者，营养治疗的主要目标在于增加去脂肪体重。如前所诉，每个病人消瘦原因不同导致了治疗策略各异(46, 47, 50)。原则上，营养治疗应按照饮食指南（Dietary Guidelines）估算能量和蛋白的需要量，选择合适的热量来源。由于很多病人会出现摄入不足，有时也需要补充微量元素。

How to best achieve optimal nutrient intake is then determined. This is best achieved in conjunction with a registered dietitian experienced with HIV. If it is possible for the patient to meet caloric goals through a regular diet, nutrition counseling should focus on how to best achieve this. Oral supplements help many patients whose intake is difficult to increase, and should be the first step in nutrition support of the patient. Enteral or parenteral nutrition support are important therapies but are less physiologic, more invasive and costly and should be used appropriately as determined by either gastrointestinal limitations or other medical indication (32). Goals should be set for restoration of a healthy, lean body mass and micronutrient repletion. Nutrition recommendations should be modified, as needed based on follow up assessment of nutritional status.

　　接下来是设定合理的营养摄入目标。如有条件，建议有治疗HIV感染者经验的营养师参与。如果患者可以通过正常的进食摄入足够的热量，那么主要的问题就在于如何最好地达到这个目标。而那些日常饮食又难以达标的患者，口服营养添加剂是首选。肠内或肠外营养支持不是生理过程，价格贵，并且是有创的，因而适用于无法口服的患者(32)。营养方案应以恢复正常的去脂肪体重和正常微量元素水平为目标；执行过程中，应随着营养评估结果而调整。

Exercise has also been shown to improve body composition and may also stimulate appetite. More specifically, progressive resistance exercise training (PRT) has been associated with increased weight and lean body mass in HIV associated wasting and in conjunction with individualized nutrition counseling (57).

　　锻炼同样可以改善机体组成并增进食欲。特别是长期耐力训练（PRT）结合个体化的营养治疗都有助于恢复体重，增加去脂肪体重，纠正HIV导致的消瘦(57)。

While consultation with a dietitian or nutritionist is the cornerstone of therapy for wasting and weight loss there are situations in which pharmacological interventions for these conditions will be of great benefit to patients (9).

　　营养师的指导对于治疗体重减轻很有帮助，但某些情况下，药物干预对病人也是必要的(9)。

For patients who have anorexia, treatment with an appetite stimulant can result in a significant increase in nutrient intake. Both megestrol acetate and dronabinol have been shown to increase caloric intake (63, 66). The composition of accrued weight with megestrol acetetate has been determined; the majority of the increase in body weight is fat mass (2/3 fat and 1/3 lean) (66). The majority of side effects with megestrol acetate are related to its hormonal characteristics; it may lead to menstrual irregularities in women and sexual dysfunction in men; it may also lead to fluid accumulation and has been associated with venous thrombosis and adrenal suppression (12). The side effects of dronabinol are more limited; the most common side effect is a dysphoria which can be debilitating in some patients.

　　对于厌食的病人，使用食欲促进剂可以明显提高营养摄入，如醋酸甲地孕酮（megestrol acetate）和屈大麻酚（dronabinol）(63, 66)。醋酸甲地孕酮导致的体重增加大部分是脂肪的增加（2/3脂肪，1/3去脂肪体重）(66)。它的副作用主要与其激素特性有关，可能会导致妇女月经紊乱、男性性功能障碍，另外还可能导致液体潴留、静脉血栓形成以及肾上腺抑制等(12)。而屈大麻酚的副作用相对少，最常见的副作用是烦躁不安，在有些病人中可能表現得很严重。

For patients who have suffered a loss in lean body mass but have adequate nutrient intake the use of anabolic agents may be considered. Anabolic agents may be androgens (testosterone) or androgenic analogues (nandrolone, oxandrolone, oxymethalone) or more purely anabolic (growth hormone) (6, 13, 18, 20, 27, 37, 44, 45, 54, 59, 60). All of these agents have been shown to be effective in increasing lean body mass, although the amount of increase has not returned lean body mass in most patients to their pre-morbid weight or body composition. Evidence is accruing that combination therapy (appetite stimulant plus androgenic agent and/or exercise) may be superior to single agent therapy in treating HIV associated weight loss and wasting (53, 67). Each of the anabolic agents has a distinctive side effect profile and each has a different route of administration. Testosterone may given by injection, by transdermal patch or in a gel formulation; nandrolone is an injection and both oxandrolone and oxymethalone are oral agents. All have been shown to be safe and effective in women as well as men. Growth hormone was able to promote a substantial increase in lean body mass in patients with HIV and is the only agent to result in an increase in lean mass and a commensurate decrease in fat mass. However, growth hormone is also an injection and has a side effect profile that includes arthralgias, myalgias, fluid retention and rarely, the development of hyperglycemia. It must be noted that intensive progressive resistance training has been able to result in equal increases in lean body mass as growth hormone and for the patients who are able to adhere to a rigorous exercise program, avoids all of the potential side effects of the pharmacologic interventions (14, 52).

　　针对进食正常但去脂肪体重减轻十分明显的患者，可以考虑使用促进合成代谢的激素类药物，比如雄激素（睾酮）、雄激素类似物（辛烯酸诺龙，氧甲氢龙）或直接促进合成代谢的药物（生长激素）(6, 13, 18, 20, 27, 37, 44, 45, 54, 59, 60)。虽然不能使患者恢复到病前状态，所有的这些药物都能有效地增加去脂肪体重。越来越多的研究表明对于HIV相关的体重减轻和消耗，联合治疗（食欲促进剂合用雄激素类似物和/或锻炼）比单独用一种方法治疗效果好(53, 67)。每种促进合成代谢的药物都有各自的副作用和不同的使用方法：睾酮可以通过注射、透皮贴剂或凝胶；辛烯酸诺龙是注射用药而氧甲氢龙则是口服用药。这些药物在女性和男性中使用一样安全有效。生长激素可以使HIV感染者去脂肪体重明显增加，并且是唯一一种能导致去脂肪体重增加、同时脂肪减少的药物。它是一种注射用药，可能带来关节疼痛、肌肉疼痛、水液潴留，以及较少见的高血糖等多种副作用。坚持积极的耐力训练能达到和使用生长激素一样的增加去脂肪体重的效果，同时避免了药物的副作用(14, 52)。可惜人们对于运动的重要性还认识不足。

Attempts to revert cytokine status to normal by blocking TNF with pentoxyfylline have not been successful in treating HIV weight loss (10). The precise mechanism by which thalidomide works is not clear, but thalidomide has been successful in increasing lean body mass in patients infected with HIV (29, 51). The side effect profile of thalidomide has limited its usefulness, as up to 50% of patients in some trials have requested that the drug be discontinued.

　　其他药物的研究显示，通过pentoxyfylline阻断肿瘤坏死因子 (TNF，tumor necrosis factor)以纠正细胞因子紊乱来治疗体重减轻的尝试并不成功(10)。反应停可以改善HIV导致的体重减轻，但确切机理尚不明确(29, 51)。而且，反应停的副作用限制了它的使用，在某些试验中甚至有超过50%的病人要求停止该药。

The use of highly active antiretroviral therapy has significantly reduced the morbidity and mortality associated with HIV; at the present time it is feasible to consider HIV as a chronic manageable disease. However, wasting and weight loss remain common and are associated with increased mortality. Attention must be paid to the nutritional status and needs of HIV infected patients to allow quality of life to be maximized for these patients.

　　HAART治疗改善了HIV的预后，使其成为了一种可以控制的慢性病。但HIV导致的体重减轻和消耗仍很常见，并且与患者的预后相关。HIV病人的营养状况及需求是一个值得关注的问题，合理解决这一问题可以使患者的生活质量得到最大的改善。

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