Complementary and Alternative Therapies to Manage HIV-Related Symptoms

Continuing Education Offering

Complementary and Alternative Therapies to Manage HIV-Related Symptoms Barbara Swanson, DNSc, RN, ACRN Joyce K. Keithley, DNSc, RN, FAAN Janice M. Zeller, PhD, RN, FAAN Diane Cronin-Stubbs, PhD, RN, FAAN Persons with HIV infection report substantial use of complementary and alternative medical (CAM) therapies for symptom management. Anecdotal reports from patients indicate that CAM approaches are helpful; however, there is limited scientific information on the safety and efficacy of these therapies in the HIV population. The purpose of this review is to critically appraise the scientific evidence for selected CAM therapies that are used by HIV-infected persons to manage three common symptoms: nutritional alterations, pain, and depression. Key words: HIV, complementary therapies, pain, nutritional alterations, depression

Throughout history, there have been periods when the American public has expressed interest in utilizing “medically unproven” complementary and alternative medical (CAM) practices for curing disease or treating unrelenting symptoms (Jonas, 1998). Although this interest has waxed and waned over the years, it has recently been voiced in a prominent medical journal that the use of CAM practices by Americans is here to stay (Jonas, 1998). A groundbreaking study by Eisenberg and his colleagues revealed that in 1990, over 30% of Americans sought treatment from alternative health care practitioners and made more visits to these practitioners than to conventional medical providers (Eisenberg et al., 1993). Recently, this group reported that visits to CAM practitioners by Americans have increased significantly since publication of the original report (Eisenberg et al., 1998). There is

growing interest by conventional health care providers to discuss CAM practices with their patients in an informed manner; however, the lack of controlled, empirical data to evaluate the efficacy of CAM practices has limited these activities. In an attempt to gain further information regarding the safety and efficacy of such practices, the National Center for Complementary and Alternative Medicine was established by Congress in 1998. Under the auspices of this center, significant funds have been awarded to support investigator-initiated research projects, and centers in CAM research have been established to set directions for future research in this area. Reports indicate that persons who seek care from alternative health care providers are most often those who suffer from chronic illnesses or other conditions that are either refractory to or only partially ameliorated by conventional medical treatments (Eisenberg et al., 1993; Eisenberg et al., 1998). Although many persons who use CAM treatments use them at the expense of conventional medical approaches, more commonly they are used in conjunction with conventional therapies. Recent reports note that HIV-infected persons are frequent users of CAM therapies, which include the use of herbal and dietary supplements and visits to CAM practitioners (Fairfield, Eisenberg, Davis, Libman, & Phillips, 1998). Earlier in the HIV/AIDS epidemic, infected persons primarily utilized CAM the ra pie s tha t w e re purporte d to have immunostimulatory or antiviral properties (Elion & Cohen, 1997). Since the introduction of highly active

JOURNAL OF THE ASSOCIATION OF NURSES IN AIDS CARE, Vol. 11, No. 5, September/October 2000, 40-60 Copyright © 2000 Association of Nurses in AIDS Care

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antiretroviral therapy (HAART), CAM therapies have been more frequently utilized to manage the untoward side effects of antiretroviral medications (MacIntyre & Holzemer, 1997). The opportunity to manage certain symptoms of HIV disease may not only improve patient well-being but may additionally influence immune status integrity in this population. Preliminary data exist in the literature to support the use of CAM therapies to alleviate clinical symptoms in persons with HIV disease. These therapies include herbal remedies and nutritional supplements (Coss, McGrath, & Caggiano, 1998; Tyler, 1993), and physical approaches, such as acupuncture (Galantino, Eke-Okoro, Findley, & Condoluci, 1999) and massage therapy (Ironson et al., 1996). We have chosen to address three symptoms in HIV-infected persons in this review on CAM: nutritional alterations, pain, and depression. This decision was based on their prevalence in the HIV population and potential for CAM utility in the treatment of these symptoms. Although nutritional alterations, pain, and depression may be individually observed in HIV-infected persons, there is evidence that these clinical problems are closely interrelated. For example, persons experiencing pain as a primary symptom frequently report loss of appetite (Ferrell & Ferrell, 1995; Grond, Zech, Diefenbach, & Bischoff, 1994) and may become depressed if pain relief is not achieved (McDaniel, Musselman, Porter, Reed, & Nemeroff, 1995). When caring for persons with HIV disease, clinicians need to be cognizant of potential interactive effects of nutritional alterations, pain, and depression when evaluating responses to therapy.

Lipodystrophy, or Fat Redistribution, Syndrome Nutritional alterations are pervasive throughout the course of HIV infection. The most commonly reported nutritional alterations are vitamin and mineral deficiencies, wasting, and the emerging lipodystrophy syndrome (Baum & Shor-Posner, 1998; Carr, Samaras, Burton, et al., 1998; Wheeler et al., 1998). This section will focus on the pathogenesis and alternative management of dyslipidemia, a component of lipodystrophy syndrome (LD). Affecting quality of

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life and survival, LD is a serious complication of HIV/AIDS (Eastone & Decker, 1997; Henry et al., 1998). LD is a term that is widely used to describe the changes in fat distribution and metabolism that many patients with HIV/AIDS are experiencing (Behrens et al., 1999; Carr, Samaras, Burton, et al., 1998; Dieterich et al., 1999; Lo, Mulligan, Tai, Algren, & Schambelan, 1998; Miller et al., 1998; Saint-Marc, Poizot-Martin, Partisani, Fabre, & Touraine, 1999; Viraben & Aquilina, 1998). The syndrome is characterized by fat loss from the face, arms, legs, and buttocks, in conjunction with marked fat gain in the dorsocervical region, abdomen, and breasts (in women). Other characteristics of the syndrome include insulin resistance, hyperglycemia, and dyslipidemia. HIV-related dyslipidemia is characterized by elevations in serum triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoproteins (VLDL), and/or a reduction in high-density lipoprotein (HDL) cholesterol. Serum lipid elevations occur at levels above which diet and drug therapy should be initiated (National Cholesterol Education Program, 1993). The reported prevalence of LD broadly ranges from 5% to 64% in men and 7% to 18% in women (Carr, Samaras, Burton, et al., 1998; Dieterich et al., 1999; Gharakhanian et al., 1999). Variations in reported prevalence are probably due to the lack of precise diagnostic criteria and the confounding effects of variable antiretroviral and anabolic regimens in the patient cohorts studied. The mechanisms underlying LD are unclear. One hypothesis is that LD may be directly related to protease inhibitor (PI) therapy. Although metabolic abnormalities were observed before HAART was introduced (Grunfeld et al., 1989), HAART seems to be associated with an increase in these abnormalities (Carr, Samaras, Burton, et al., 1998). Carr, Samaras, Chisholm, and Cooper (1998) suggest that protease inhibitors might bind to a homologous human protein involved in lipid metabolism, potentially leading to alterations in serum lipid concentrations and apoptosis of peripheral adipocytes, with subsequent visceral fat accumulation. However, this hypothesis does not account for the occurrence of LD in PI-naive patients (Christeff et al., 1999; Saint-Marc et al., 1999).

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Another hypothesis is that nucleoside-analogue reverse-transcriptase inhibitors (NRTIs) cause mitochondrial toxicity, characterized by abnormal mitochondrial DNA and oxidative phosphorylation via cytochrome P450-3A, which may be linked to the pathogenesis of LD (Brinkman, Smeitink, Romijn, & Reiss, 1999). Another postulation is that LD may be a secondary consequence of chronic suppression of HIV replication, rather than a primary effect of protease inhibitor-containing regimens (Kotler, 1999). Because of similarities between LD and Cushing’s syndrome, cortisol levels have been postulated to play a role in the development of LD. Most studies have shown normal cortisol levels in patients with LD (Carr, Samaras, Chisholm, et al., 1998; Lo et al., 1998), with the exception of a recent study in which positive correlations between cortisol and LD were observed (Christeff et al., 1999). Others suggest that high fat diets in conjunction with HAART, the aging of the HIV/AIDS population, or the severity of HIV infection may be factors in LD (Carr, Samaras, Burton, et al., 1998; Kotler, 1999). It remains unclear whether LD is one or several different syndromes. A recent multicenter study by SaintMarc et al. (2000) suggests that LD should be subdivided into three distinct categories: (a) a fat atrophy or depletion syndrome, possibly related to the use of stavudine; (b) a fat redistribution syndrome, perhaps a by-product of effective virus control; and (c) an increase in subcutaneous fat, likely associated with increased calorie intake. The accuracy of these hypotheses and subcategories in explaining the underlying causes of LD has yet to be confirmed. Despite the lack of consensus regarding the prevalence and pathogenesis of LD, its influence on patient outcomes is of considerable concern. LD is not only associated with the premature development of cardiovascular disease and, possibly, diabetes mellitus but also with the distressing and disfiguring physical changes of fat redistribution (Eastone & Decker, 1997; Henry et al., 1998). These adverse outcomes are causing many patients to discontinue HAART, despite its efficacy in reducing viral burden, and to turn to alternative therapies (Kotler, 1999).

CAM Therapies and Dyslipidemia CAM therapies are widely used for HIV-associated nutritional alterations. A telephone survey of 180 patients with HIV infection found a high rate (68%) of dietary and herbal supplement use (Fairfield et al., 1998). The major reasons identified for using supplements were to treat weight loss and other nutritional alterations, and patients who used supplements for those reasons reported substantial benefit. These findings are consistent with the findings of Ostrow et al. (1997) who, in an extensive survey of HIV-infected persons (N = 657), found that 52% had used dietary supplements and herbal therapies. Due to the extensive array of available dietary supplements and herbal remedies, this discussion will focus on two alternative supplements—Cholestin and garlic—that show potential for managing HIV-related dyslipidemia. Cholestin Cholestin (Pharmanex, Inc., Simi Valley, CA) is a proprietary form of Monascus purpureus Went yeast fermented on rice, a traditional Chinese health food. The fermentation process yields statins, which are substances that lower lipid levels by inhibiting an enzyme necessary for cholesterol synthesis, HMGCoA reductase. Cholestin differs from the red yeast sold in Chinese groceries as a food colorant and flavor enhancer in that it contains higher amounts of statins. Cholestin is manufactured by growing a single strand of M. purpureus on rice under carefully controlled conditions that increase the statin content (U.S. Department of Health and Human Services, Food and Drug Administration, 1997). Each capsule of Cholestin contains 600 mg of scientifically standardized M. purpureus Went yeast fermented on premium rice, with naturally occurring HMG-CoA reductase inhibitors (0.4%), including mevinolin, as well as significant levels of unsaturated fatty acids. Yeast is inactive in the final product. The amount of statins in 2.4 g of Cholestin is approximately 10 mg, an amount found to reduce LDL cholesterol by 17% in patients with familial hypercholesterolemia (Havel et al., 1987).

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Cholestin is hypothesized to exert its lipid-lowering effects through the combined presence of HMG-CoA reductase inhibitors and high concentrations of unsaturated fatty acids, as well as natural compounds. Two recent clinical trials conducted in healthy populations in the United States have documented the efficacy and safety of Cholestin. In one study, Heber et al. (1999) examined the lipid-lowering effects of Cholestin in 83 men and women with elevated LDL cholesterol concentrations. After 12 weeks of supplementation, total cholesterol decreased significantly (p < .001) in subjects who were randomly assigned to receive Cholestin (2.4 g daily) compared with those assigned to the placebo group. Cholestin also reduced LDL cholesterol and triglycerides and did not significantly change HDL cholesterol. None of the study subjects reported any adverse effects. A second study that was a multicenter clinical trial conducted at 12 U.S. sites, evaluated Cholestin in 187 participants with mildly to moderately elevated levels of cholesterol (M = 242 mg/dl) (Rippe et al., 1999). Levels of total cholesterol were reduced by 16.4%, LDL cholesterol by 21.0%, and triglycerides by 24.5%, and levels of HDL cholesterol were increased by 14.6% in subjects treated with an 8-week course of Cholestin (2.4 g/day) when compared with the placebo group. Thirty-four subjects (18%) experienced adverse effects such as headache, abdominal bloating, and gas. To date, no prospective randomized trials of Cholestin have been conducted in patients with HIV-related dyslipidemia. Clinical Implications In clinical trials of Cholestin in the United States and abroad, the only adverse effect reported (in a small number of participants) was slight gastrointestinal discomfort and headache. No clinically significant changes in routine blood tests or renal or liver function tests were noted (Medical Economics, 1999). Additionally, in acute and long-term animal toxicity studies, there were no adverse reactions at doses up to 50 times the normal human dose over 3 to 4 months (Li et al., 1998; Medical Economics, 1999). Because statins are primarily metabolized through cytochrome 3A4, an isoform that is inhibited by all PIs, a potential concern is that they may have toxic effects when

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coadministered with HAART (Piscitelli, Flexner, Minor, Polis, & Masur, 1996). Until further data become available, patients should be monitored for changes in liver enzymes, CD4 counts, and viral RNA; myopathy; and any other signs or symptoms of untoward effects. Garlic Two meta-analyses of studies conducted in patients without HIV infection suggest that garlic treatment results in sustained reductions of total cholesterol by 9% to 15% (Silagy & Neil, 1994; Warshafsky, Kramer, & Sivak, 1993). Various garlic dosages were used, including 600-900 mg/day dried powder preparations; 10-20 g/day fresh, high allicin garlic; or 1 g/day aqueous extract. Following 1 to 3 months of therapy with the various dosages, patients demonstrated significant lowering in cholesterol levels, which persisted for as long as 6 months. Serum triglycerides also dropped significantly. In contrast, a few investigators have reported that garlic has no effect on lipid levels. Issacsohn et al. (1998) studied 28 patients who received 900 mg of garlic powder per day (equivalent to approximately 1 clove of fresh garlic per day) for 12 weeks. Compared with the placebo group of 22 patients, no significant lipid or lipoprotein changes were found in the garlic-treated group. These findings are consistent with those reported earlier by Simons and associates (1995). In a 12-week crossover study of 30 patients who received either 900 mg of garlic powder tablets per day or a matching placebo, no demonstrable effects of garlic ingestion were detected on lipid or lipoprotein levels. Therefore, the efficacy of garlic as a lipid-lowering agent remains controversial. Other related studies report that garlic administration increases fibrinolytic activity (DeSmet, 1997), decreases platelet aggregation, and has hypotensive effects (Neil et al., 1996). To date, no prospective randomized trials of garlic have been conducted in patients with HIV disease. Clinical Implications Garlic preparations are commercially available in several liquid and powder forms (e.g., distilled garlic oil capsules, oil-based garlic preparations, garlic aged

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in aqueous alcohol; deodorized garlic capsules; enteric coated tablets), as well as fresh bulbs and cloves. The concentration of the active ingredient in garlic, allicin, can vary considerably among garlic products and is inactivated by heat, crushing, or acidic environments (Murray & Pizzorno, 1998). The German Commission E recommends that products deliver the equivalent of 4,000 mg of fresh garlic, roughly 1 to 4 cloves (Blumenthal, Hall, & Rister, 1997). Adverse effects reported with garlic include heartburn, flatulence, gastrointestinal upset, allergic reactions, contact dermatitis (from exposure to garlic bulbs and juice), and skin and breath odor. Enteric coated tablets reduce offensive odors and dissolve in the more basic environment of the small intestine. Because garlic may reduce clotting time and blood pressure, persons taking aspirin or other anticoagulants and antihypertensives should avoid consuming large amounts of garlic. HIV-related dyslipidemia is associated with serious health risks, most notably the development of premature cardiovascular disease and the lack of adherence to HAART regimens. Because of its emerging nature and unknown pathogenesis, effective lipid-lowering interventions—either conventional or alternative—are only beginning to be tested for HIV-related dyslipidemia. Data in non-HIV-infected populations suggest that lipid-lowering agents such as Cholestin and garlic may be partially efficacious in normalizing serum lipid levels in HIV-related dyslipidemia. However, these findings need to be replicated in and/or extended to persons with HIV infection.

Pain Pain is a common symptom among persons with HIV/AIDS, with recent studies reporting prevalence rates ranging from 54% to 62% (Breitbart et al., 1997; Breitbart et al., 1996; Hewitt et al., 1997; Vogl et al., 1999). Pain may be related to complications of HIV infection (e.g., aphthous ulcers) or to the toxic effects of antiretroviral medications (e.g., nucleoside analog-induced peripheral neuropathy). Pain may also represent syndromes that are unrelated to HIV infection or its treatment and are common in the general

population (e.g., low back pain) (Breitbart & Patt, 1994). A substantial body of data indicates that pain is undertreated in persons with HIV/AIDS (Breitbart et al., 1997; Breitbart et al., 1996; Frich & Borgbjerg, 1996; LaRue, Fontaine, & Colleau, 1997). In two separate studies of AIDS patients who reported pain (N = 226 and 144), approximately 85% of participants in each study received inadequate pain medications according to the World Health Organization (1990) “analgesic ladder” system (Breitbart et al., 1996; LaRue et al., 1997). In one of the studies, only 15% of participants who reported that they were experiencing severe pain received opioids (LaRue et al., 1997). Barriers to adequate pain management have been identified for both patients and providers. Patientrelated barriers include fear of addiction, distressing side effects, belief that pain medications should be withheld until pain becomes severe, and a reluctance to acknowledge pain because it is perceived as a marker of disease severity (Breitbart et al., 1998). Provider-related barriers include self-reported lack of knowledge regarding pain management, reluctance to prescribe opioids, lack of access to pain specialists, and fear of addiction (Breitbart, Kaim, & Rosenfeld, 1999). Among the general population, complementary therapies are frequently used to manage pain. A national telephone survey of randomly selected households in 1997 revealed that neck and back problems were the two most frequently cited reasons for using complementary therapies within the previous year (Eisenberg et al., 1998). Although it seems likely that a substantial number of persons with HIV/AIDS also use complementary therapies to manage their pain, there is a paucity of data on the prevalence and patterns of CAM use specifically for pain by HIV-infected persons. One study of 256 persons with HIV/AIDS identified that self-reported pain was a significant predictor of CAM use (Ostrow et al., 1997). In a survey of the CAM practices of 180 HIV-infected communitydwelling persons, pain or neuropathy was the most frequently cited reason for seeing a CAM practitioner in the previous year (33.3% of reports) (Fairfield et al., 1998). In this section, the scientific literature will be reviewed on the analgesic mechanisms and efficacy of

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two CAM therapies for managing pain associated with HIV/AIDS: acupuncture and capsaicin. Acupuncture Acupuncture refers to a group of procedures, derived from traditional Chinese medicine (TCM), that involve stimulation of specific points on the body, usually through the insertion of fine needles (National Institutes of Health, 1997). According to the principles of TCM, the function of the human body is controlled by Qi, a vital force that circulates among organs through channels known as meridians. Illness is postulated to result from disruptions in the flow of Qi that can be normalized by inserting needles at key points along the meridians. The needles may be left in place, manually rotated, stimulated with electrical current, or heated with burning Artemesia vulgaris leaves (moxibustion) (Helms, 1998; Vickers & Zollman, 1999). Analgesic Mechanisms of Acupuncture Both animal and human studies have shown that stimulation of acupuncture points can elicit physiological responses that may mediate pain relief (Pan, Castro-Lopes, & Coimbra, 1996; Petti, Bangrazi, Liguori, Reale, & Ippoliti, 1998; Pintov, Lahat, Alstein, Vogel, & Barg, 1997; Sumiya & Kawakita, 1997). Acupuncture stimulates the release of endogenous opioids that have known analgesic effects (Pan et al., 1996; Petti et al., 1998; Pintov et al., 1997). Furthermore, these analgesic effects can be inhibited by injections of naloxone, an opioid receptor antagonist (Chen, Geller, & Adler, 1996). Acupuncture can also affect pathways in the central nervous system that are involved in pain perception. In magnetic resonance imaging studies of healthy human volunteers, stimulation of acupoints has been associated with activation of descending antinociceptive pathways (Wu et al., 1999) and deactivation of limbic structures, which are thought to be involved in cognitive-affective aspects of pain perception (Hui et al., 2000; Wu et al., 1999). Research on Analgesic Effects of Acupuncture Randomized clinical trials of acupuncture to manage pain have yielded contradictory findings. Some

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studies and meta-analyses have identified that stimulation of true acupuncture points is more effective than sham or placebo acupuncture in relieving pain related to fibromyalgia (Deluze, Bosia, Zirbs, Chantraine, & Vischer, 1992), postoperative dental pain (Lao, Bergman, Hamilton, Langenberg, & Berman, 1999), chronic myofascial neck pain (Birch & Jamison, 1998), back pain (Ernst & White, 1998), and rotator cuff tendinitis (Kleinhenz et al., 1999). In contrast, other studies and “best evidence syntheses” have found that true acupuncture is no more effective in relieving pain than either sham or placebo procedures or no treatment (Gupta, Francis, Tillu, Sattirajah, & Sizer, 1999; Mendelson et al., 1983; Takeda & Wessel, 1994; Van Tulder, Cherkin, Berman, Lao, & Koes, 1999). These conflicting findings may reflect methodological differences among the studies and differences in study populations. Scientifically rigorous studies are needed to clarify the analgesic effects of acupuncture. The design of such studies would include larger sample sizes, standardized treatment regimens, longer periods of follow-up, and measurement of adequacy of treatment implementation and clinical outcomes (Van Tulder et al., 1999). Studies of Acupuncture in HIV-Infected Persons A search of MEDLINE identified two published articles on the use of acupuncture to relieve pain in persons with HIV/AIDS (Galantino et al., 1999; Shlay et al., 1998). The study by Shlay et al. (1998) randomized 250 persons with HIV-related peripheral neuropathy to receive either a standardized acupuncture regimen (SAR) or acupuncture at irrelevant control points. All participants recorded daily ratings of their pain in a pain diary. After 6 and 14 weeks of treatment, the average weekly pain scores for both the SAR and control groups had decreased from pretreatment levels; however, both groups reported similar reductions in their pain. Blinded neurological examinations at baseline and 14 weeks revealed that the acupuncture groups did not differ with respect to changes in muscle strength, sensation, or reflex activity. Shlay et al. (1998) concluded that SAR was no more effective than control-point acupuncture in relieving HIV-related neuropathic pain. However, methodological limitations of the study make this conclusion questionable. The control condition involved the insertion

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of needles at presumed irrelevant points; however, insufficient data exist to rule out nonspecific effects on pain modulation when these points are stimulated (National Institutes of Health, 1997; Streitberger & Kleinhenz, 1998). Some investigators have asserted that the analgesic effects of acupuncture are not point specific; rather, the proper stimulation of any point can induce peptide-mediated central pain control (Ulett, 1999). The recent development of noninvasive placebo acupuncture needles that are relatively indistinguishable from needles that penetrate the skin may resolve this controversy (Streitberger & Kleinhenz, 1998). In future studies, the nonspecific effects of needle insertion can be tested by comparing SAR, control-point acupuncture, and placebo “needling” at SAR sites. A second limitation involves the potential for nonstandardized implementation of the acupuncture treatment. The study was conducted at 11 sites using multiple acupuncturists. Although all acupuncturists received standardized training on needle insertion and manipulation, it is possible that they differed in how they manipulated the inserted needles, thus threatening the reliability of the treatment. This threat could have been avoided by stimulating the needles with an electrical current, thus standardizing the duration and magnitude of stimulation (King, 1999). In the second study by Galantino et al. (1999), seven persons with HIV-related peripheral neuropathy completed a 30-day study of daily noninvasive electroacupuncture. Noninvasive electroacupuncture involves the administration of electrical current through surface electrodes placed over acupuncture points. Participants self-administered the treatment at home for 20 minutes each day. At the end of the 30-day treatment period, improvements in pain and functional activity were reported by five and six participants, respectively. Limitations of this study include the small sample size and the lack of a control group. Additionally, since all treatments were self-administered in participants’ homes, there was no control over other conditions that could have influenced pain perception (e.g., interactions with significant others, listening to music). Clinical Implications Currently, there are insufficient data to either support or refute the efficacy of acupuncture to relieve

pain in persons with HIV/AIDS. Therefore, patient teaching should focus on safety issues surrounding acupuncture procedures. Although rare, adverse events have been associated with acupuncture. These include transmission of infectious disease, including hepatitis B and C viruses, toxic shock syndrome, organ puncture (most commonly pneumothorax), contact dermatitis, and chondritis from needle insertion in the ear (Ernst & White, 2000; Helms, 1998; Kent, Brondum, Keenlyside, Lafazia, & Scott, 1988). Acupuncture should be avoided in persons with valvular heart disease, coagulopathies, or those taking anticoagulant medications (Vickers & Zollman, 1999), whereas needle insertion in the abdominal and lumbosacral areas is contraindicated in pregnant women (Lao, 1996). Patients should receive treatments only from licensed acupuncturists (L.Acs) who adhere to FDA standards regarding use of sterile, single-use needles (“Medical Devices,” 1996). Capsaicin Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a pungent substance that is derived from hot peppers and has been used as a folk remedy to relieve pain, itching, and constipation (Fusco & Giacovazzo, 1997). Topical capsaicin preparations are commercially available as creams (Zostrix, DoubleCap) and are recommended for the temporary relief of pain associated with arthritis, sprains, and muscle strains. Topical capsaicin has few systemic effects and has been shown to be effective in relieving certain painful musculoskeletal and neuropathic conditions (Craft & Porreca, 1992), therefore, many clinicians have recommended it as an adjunctive therapy to persons with HIV-related peripheral neuropathy (Paice et al., 2000). Analgesic Mechanisms of Capsaicin Capsaicin exerts its analgesic effects by selectively targeting primary afferent C-neurons (Dray, 1992). In the spinal cord, substance P is released from the endings of these neurons leading to activation of central nociceptive pathways. Primary afferent C-neurons conduct impulses generated by noxious stimuli, such as heat and chemicals (Fusco & Giacovazzo, 1997). Following the initial topical application, capsaicin activates afferent C-neurons and produces a severe

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burning sensation (Craft & Porreca, 1992). After repeated applications, the neurons become reversibly desensitized, resulting in analgesia. The mechanisms underlying this desensitization include receptor-dependent opening of ion channels leading to depolarization and eventual depletion of substance P (Rains & Bryson, 1995), and loss of C-fibers in the treated area (Grosskreutz, Quasthoff, Kuhn, & Grafe, 1996). Other neuronal fibers are unaffected by topical capsaicin (Craft & Porreca, 1992), and normal C-fiber responsiveness returns 2 to 4 weeks after cessation of treatment (Roberts, Westerman, Widdop, Kotzmann, & Payne, 1992). Research on Analgesic Effects of Capsaicin Numerous clinical trials and uncontrolled studies have found that topical capsaicin is associated with relief from chronic pain, including postmastectomy pain syndrome (Watson & Evans, 1992), osteoarthritis (Deal et al., 1991), postherpetic neuralgia (Watson et al., 1993), and diabetic peripheral neuropathy (Capsaicin Study Group, 1991). Additionally, a metaanalysis of five trials of topical capsaicin to relieve either neuropathic or postherpetic pain found that capsaicin was associated with significantly greater pain reduction compared with placebo (Kingery, 1997). Capsaicin in HIV-Infected Persons To date, there has been only one published controlled, double-blind clinical trial of topical capsaicin in persons with HIV/AIDS. In that trial, 26 participants with distal symmetrical peripheral neuropathy (DSPN) were randomly assigned to apply either topical capsaicin or topical placebo to their feet four times per day for 4 weeks. At the end of the 4-week treatment period, no differences were found between the two groups with respect to pain relief, sensory perception, quality of life, mood, or functional status. Additionally, a much higher dropout rate occurred in the capsaicin group (67%) than in the placebo group (18%), with half of the capsaicin group dropping out as a result of intense burning caused by the active ingredient (Paice et al., 2000).

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Limitations of this study preclude any definitive conclusions about the efficacy of capsaicin to relieve HIV-related DSPN pain. The small number of participants who completed the study limited the statistical power to detect differences between the groups. Paice et al. (2000) noted that a more aggressive use of oral analgesics during the initial weeks of the study may have enabled participants in the capsaicin group to endure the burning and remain in the study long enough for desensitization to occur. Finally, because the placebo did not contain an ingredient that mimics the burning associated with capsaicin without producing analgesia, such as methyl nicotinate or camphor, participants were likely to know their group assignment. Clinical Implications Because there are insufficient data to draw any conclusions about the efficacy of capsaicin to relieve HIV-related DSPN, teaching should focus on safety issues. Patients who are considering using capsaicin should understand that the treatment is initially painful and that analgesic effects will not be experienced until after several applications. Patients may need to increase their use of oral analgesics until desensitization occurs. Topical capsaicin should not be applied to open or irritated areas on the skin. Hands should be thoroughly washed after applying the cream to avoid spreading to the eyes or mucus membranes.

Depression Infection with HIV is associated with depressive symptoms (Lyketsos et al., 1996). The prevalence of major depression ranges from 4% to 14% in the general population (NIH Consensus Conference, 1992), with prevalence rates approaching 58% in HIVinfected persons (Mayne, Vittinghoff, Chesney, Barrett, & Coates, 1996). Depressive symptoms deleteriously affect general health and functional status and are associated with increased mortality risk (Black, Warrack, & Winokur, 1985; Martin, Cloninger, Guze, & Clayton, 1985a, 1985b; Mayne et al., 1996; Wells et al., 1989). Individual differences

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in the manifestation of depression exist, but common symptoms include sustained feelings of sadness, hopelessness, and worthlessness; changes in energy, appetite, and libido; lowered pain thresholds and exacerbated pain responses; slowed or distorted thought processes; social withdrawal; and suicidal ideation (Buhrich & Judd, 1996; NIH Consensus Conference, 1992). Persons with HIV infection exhibit more suicidal thoughts and behaviors than persons with other life-threatening illnesses and the general population (Cote, Biggar, & Dannenberg, 1992; O’Dowd, Biderman, & McKegney, 1993). No single cause of depression has been identified: Diverse intrapsychic, interpersonal, physiologic, and neurobiologic etiologies have been posited (NIH Consensus Conference, 1992; Peightel, Hardie, & Baron, 1999). Multimodal strategies have been successful in the treatment of depression, which provides evidence that depression has multiple etiologies (Rush, 1998). Consistent with research in psychoneuroimmunology, direct, bidirectional links between the neuroendocrine and immune systems may explain depression’s role in the progression of HIV infection (McCain & Zeller, 1996; Mulder & Antoni, 1992; Patterson et al., 1995). Depression can occur anywhere along the HIV spectrum from acknowledgment of seropositivity to advanced AIDS, although rates may increase as the infection and associated complications progress (Kizer, Green, Perkins, Doebbert & Hughes, 1988; Williams, Rabkin, Remien, Gorman & Ehrhardt, 1991). Depression may manifest as “low-grade” depressive symptoms or major depressive disorders (Perry, 1990). Both mild and severe forms of depression are treatable. The use of antidepressant medications and psychotherapy simultaneously is the standard of care for treatment of depression (Agency for Health Care Policy and Research, 1993; Schneider, 1995). CAM therapies to manage depressive symptoms are becoming increasingly popular and are being used by persons with HIV in conjunction with prescribed medical treatments (Dwyer et al., 1995; Nokes, Kendrew, & Longo, 1995). In this section, the scientific evidence is reviewed on the efficacy of two widely used CAM therapies for managing depression associated with HIV/AIDS: St. John’s Wort and massage therapy.

St. John’s Wort (Hypericum perforatum) St. John’s Wort (Hypericum perforatum) is widely used by persons with mild depression, often in combination with prescribed antidepressants. Because of its relative lack of side effects, St. John’s Wort is often preferred over more costly prescription antidepressants. In 1998, sales increased by 2800% in the United States over the previous year (Brevoort, 1998); European sales approximated U.S.$6 billion (Harrison, 1998). St. John’s Wort has been shown to relieve mild to moderate depression in placebo-controlled trials (Ernst, Rand, Barnes, & Stevenson, 1998; Laakmann, Schule, Baghai, & Kieser, 1998) and has been considered comparable in efficacy to conventional antidepressants (Linde et al., 1996; Vorbach, Arnoldt & Hubner, 1997; Wheatley, 1997). Preliminary findings demonstrate the efficacy of St. John’s Wort for treatment of severe depressive episodes when compared with the tricyclic antidepressant imipramine, but additional confirmatory evidence is warranted (Vorbach et al., 1997). However, Kim, Streltzer, and Goebert (1999) challenge these claims by citing methodological flaws in existing studies. Using more stringent criteria than in prior meta-analyses, they found weaker evidence for the efficacy of St. John’s Wort than claimed previously and concluded that design problems prevent advancing it as an effective antidepressant. The mechanism of action of St. John’s Wort is unknown. Inhibition of monoamine oxidase (MAO) has been suggested (Ernst, 1999) but refuted by others (Cott, 1997; Muller, Rolli, Schafer, & Hafner, 1997). Nathan (1999) reports that rather than acting on the MAO system, St. John’s Wort acts by inhibiting the reuptake of serotonin, norepinephrine, and dopamine, which is similar to the action of common antidepressants. Despite early claims of possible antiretroviral action, subsequent studies have not demonstrated any effects on viral replication (Gulick et al., 1999). Minimal adverse effects have been reported for St. John’s Wort (Miller, 1998), with photosensitivity being the major side effect (Gulick et al., 1992; Gulick et al., 1999). Safety data are not available on long-term use (Peightel et al., 1999). Because St. John’s Wort induces cytochrome P450 isoenzymes, it may interact with food, herbs, and

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drugs. St. John’s Wort has been observed to decrease the effectiveness of warfarin’s anticoagulant properties (Kaminsky & Zhang, 1997), decrease blood levels of digoxin (Johne et al., 1999), and prompt intermenstrual bleeding in young women who take oral contraceptives (LeBel et al., 1999). Supplementation with St. John’s Wort may interfere with the action of antiretroviral medications. In one clinical trial, concomitant use was associated with decreased blood levels of indinavir (Mitchell, 2000). St. John’s Wort should be used cautiously with other known P450 enzyme inducers, such as red wine, ethanol, broccoli, cabbage, brussels sprouts, charcoal-grilled beef, and cigarette smoke (Jobst, McIntyre, St. George, & Whitelegg, 2000). Despite the relatively large number of clinical trials, disparities in nonrandomized experimental and control groups and in operational definitions of both depression and Hypericum prevent advancing St. John’s Wort as an effective treatment, even for mild depression. Well-designed research is needed that includes homogeneous depressed groups who meet standardized diagnostic criteria and who are administered well-characterized preparations of St. John’s Wort (Linde & Mulrow, 2000). In the meantime, patients should be informed that clinical and scientific effectiveness have not been demonstrated nor have the mechanisms of action been identified for St. John’s Wort in the treatment of depression. Clinical Implications The U.S. Food and Drug Administration is working with drug manufacturers to include patient information and warnings on packages of St. John’s Wort. Because photosensitivity has been identified as a side effect, patients who are fair-skinned should be instructed to protect themselves from direct sunlight, to monitor skin for erythema and discomfort, and to avoid other compounds that promote photosensitivity, such as tetracycline hydrochloride and piroxicam. Concomitant use of St. John’s Wort and prescription antidepressants generally should be avoided until the mechanisms of action of Hypericum are known and drug-drug interactions are documented. Supplementing serotonin reuptake inhibitors (SSRI), such as fluoxetine and sertraline, with St. John’s Wort could

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Table 1. Selected CAM Web Sites for Symptom Management http://www.herbs.org http://www.nnlm.nlm.nih.gov/pnr/uwmhg http://dietary-supplements.info.nih.gov http://www.ars-grin.gov/duke/ http://altmed.od.nih.gov/ http://cpmcnet.columbia.edu/dept/rosenthal/factsheets.html http://probe.nalusda.gov http://www.acupuncture.com http://www.amtamassage.org

result in symptoms of serotonism: agitation, dizziness, headache, and sweating (Miller, 1998). Patients and their caregivers can be referred to MEDLINE or the Web sites identified in Table 1 for information about the efficacy of herbal therapies and their possible interaction with prescription and nonprescription drugs. Until safety data become available on its long-term use and studies are conducted that examine its efficacy and side effect profile in persons with HIV, patients should be cautioned about the use of St. John’s Wort for treatment of depression. Massage Therapy Massage therapy is the manipulation of soft tissues through manual techniques that involve applying fixed or movable pressure with such strategies as Swedish massage, sports massage, deep-tissue massage, and neuromuscular massage (“Alternative Medicine,” 1995). Mechanisms of action of massage therapy’s effect on pain reduction and sense of well-being may include the following: (a) arterial and venous blood flow and lymphatic drainage are stimulated, maximizing the supply of oxygen and nutrients to sites of pain; (b) excitability of neurons within the lower motor neuron pool is decreased, resulting in relaxation; (c) passive stretching and elongation of connective and muscular tissue occurs, with a reduction in muscular tightness and tension; and (d) systemic release of endorphins and opiates occurs, resulting in pain reduction and a greater sense of well-being (Goats, 1994; Vujnovich, 1995). Changes in pressure gradients between interstitial spaces and blood vessels are posited to explain massage’s effects on promoting circulation and removing by-products of inflammation and infection. The release of natural painkillers, such as

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endorphins, may explain the effect of massage therapy on depression (Holey & Cook, 1997). The sense of well-being that accompanies massage therapy is antithetical to the sadness and pessimism of depression. Continued investigations into the mechanisms by which massage therapy effects changes in pain and mood are warranted. Massage therapy is widely used by persons with HIV infection (Dwyer et al., 1995; Nokes et al., 1995), but scientific evidence on its efficacy for relieving depressive symptoms is scant. Clinical anecdotes and limited scientific evidence suggest that massage therapy is efficacious in reducing depressive symptoms and enhancing mental well-being in children, adolescents, and adults (Field et al., 1992; Ironson et al., 1996; Weinberg, Jackson, & Kolodny, 1988). It has been suggested that therapies that relieve depressive symptoms may improve immune status parameters. However, findings on the direct effect of massage therapy on immune status in HIV-infected persons have been mixed. One study found no changes in absolute numbers or percentages of CD4+ and CD8+ T lymphocytes or natural killer (NK) cells after weekly 45-minute massage for 12 weeks (Birk, MacArthur, McGrady, & Khuder, 1996). Another found that a daily 45-minute massage for a month increased NK number and cytotoxicity (Ironson et al., 1996). Differences may be related to the frequency with which participants received massage therapy. Because massage therapy research has relied on qualitative-descriptive and single-case designs rather than on double-blind crossover randomized trials, clinical and scientific effectiveness can only be presumed. Lack of comparability among studies on definitions of depression and measures of clinical outcomes, and lack of standardization of the administration of massage, limit interpretation and generalization of the findings. Most studies of massage therapy in HIV-infected persons have been conducted on young White and African American men. Replication is warranted with diverse groups of men and women of all ages from varied socioeconomic and ethnic backgrounds using consensually validated and rigorous designs and measures.

Clinical Implications Massage therapy may be an effective coping mechanism for patients who are depressed and anxious in response to a diagnosis of HIV and its sequelae. According to standards of care for massage therapy, formal training is required to administer the treatment safely. Massage is contraindicated in cases where physiological and psychological intolerance is likely, and modifications may be necessary, for example, for cancer patients (Chamness, 1993; Stater & RankinBox, 1996; Walton, 1998). Persons who are at risk for blood clots or have skin lesions, bruises, fractures, and severe arthritic pain should not receive massage therapy (Breakey, 1982; Joachim, 1983). Because massage may promote the systemic spread of infection and the heat generated by muscular manipulation may exacerbate fever, patients should avoid massage therapy during the early stages of infection and when febrile (Maxwell-Hudson, 1988). Although side effects are minimal, HIV-infected persons should consult with their physicians regarding the appropriateness of massage therapy and be individually assessed to ensure suitability for treatment. Psychological intolerance and physical discomfort may occur during therapy (Andrews, Angone, Cray, Lewis, & Johnson, 1998). Psychological intolerance may relate to individual differences in the need for personal space and privacy (Hill, 1995). Orthostatic hypotension and the possible spread of infection from the lymphatic system to the rest of the body may occur (Goats, 1994). After treatment, patients should be instructed to rise slowly, to sit on the edge of the massage table for a few minutes before standing, and to lower the head if dizziness ensues. The American Massage Therapy Association maintains an online, nationwide directory of licensed massage therapists at www.amtamassage.org.

Conclusion In conclusion, recent reports estimate that up to 70% of persons living with HIV disease use one or more CAM therapies. Despite their widespread use,

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only a few clinical trials have examined the safety and efficacy of frequently used CAM therapies. This small but growing body of evidence suggests that CAM approaches may be beneficial in managing nutritional alterations, pain, and depressive symptoms associated with HIV/AIDS. Nurses caring for persons with HIV/ AIDS have been at the forefront of integrating complementary therapies into their clinical, educational, and research activities. With our continued leadership, additional advances can be made in improving the symptom management and quality of life of our patients.

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Lyketsos, C. G., Hoover, D. R., Guccione, M., Dew, M. A., Wesch, J. E., Bing, E. G., & Treisman, G. J. (1996). Changes in depressive symptoms as AIDS develops. American Journal of Psychiatry, 153, 1430-1437. MacIntyre, R. C., & Holzemer, W. L. (1997). Complementary and alternative medicine with HIV/AIDS. Part II: Selected literature review. Journal of the Association of Nurses in AIDS Care, 8, 25-38. Martin, R. L., Cloninger, C. R., Guze, S. B., & Clayton, P. J. (1985a). Mortality in a follow-up of 500 psychiatric outpatients, I: Total mortality. Archives of General Psychiatry, 42, 47-54. Martin, R. L., Cloninger, C. R., Guze, S. B., & Clayton P. J. (1985b). Mortality in a follow-up of 500 psychiatric outpatients, II: Cause-specific mortality. Archives of General Psychiatry, 42, 58-66. Maxwell-Hudson, C. (1988). The complete book of massage. London: Dorling-Kindersley. Mayne, T. J., Vittinghoff, E., Chesney, M. A., Barrett, D. C., & Coates, T. J. (1996). Depressive affect and survival among gay and bisexual men infected with HIV. Archives of Internal Medicine, 156, 2233-2238. McCain, N. L., & Zeller, J. M. (1996). Psychoneuroimmunological studies in HIV disease. In J. J. Fitzpatrick & J. Norbeck (Eds.), Annual review of nursing research (pp. 23-55). New York: Springer. McDaniel, J. S., Musselman, D., Porter, M., Reed, D., & Nemeroff, C. (1995). Depression in patients with cancer. Archives of General Psychiatry, 52, 89-99. Medical devices: Reclassification of acupuncture needles for the practice of acupuncture. (1996). Federal Register, 61, 6416-6417. Medical Economics. (1999). Physicians’ Desk Reference. Montvale, NJ: Author. Mendelson, G., Selwood, T. S., Kranz, H., Loh, T. S., Kidson, M. A., & Scott, D. S. (1983). Acupuncture-treatment of chronic back pain: A double-blind, placebo-controlled trial. American Journal of Medicine, 74, 49-55. Miller, K., Jones, J., Yanovski, J., Shankar, R., Feuerstien, I., & Falloon, J. (1998). Visceral abdominal fat accumulation associated with the use of indinavir. Lancet, 351, 871-875. Miller, L. G. (1998). Herbal medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Archives of Internal Medicine, 158, 2200-2211. Mitchell, D. (2000). St. John’s Wort causes dangerous interaction with protease inhibitor. Lancet, 355, 547-548. Mulder, C. L., & Antoni M. H. (1992). Psychosocial correlates of immune status and disease progression in HIV-1 infected homosexual men: Review of preliminary findings, and commentary. Psychology and Health, 6, 175-192. Muller, W. E., Rolli, M., Schafer, C., & Hafner U. (1997). Effects of Hypericum extract (LI 160) in biochemical models of antidepressant activity. Pharmacopsychiatry, 30, 102-107. Murray, M., & Pizzorno, J. (1998). Encyclopedia of natural medicine (2nd ed.). Rocklin, CA: Prima.

Nathan, P. J. (1999). The experimental and clinical pharmacology of St. John’s Wort (Hypericum perforatum L). Molecular Psychiatry, 4d, 333-338. National Cholesterol Education Program. (1993). Summary of the second report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults. Journal of the American Medical Association, 269, 3015. NIH Consensus Conference. (1992). Diagnosis and treatment of depression in late life. Journal of the American Medical Association, 268, 1018-1027. National Institutes of Health. (1997). Acupuncture. NIH Consensus Statement, 15, 1-34. Neil, H.A.W., Silagy, C. A., Lancaster, T., Hodgeman, J., Vos, K., Moore, J. W., Jones, L., Cahill, J., & Fowler, G. H. (1996). Garlic powder in the treatment of moderate hyperlipidaemia: A controlled trial and meta-analysis. Journal of the Royal College of Physicians of London, 30, 329-334. Nokes, M., Kendrew, J., & Longo, M. (1995). Alternative/complementary therapies used by persons with HIV disease. Journal of the Association of Nurses in AIDS Care, 6, 19-24. O’Dowd, M. A., Biderman, D. J., & McKegney, F. P. (1993). Incidence of suicidality in AIDS and HIV-positive patients attending a psychiatry outpatient program. Psychosomatics, 34, 33-40. Ostrow, M. J., Cornelisse, P.G.A., Heath, K. V., Craib, K.J.P., Schechter, M. T., O’Shaughnessy, M., Montaner, J.S.G., & Hogg, R. S. (1997). Determinants of complementary therapy use in HIV-infected individuals receiving antiretroviral or antiopportunistic agents. Journal of the Acquired Immune Deficiency Syndromes and Human Retrovirology, 15, 115-120. Paice, J. A., Ferrans, C. E., Lashley, F. R., Shott, S., Vizgirda, V., & Pitrak, D. (2000). Topical capsaicin in the management of HIV-associated peripheral neuropathy. Journal of Pain and Symptom Management, 19, 45-52. Pan, B., Castro-Lopes, J. M., & Coimbra, A. (1996). Activation of anterior lobe corticotrophs by electroacupuncture or noxious stimulation in the anaesthetized rat, as shown by colocalization of Fos protein with ACTH and beta-endorphin and increased hormone release. Brain Research Bulletin, 40, 175-182. Patterson, T. L., Semple, S. J., Temoshok, L. R., Atkinson, J. H., McCutchan, J. A., Straits-Troster, K., Chandler, J. L., & Grant, I., & HIV Neurobehavioral Research Center Group. (1995). Stress and depressive symptoms prospectively predict immune change among HIV-seropositive men. Psychiatry, 58, 299-312. Peightel, J. A., Hardie, T. L., & Baron, D. A. (1999). Complementary/alternative therapies in the treatment of psychiatric illnesses. In J. W. Spencer & J. J. Jacobs (Eds.), Complementary/alternative medicine: An evidence-based approach (pp. 208-247). St. Louis, MO: Mosby. Perry, S. (1990). Organic mental disorders caused by HIV: Update on early diagnosis and treatment. American Journal of Psychiatry, 147, 696-710. Petti, F., Bangrazi, A., Liguori, A., Reale, G., & Ippoliti, F. (1998). Effects of acupuncture on immune response related to

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Streitberger, K., & Kleinhenz, J. (1998). Introducing a placebo needle into acupuncture research. Lancet, 352, 364-365. Sumiya, E., & Kawakita, K. (1997). Inhibitory effects of acupuncture manipulation and focal electrical stimulation of the nucleus submedius on a viscerosomatic reflex anesthetized rats. Japanese Journal of Physiology, 47, 121-130. Takeda, W., & Wessel, J. (1994). Acupuncture for the treatment of pain of osteoarthritic knees. Arthritis Care Research, 7, 118-122. Tyler, V. (1993). The honest herbal: A sensible guide to use of herbs and related remedies (3rd ed.). New York: Pharmaceuticals Products. Ulett, G. A. (1999). Acupuncture and amitryptiline for HIV-related peripheral neuropathic pain [Letter to the editor]. Journal of the American Medical Association, 281, 1270-1271. U.S. Department of Health and Human Services, Food and Drug Administration. (1997). Pharmanex, Inc., administrative proceeding, Public Docket no. 97P-0441: Final decision [Online]. Available: http://www.fda.gov/ohrms/dockets/dockets/97p0441/ans0002.pdf. Van Tulder, M. W., Cherkin, D. C., Berman, B., Lao, L., & Koes, B. W. (1999). The effectiveness of acupuncture in the management of acute and chronic low back pain: A systematic review within the framework of the Cochran Collaboration Back Review Group. Spine, 24, 1113-1123. Vickers, A., & Zollman, C. (1999). ABC of complementary medicine: Acupuncture. BMJ, 319, 973-976. Viraben, R., & Aquilina, C. (1998). Indinavir-associated lipodystrophy. AIDS, 12, F37-F39. Vogl, D., Rosenfeld, B., Breitbart, W., Thaler, H., Passik, S., McDonald, M., & Portenoy, R. K. (1999). Symptom prevalence, characteristics, and distress in AIDS outpatients. Journal of Pain and Symptom Management, 18, 253-262. Vorbach, E. U., Arnoldt, K. H., & Hubner, W. D. (1997). Efficacy and tolerability of St. John’s Wort extract LI 160 versus imipramine in patients with severe depressive episodes according to ICD-10. Pharmacopsychiatry, 30(Suppl. 2), 81-85. Vujnovich, A. (1995). Neural plasticity, muscle spasm and tissue manipulation: A review of the literature. Journal of Manual & Manipulative Therapy, 3, 152-156. Walton, T. H. (1998). Contraindications to massage therapy, Part I. Massage Therapy Journal, 37, 108-112. Warshafsky, S., Kramer, R. S., & Sivak, S. L. (1993). Effect of garlic on total serum cholesterol: A meta-analysis. Annals of Internal Medicine, 119, 599-605. Watson, C. P., & Evans, R. J. (1992). The postmastectomy pain syndrome and topical capsaicin: A randomized trial. Pain, 54, 223-226. Watson, C.P.N., Tyler, K. L., Bickers, D. R., Millikin, L. E., Smith, S., & Coleman, E. (1993). A randomized vehicle-controlled trial of topical capsaicin in the treatment of postherpetic neuralgia. Clinical Therapeutics, 15, 510-526. Weinberg, R., Jackson, A., & Kolodny, K. (1988). The relationship of massage and exercise to mood enhancement. Sport Psychologist, 2, 202-211.

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Wells, K. B., Stewart, A., Hays, R. D., Burnam, M. A., Rogers, W., Daniels, M., Berry, S., Greenfield, S., & Ware J. (1989). The functioning and well-being of depressed patients. Journal of the American Medical Association, 262, 914-919. Wheatley, D. (1997). LI 160, an extract of St. John’s Wort, versus amitriptyline in mildly to moderately depressed outpat i e n t s — A c ont r ol l e d 6- we e k c l i ni c a l t r i a l . Pharmacopsychiatry, 30(Suppl. 2), 77-80. Wheeler, D. A., Gibert, C. L., Launer, C. A., Muurhainen, N., Elion, R. A., Abrams, D. I., & Bartsch, G. E. (1998). Weight loss as a predictor of survival and disease progression in HIV infection. Journal of Acquired Immune Deficiency Syndromes, 18, 80-85.

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Swanson et al. / CAM Therapies to Manage HIV-Related Symptoms Questions

Select the best answer for the following questions: 1. Individuals with chronic illnesses such as HIV/AIDS frequently use complementary or alternative medical practices along with traditional medical therapy. A. True B. False 2. An emerging nutritional alteration in HIV-infected persons who are receiving HAART is A. Wasting B. Cachexia C. Lipodystrophy syndrome D. Protein-calorie malnutrition 3. Which of the following is a common manifestation of lipodystrophy syndrome? A. Decreased breast size in women B. Dyslipidemia C. Decreased abdominal size D. Increased triceps skinfold thickness in the arm 3. The cause of lipodystrophy syndrome is A. Well-established based on consensus B. Due solely to PI therapy C. The result of decreased cholesterol levels D. Not clearly understood and currently under investigation 5. Patients who are taking anticoagulants should avoid consuming large amounts of A. Gingko biloba B. Garlic C. Ginseng D. Ginger 6. Cholestin has been proven to be safe and effective in modifying lipodystrophy-related dyslipidemia in HIV infection. A. True B. False 7. According to traditional Chinese medicine, illness results from A. Disruption in Qi B. Yin dominance C. Spinal misalignment D. Humor imbalance 8. Which of the following is not an analgesic mechanism of acupuncture? A. Release of endogenous opioids B. Activation of descending antinociceptive pathways C. Desensitization of neurons D. Deactivation of limbic structures 9. Which of the following should nurses tell patients who are using capsaicin? A. Wash off ointment 30 minutes after application B. Analgesic effects won’t be experienced until after several applications C. Wrap area with gauze after application D. Do not use systemic analgesics concomitantly 10. Capsaicin induces analgesia by A. Reversing nucleoside-induced toxicity B. Regenerating sensory axons C. Inhibiting dorsal horn neurons D. Desensitizing dorsal horn neurons

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11. Acupuncture is not contraindicated in which of the following? A. Coagulopathies B. Anticoagulant therapy C. Hepatitis B infection D. Valvular disease 12. Symptoms of depression may include all of the following except: A. Inability to experience pleasure B. Pessimism about the future C. Enhanced productivity related to agitation D. Change in weight and nutritional status 13. Goals of treating depression in persons with HIV/AIDS may include A. Altering negative self-thoughts B. Maximizing functional status C. Expanding support resources D. All of the above 14. Teaching patients about using St. John’s Wort in combination with antidepressants should include the following except: A. Safety of the combination has been confirmed in longitudinal studies B. Exercise caution in the ingestion of foods that stimulate P450 enzymes C. Pharmacist or physician should be queried about drug-drug interactions D. Caution should be taken during exposures to direct sunlight 15. Patients on protease inhibitors who are taking Cholestin should be monitored for potential toxic effects due to drug-to-drug interactions of these medications. A. True B. False 16. Adverse effects of garlic may include the following: A. Constipation and irregular bowel movements B. Heartburn, flatulence, GI upset, allergic reactions, skin and breath odor C. Dry mouth, loss of appetite, and nausea and vomiting D. Dry skin, thirst, and frequent urination 17. The state of the science of the use of CAM therapies for treatment of depression is best summarized by which of the following statements: A. Scientific efficacy and effectiveness have been demonstrated for both St. John’s Wort and massage therapy. B. Clinical effectiveness rather than scientific efficacy has been demonstrated for St. John’s Wort and massage therapy. C. Because the mechanism of action of St. John’s Wort is traceable, its efficacy is more easily established than is the Efficacy of massage therapy. D. Costs outweigh the benefits due to patient dissatisfaction with side effects and the relative expense of the treatments Compared with traditional therapies for depression.

Swanson et al. / CAM Therapies to Manage HIV-Related Symptoms

ANSWER/EVALUATION FORM Continuing Education Credit (1.2 contact hours) Answer Form: CE 200 Complementary and Alternative Therapies to Manage HIV-Related Symptoms (CAM)

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EVALUATION FORM To evaluate this continuing education offering, please respond to each question below by checking “Yes” or “No.” Check: Yes

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1. Can you discuss two CAM therapies that have potential for managing HIV-related dyslipidemia?

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2. Can you discuss the analgesic mechanisms of acupuncture and capsaicin?

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3. Can you identify teaching implications for persons with HIV/AIDS who use acupuncture or capsaicinto manage their pain?

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4. Can you discuss the state of the science on the use of CAM therapies for the treatment of depression?

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5. Were the objectives relevant to the goal of this program?

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6. Was the teaching method effective?

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7. Did this offering meet your objectives?

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8. How much time did it take to complete this offering? ___________ 9. Additional comments: