Category Archives: Wasting syndrome

Wasting syndrome

– Christian Hoffmann –

Wasting syndrome is defined as involuntary weight loss of at least 10% of original body weight accompanied by persistent diarrhea (at least two bowel movements daily for more than 30 days) or extreme fatigue and/or fever without apparent infectious etiology. With thorough and competent searching, a specific causative agent can usually be found for wasting syndrome because it is essentially a classical exclusion diagnosis and really more of an epidemiological instrument than a specific disease. Although previously a very frequent condition, wasting syndrome has become rare today. For example, in a large study conducted in 2000, only 14% of patients still indicated having lost more than 10% of their original body weight (Wanke 2000). Rates are even higher in intravenous drug users (Campa 2005). Weight loss remains an independent risk factor for mortality, even in the HAART era, and every patient should be weighed regularly. In one large study, mortality risk in patients with a loss greater than 10% of body weight was more than four to six times higher than that of patients with stable body weight (Tang 2002). Patients with classic wasting syndrome are often extremely weak. That said, the risk for opportunistic infections is significantly elevated (Dworkin 2003). There is also cognitive impairment in these patients (Dolan 2003).

Diagnosis

The causes of wasting syndrome are complex. First, it is necessary to exclude or treat opportunistic infections (TB, MAC, cryptosporidiosis and microsporidiosis). If none are found, then several reasons remain that may contribute, even in combination, to wasting syndrome. These include:  metabolic disorders, hypogonadism, poor nutrition and malabsorption syndromes (overview: Grinspoon 2003).

Consequently, a thorough patient history is extremely beneficial. Does the patient have a sensible diet? How are meals distributed throughout the day? Is the patient depressed? Which drugs (ART) are being taken? Distinction from antiretroviral-induced lipoatrophy (d4T/ ddI) is often difficult. Significant weight loss also occurs frequently on interferon (Garcia-Benayas 2002), but rapidly resolves after finishing treatment. In addition, hypogonadism should be ruled out with the measurement of testosterone. While there are several simple tests for malabsorption syndromes, it is prudent to start with testing albumin as well as TSH and cholesterol levels.

Further tests such as D-xylose absorption or biopsies of the small intestine should only be initiated after consulting with a gastroenterologist. Other tests, such as DEXA, densitrometry, bioelectrical impedance analysis, should be conducted in centers experienced with wasting syndrome in AIDS patients to determine the patients’ body composition.

Therapy

Wasting syndrome always requires competent diet counseling. Exercise, if possible, is also good. Of course, both only have limited success. Supportive parenteral nutrition only helps if there are problems with absorption (Kotler 1990, Melchior 1996). Effective ART, ideally without drugs that cause lipoatrophy such as d4T or ddI, and possibly even omitting nucleoside analogs completely, is ideal. Severe lipoatrophy may require complete omission of nucleoside analogs (see chapter on Nuke sparing).

Beyond this, many kinds of drug treatment have been attempted. However, these have limited success and are often problematic.

Megestrol acetate, a synthetic gestagenic hormone, shows some benefit as an appetite stimulant in wasting syndrome, as demonstrated in some studies (Von Roenn 1994, Mulligan 2006). Its side effects are ones typically associated with steroids, including induced hypogonadism which should always be evaded, especially in cases of wasting syndrome. As a result, it is not widely nor currently recommended that this drug be used.

Dronabinol, the main active ingredient in marijuana, has been licensed in the US since 1985 as Marinol®, and may be prescribed for pharmacy formulation as drops or hard gel capsules. This drug is certainly attractive for many patients and sometimes actively demanded. Prescription should be carefully considered, particularly in view of the significant cost associated with the medication.  In some European countries, dronabinol costs approximately 600 Euros per month for the usual dose of 5 mg tid. Without a clear diagnosis of wasting syndrome, clarity about the health insurance coverage and communication with the insurance company may minimize substantial problems. In generally, some health insurances reject the request. The effect on wasting syndrome is moderate at best, if detectable at all (Beal 1995). It tends to be even weaker than megestrol acetate (Timpone 1997).

Hypogonadism, a frequent condition of patients with wasting syndrome, calls for the measurement of testosterone age-dependent levels. If the levels are low, then testosterone substitution has proven itself  as useful, both for weight gain and quality of life (Grinspoon 1998). A dose of 250 mg testosterone is given i.m. every 3-4 weeks, and there is a variety of less expensive generic names. The effect is sustained, even with long-term use (Grinspoon 1999). If testosterone levels are normal, then the substitution in cases of wasting syndrome is not indicated. In women, one should exercise caution when administering androgenic hormones. Other anabolic steroids are available in addition to testosterone, such as oxandrolone or nandrolone (Gold 2006, Sardar 2010). Although possibly more effective than testosterone, these drugs are commonly associated with other side effects, particularly those related to the liver (Corcoran 1999). Positive effects have been demonstrated with the anabolic steroid oxymetholone in a small, double-blind, randomized study (Hengge 2003). However, extremely high elevation of transaminases have been observed.

High costs and side effects have limited the use of recombinant human growth hormones (rhGH), for which long-term data is still not available (Mulligan 1993, Schambelan 1996). However, the results of a recent metaanalysis suggest that growth hormones may be more effective than anabolic steroids or testosterone in wasting syndrome (Moyle 2004). Common adverse events with rhGH therapy include blood glucose elevations, arthralgia, myalgia, and peripheral edema, but these usually respond to dose reduction or drug discontinuation (review: Gelato 2007).

References

Beal JE, Olson R, Laubenstein L, et al. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS. J Pain Symptom Manage 1995;10:89-97.

Corcoran C, Grinspoon S. Treatments for wasting in patients with the acquired immunodeficiency syndrome. NEJM 1999, 340:1740-50.

Dolan S, Montagno A, Wilkie S, et al. Neurocognitive Function in HIV-Infected Patients With Low Weight and Weight Loss. J AIDS 2003; 34: 155-64.

Dworkin MS, Williamson JM. AIDS wasting syndrome: trends, influence on opportunistic infections, and survival. J AIDS 2003; 33: 267-73.

Garcia-Benayas T, Blanco F, Soriano V. Weight loss in HIV-infected patients. N Engl J Med 2002, 347: 1287-8.

Gelato M, McNurlan M, Freedland E. Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment. Clin Ther 2007;29:2269-88.

Gold J, Batterham MJ, Rekers H, et al. Effects of nandrolone decanoate compared with placebo or testosterone on HIV-associated wasting. HIV Med 2006, 7:146-55.

Grinspoon S, Corcoran C, Anderson E, Hubbard J, Basgoz N, Klibanski A. Sustained anabolic effects of long-term androgen administration in men with AIDS wasting. Clin Infect Dis 1999, 28:634-636.

Grinspoon S, Corcoran C, Askari H, et al. Effects of androgen administration in men with the AIDS wasting syndrome: a randomized, double-blind, placebo-controlled trial. Ann Intern Med 1998;129:18-26.

Grinspoon S, Mulligan K. Weight loss and wasting in patients infected with human immunodeficiency virus. Clin Infect Dis 2003; 36: S69-78.

Hengge UR, Stocks K, Faulkner S, et al. Oxymetholone for the treatment of HIV-wasting: a double-blind, randomized, placebo-controlled phase III trial in eugonadal men and women. HIV Clin Trials 2003; 4:150-63.

Kotler DP, Tierney AR, Culpepper-Morgan JA, Wang J, Pierson RN Jr. Effect of home total parenteral nutrition on body composition in patients with AIDS. J Parenter Enteral Nutr 1990;14:454-458.

Melchior J, Chastang C, Gelas P, et al. Efficacy of 2-month total parenteral nutrition in AIDS patients: a controlled randomized prospective trial. AIDS 1996;10:379-384.

Mulligan K, Grunfeld C, Hellerstein MK, et al. Anabolic effects of recombinant human growth hormone in patients with wasting associated with HIV infection. J Clin Endocrinol Metab 1993, 77:956-962.

Mulligan K, Zackin R, Von Roenn JH, et al. Testosterone supplementation of megestrol therapy does not enhance lean tissue accrual in men with hiv-associated weight loss: A randomized, double-blind, placebo-controlled multicenter trial. J Clin Endocrinol Metab 2006 Nov 7;

Sardar P, Jha A, Roy D, Majumdar U, et al. Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial. HIV Clin Trials 2010, 11:220-9.

Schambelan M, Mulligan K, Grunfeld C, et al. Recombinant human growth hormone in patients with HIV-associated wasting: a randomized, placebo-controlled trial. Ann Intern Med 1996, 125:873-882.

Tang AM, Forrester J, Spiegelman D, et al. Weight loss and survival in HIV-positive patients in the era of highly active antiretroviral therapy. J AIDS 2002, 31: 230-6.

Timpone JG, Wright DJ, Li N, et al. The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. AIDS Res Hum Retroviruses 1997, 13:305-15.

Von Roenn JH, Armstrong D, Kotler DP, et al. Megesterol acetate in patients with AIDS-related cachexia. Ann Intern Med 1994, 121:393-399.

Wanke CA, Silva M, Knox TA, et al. Weight loss and wasting remain common complications in individuals infected with HIV in the era of highly active antiretroviral therapy. Clin Infect Dis 2000, 31:803-5.

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Filed under 11. Opportunistic Infections, Part 3 - AIDS, Wasting syndrome