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The HIV wasting syndrome: a review.

The HIV wasting syndrome and other HIV-associated weight loss is a major problem in HIV-infected patients. The available data strongly suggest that wasting is associated with decreased survival. It may also further impair immune function. A variety of etiologies probably contribute to this wasting, including hypermetabolism, alterations in metabolism, lessened oral intake, malabsorption, cytokine effects, and endocrine dysfunction. The relative contributions of each of these etiologies to wasting probably varies considerably from patient to patient. Successful treatment calls for identification of possible etiologies of wasting in the individual patient with AIDS. Further treatment may include treating underlying conditions and controlling such symptoms as diarrhea, nausea, or fever. Nutritional support, including both parenteral and enteral nutrition, has shown some promise of efficacy, and a variety of drugs appears to be helpful. Future treatment to reverse wasting may include the use of several of these agents in combination. Currently, there is much that clinicians can do to evaluate and treat the HIV wasting syndrome, with significant potential benefits to their patients.

Cachexia↗

Endocrine function in the HIV wasting syndrome.

We compared endocrine function in patients with the HIV wasting syndrome with other HIV-positive patients without wasting to determine associations between endocrine dysfunction and wasting. Sixty-six HIV-seropositive patients were evaluated by thyroid, gonadal, and adrenal function tests. Fourteen of these patients met the clinical definition of wasting. Total and free testosterone levels were significantly lower in patients with wasting compared with patients without wasting with both similar and higher mean CD4 counts. Prolactin levels were significantly higher, and cortisol levels were higher with borderline significance in patients with wasting compared with patients with similar CD4 counts without wasting. These findings suggest that endocrine function in the HIV wasting syndrome differs from that of HIV-infected patients without wasting, which may have implications about the pathogenesis and treatment of the HIV wasting syndrome.

Emaciation↗

Micronutrient concentrations in the HIV wasting syndrome.

OBJECTIVE: We measured micronutrient values in patients with the HIV wasting syndrome and in other HIV-seropositive patients to determine whether specific micronutrient deficiencies were associated with the wasting syndrome. METHODS: Serum from 47 HIV-seropositive patients was evaluated for concentrations of vitamin A, B6, B12, C, D, E, folate, the mineral zinc, carotene and glutathione. Comparisons were made between groups stratified by CD4 cell count and wasting/non-wasting status. RESULTS: Mean serum levels were significantly lower for vitamin A (P = 0.04), folate (P = 0.04) and carotene (P = 0.06) in patients with the HIV wasting syndrome than in non-wasting patients with comparable CD4 cell counts. Values of vitamins A, B6, C, D, carotene and glutathione were below the normal range in over 10% of HIV-seropositive patients in this study. CONCLUSION: Decreased micronutrient concentrations are common in HIV-infected patients and occur more frequently in patients with the wasting syndrome. Clinicians may wish to evaluate HIV-seropositive patients with wasting for individual micronutrient deficiencies, although they should note that particular deficiencies may be only part of the larger picture of malabsorption and undernutrition.

CD4-Positive T-Lymphocytes↗

HIV wasting syndrome: treatment update.

OBJECTIVE: To review the pathophysiology and treatment of HIV wasting syndrome. DATA SOURCES AND STUDY SELECTION: MEDLINE searches (January 1987-September 1997) of the English-language medical literature were conducted. Bibliographies were also selected during a manual review. DATA SYNTHESIS: HIV-related weight loss, often referred to as HIV wasting syndrome, is a common manifestation of advanced HIV infection. Wasting in HIV involves the preferential loss of lean body mass with a paradoxical preservation of body fat. The etiology of wasting appears to be the result of many factors, which may include decreased caloric intake, malabsorption, alterations in energy expenditure and metabolism, cytokine effects, and endocrine dysfunction. Pharmacologic treatment options include appetite stimulants (e.g., dronabinol, megestrol acetate), cytokine inhibitors (e.g., thalidomide, cyproheptadine, ketotifen, pentoxifylline, fish oil, N-acetylcysteine), and anabolic agents (e.g., testosterone, nandrolone, oxandrolone, recombinant human growth hormone). CONCLUSIONS: Wasting associated with HIV has a high morbidity and mortality rate if not adequately managed. Therapeutic strategies include appetite stimulants, cytokine inhibitors, and growth-promoting agents. Selection of the appropriate agent(s) depends on the underlying cause for weight loss, adverse effects, and cost of therapy.

HIV Infections↗

Testosterone therapy in HIV wasting syndrome: systematic review and meta-analysis.

Many HIV patients develop weight loss, which increases morbidity and mortality. We aimed to assess the effects of testosterone therapy on lean body mass, total body weight, over-all exercise functional capacity, and perceived quality of life in patients with HIV wasting syndrome and its adverse effects. We systematically reviewed randomised, placebo-controlled trials that compared the effects of testosterone therapy with placebo in HIV patients with wasting. Eight trials met the inclusion criteria and 417 randomised patients were included. Only six trials used lean-body mass, fat-free mass, or body-cell mass as outcome measures. The meta-analysis of the six trials showed a difference in the lean body mass between the testosterone group and placebo group of 1.22 kg (95% CI 0.23-2.22) for the random effect model and 0.51 kg (0.09-0.93) for fixed effect. However, the difference was much greater in the three trials that used the intramuscular route-3.34 kg in the post-hoc analysis. All eight trials included total body weight as an outcome measure, the meta-analysis of which showed a difference of 1.04 kg (-0.01-2.10) between testosterone group and placebo group by random effect and 0.63 kg (-0.01-1.28) for fixed effect models. Over-all, the incidence of adverse effects is similar in both groups. Testosterone therapy has been shown in this review to increase lean body mass more than placebo. The increase is even greater if the therapy is given intramuscularly. There is also a small positive effect in total body weight. The study is, however, limited by the small numbers and heterogeneity of the population, which potentially introduced bias into the methods and results. Testosterone therapy may be considered in patients with HIV wasting syndrome to reverse muscle loss, but there is a concern about the adverse metabolic effects of long-term testosterone administration and long-term follow-up for these patients is needed.

Body Mass Index↗

HIV wasting syndrome in the United States.

OBJECTIVE: To describe the characteristics of individuals > or = 13 years of age with HIV wasting syndrome in the United States and US territories. DESIGN: Retrospective review of national AIDS case surveillance data. METHODS: Data for the 147,225 individuals with AIDS reported to the Centers for Disease Control from 1 September 1987 to 31 August 1991 were reviewed. The frequency of HIV wasting syndrome and its association with demographic and exposure category variables and with other AIDS-indicator diseases were assessed. RESULTS: A total of 10,525 (7.1%) had wasting syndrome as the only AIDS-indicator condition, and 15,726 (10.7%) had wasting syndrome plus at least one other AIDS-indicator condition. Patients with wasting syndrome as the only AIDS diagnosis were more likely to be female, to be black or Hispanic, and to have a mode of HIV exposure reported as injecting drug use, heterosexual contact, or transfusion/hemophilia. The proportion of AIDS patients reported with wasting syndrome varied by geographic distribution, ranging from 11% in the northeastern United States to 47% in Puerto Rico. The association between HIV wasting syndrome and Hispanic ethnicity was due to the much higher prevalence of wasting syndrome reported in Puerto Rican AIDS patients. The other AIDS-indicator conditions most strongly associated with wasting syndrome were isosporiasis, pulmonary candidiasis, esophageal candidiasis, HIV encephalopathy, chronic mucocutaneous herpes simplex, and coccidioidomycosis. CONCLUSIONS: The association between HIV wasting syndrome and injecting drug use, and the significant racial/ethnic and geographic differences in prevalence of this AIDS diagnosis may reflect differences in diagnostic and reporting practices and/or access to medical care.

AIDS-Related Opportunistic Infections↗

Diabetes mellitus associated with recombinant human growth hormone for HIV wasting syndrome.

Recombinant human growth hormone (rhGH) is an important treatment option for patients with human immunodeficiency virus (HIV) wasting syndrome. Side effects of rhGH are minimal when administered at physiologic and moderately high dosages, as seen in growth hormone deficiency and Turner's syndrome, respectively. The dosage of rhGH is significantly higher to treat wasting syndrome and still is being studied to determine its long-term efficacy and safety. Individuals with HIV infection are at increased risk for adverse effects due to polypharmacy, immune system alterations, and treatment with newer agents that lack long-term safety data. In addition, rhGH's potential for side effects becomes greater when given at high dosages for wasting syndrome. Clinically significant hyperglycemia developed in an HIV-positive man who started rhGH for wasting syndrome 38 days before the diagnosis of diabetes mellitus.

Blood Glucose↗

The safety and pharmacokinetics of single-agent and combination therapy with megestrol acetate and dronabinol for the treatment of HIV wasting syndrome. The DATRI 004 Study Group. Division of AIDS Treatment Research Initiative.

This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients (mean CD4+ count, 59 cells/microliter) were randomized to one of four treatment arms: dronabinol 2.5 mg twice/day (D); megestrol acetate 750 mg/day (M750); megestrol acetate 750 mg/day+dronabinol 2.5 mg twice/day (M750+D); or megestrol acetate 250 mg/day+dronabinol 2.5 mg twice/day (M250+D). After therapy initiation, 47 patients returned for at least one visit, and 39 completed the planned 12 weeks of study visits. Occurrence of adverse events, drug discontinuation, new AIDS-defining conditions, or CD4+ T lymphocyte changes were not statistically significantly different among arms. Serious adverse events assessed as related to dronabinol included CNS events (e.g., confusion, anxiety, emotional lability, euphoria, hallucinations) and those assessed as related to megestrol acetate included dyspnea, liver enzyme changes, and hyperglycemia. The mean weight change +/- SE over 12 weeks was as follows: D, -2.0 +/- 1.3 kg; M750, +6.5 +/- 1.1 kg; M750+D, +6.0 +/- 1.0 kg; and M250+D, -0.3 +/- 1.0 kg (difference among treatment arms, p = 0.0001). Pharmacokinetic parameters measured after 2 weeks of therapy for M750 were Cmax = 985 ng/ml and AUC = 22,487 ng x hr/ml, and for dronabinol and its active metabolite (HO-THC), respectively, were Cmax = 2.01; 4.61 ng/ml and AUC = 5.3; 23.7 ng x hr/ml. For megestrol acetate, but not dronabinol, there was a positive correlation at week 2 between both Cmax and AUC with each of the following: (1) weight change, (2) breakfast visual analog scale for hunger (VASH) score, and (3) dinner VASH score.

Adolescent↗

[HIV wasting syndrome].

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Antiretroviral Therapy, Highly Active↗