Vitamin D status and its association with morbidity including wasting and opportunistic illnesses in HIV-infected women in Tanzania.

Vitamin D has a potential role in preventing HIV-related complications, based on its extensive involvement in immune and metabolic function, including preventing osteoporosis and premature cardiovascular disease. However, this association has not been examined in large studies or in resource-limited settings. Vitamin D levels were assessed in 884 HIV-infected pregnant women at enrollment in a trial of multivitamin supplementation (excluding vitamin D) in Tanzania. Information on HIV related complications was recorded during follow-up (median, 70 months). Proportional hazards models and generalized estimating equations were used to assess the relationship of vitamin D status with these outcomes. Women with low vitamin D status (serum 25-hydroxyvitamin D<32 ng/mL) had 43% higher risk of reaching a body mass index (BMI) less than 18 kg/m(2) during the first 2 years of follow-up, compared to women with adequate vitamin D levels (hazard ratio [HR]: 1.43; 95% confidence intervals: [1.03-1.99]). The relationship between continuous vitamin D levels and risk of BMI less than 18 kg/m(2) during follow-up was inverse and linear (p=0.03). Women with low vitamin D levels had significantly higher incidence of acute upper respiratory infections (HR: 1.27 [1.04-1.54]) and thrush (HR: 2.74 [1.29-5.83]) diagnosed during the first 2 years of follow-up. Low vitamin D status was a significant risk factor for wasting and HIV-related complications such as thrush during follow-up in this prospective cohort in Tanzania. If these protective associations are confirmed in randomized trials, vitamin D supplementation could represent a simple and inexpensive method to improve health and quality of life of HIV-infected patients, particularly in resource-limited settings.

Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PURPOSE: We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. METHODS: In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. RESULTS: Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). CONCLUSION: Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

Interleukin-6 and human immunodeficiency virus load, but not plasma leptin concentration, predict anorexia and wasting in adults with pulmonary tuberculosis in Malawi.

BACKGROUND: Wasting is a prominent feature of tuberculosis and may be more severe among individuals with HIV coinfection. It is likely that several biological mechanisms, including the anorexia of infection, are contributing to wasting. OBJECTIVE: The purpose of this study was to determine whether leptin concentrations, in relation to the inflammatory cytokine response and level of HIV infection, are contributing to loss of appetite and wasting in adults with pulmonary tuberculosis and HIV infection. DESIGN: We characterized plasma leptin concentrations in relationship with self-reported loss of appetite, body mass index, fat mass (FM), IL-6, and HIV load in a cross-sectional study of 500 adults who presented with pulmonary tuberculosis in Zomba, Malawi. RESULTS: Plasma leptin concentrations, associated with FM, significantly decreased by increasing tertile of plasma HIV load (P = 0.0001). Leptin concentrations were inversely associated with plasma IL-6 concentrations after adjusting for sex, age, FM, and HIV load. Plasma leptin concentrations were associated with neither loss of appetite nor wasting. Inflammation, reflected by increased IL-6 concentrations, was associated with loss of appetite (odds ratio, 3.41; 95% confidence interval, 1.91-6.09), when adjusted for sex, age, FM, leptin concentrations, and HIV load. A high plasma HIV load was associated with severe wasting, defined as body mass index less than 16.0 kg/m2 (odds ratio, 2.14; 95% confidence interval, 1.09-4.19) when adjusted for sex, age, IL-6, FM, and leptin concentrations. CONCLUSION: This study suggests that the anorexia and wasting seem primarily determined by the level of inflammation and the level of HIV infection in patients with tuberculosis and HIV coinfection.

Tumor necrosis factor-alpha levels in patients with HIV with wasting in South Asia.

Tumor necrosis factor (TNF)-alpha is thought to play an important role in wasting; but TNF-alpha levels have not been consistently found to be high in AIDS wasting. We conducted this study to determine any correlation between TNF-alpha levels and wasting in HIV-positive patients in a developing country. TNF-alpha levels were measured in four groups of patients: Group 1, HIV/AIDS with wasting (n = 25); group 2, HIV/AIDS without wasting (n = 47); group 3, HIV-negative patients with tuberculosis with wasting (n = 25); and group 4, healthy controls (n = 25). Wasting was defined as a body bass index (BMI)

Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial.

BACKGROUND: Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. METHODS: In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. RESULTS: Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P<.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. CONCLUSION: Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases.

Diarrhea and reduced levels of antiretroviral drugs: improvement with glutamine or alanyl-glutamine in a randomized controlled trial in northeast Brazil.

The effects of therapy with glutamine and alanyl-glutamine on diarrhea and antiretroviral drug levels in patients with acquired immune deficiency syndrome (AIDS) were examined in a randomized, double-blinded, placebo-controlled study in northeast Brazil. Patients with AIDS and with diarrhea and/or wasting were randomized into 4 groups to determine the efficacy of glutamine or high- or low-dose alanyl-glutamine given for 7 days, compared with isonitrogenous glycine given to control subjects. All patients in whom baseline antiretroviral drug levels were determined had low levels 2 h after dosing. Gastrointestinal symptom scores improved with receipt of high-dose alanyl-glutamine (P<.05) or glutamine (P<.01). Antiretroviral drug levels increased in patients given alanyl-glutamine (P=.02) or glutamine (P=.03) by 113% (P=.02) and 14% (P=.01), respectively. Antiretroviral drug resistance mutations were common in all groups. The dose-related efficacy of alanyl-glutamine and glutamine in treating diarrhea and in increasing antiretroviral drug levels shows that these supplements may help to improve therapy for patients with AIDS who have diarrhea and/or wasting in developing, tropical areas.

Oxymetholone for the treatment of HIV-wasting: a double-blind, randomized, placebo-controlled phase III trial in eugonadal men and women.

BACKGROUND: Despite highly active antiretroviral therapy (HAART), chronic involuntary weight loss still remains a serious problem in the care of HIV patients due to various alterations in energy metabolism and endocrine regulation. Previous studies in HIV-positive men undergoing androgen replacement therapy or treatment with recombinant growth hormone (rGH) have shown partial restoration of lean body mass (LBM), but these treatments have largely not been sufficiently studied in eugonadal individuals. METHOD: A double-blind, randomized, placebo-controlled trial of 89 HIV-positive eugonadal women and men with wasting assigned to the anabolic steroid oxymetholone (50 mg bid or tid) or placebo for 16 weeks was performed. Body weight, bioimpedance measurements, quality of life parameters, and appetite were analyzed. RESULTS: Oxymetholone led to a significant weight gain of 3.0 +/- 0.5 and 3.5 +/- 0.7 kg in the tid and bid groups, respectively (p <.05 for each treatment versus placebo), while individuals in the placebo group gained an average of 1.0 +/- 0.7 kg. Body cell mass (BCM) increased in the oxymetholone bid group (3.8 +/- 0.4 kg; p <.0001) and in the oxymetholone tid group (2.1 +/- 0.6 kg; p <.005). Significant improvements were noted in appetite and food intake, increased wellbeing, and reduced weakness by self-examination. The most important adverse event was liver-associated toxicity. Overall, 43% of patients in the tid group, 25% of patients in the bid oxymetholone group, and 8% in the placebo group had a greater than 5 times baseline increase for ALT, AST, or gamma GT, while other adverse events were not increased over placebo. CONCLUSION: Oxymetholone can be considered an effective anabolic steroid in eugonadal male and female patients with AIDS-associated wasting. The bid (100 mg/day) regimen appeared to be equally effective to the tid (150 mg/day) regimen in terms of weight gain, LBM, and BCM and was associated with less liver toxicity.

Cytokine responses differ by compartment and wasting status in patients with HIV infection and healthy controls.

Inflammatory cytokines are implicated in the loss of lean tissue that occurs in patients with inflammatory and infectious diseases, including HIV infection. However, it is not known whether plasma levels or cellular production of cytokines, or their antagonists, are more closely related to lean tissue loss. We studied whether plasma cytokine analysis could substitute for PBMC production assays in studies of nutrition status and disease state, and if cytokine antagonists could offer an alternative in assessing cytokine status. We used a bout of moderately difficult exercise to perturb cytokine production in 12 adults with HIV without wasting, 10 adults with HIV wasting, and nine healthy controls. Plasma and peripheral blood mononuclear cell (PBMC) production of interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra) and soluble TNF receptor type II (sTNFrII) were measured at baseline and 2, 6, 24 and 168h following exercise. PBMC production of IL-1beta, TNF-alpha and IL-6 were all higher in the HIV-infected patients without wasting than in the controls (P<0.05) or the patients with AIDS wasting (P<0.05). Plasma concentrations of TNF-alpha and IL-6 were higher in the HIV wasted patients than in the controls (P<0.05). Both plasma and PBMC levels of sTNFrII were higher in HIV patients, regardless of wasting, than in controls. These data suggest that the PBMC cytokine compartment is more sensitive to nutritional and metabolic abnormalities than is the plasma compartment. PBMC production of IL-1beta, IL-6 and TNF-alpha best distinguish between HIV patients with and without wasting, while plasma concentrations of IL-6 and TNF-alpha are elevated in AIDS wasting, but do not reliably distinguish patients with wasting from HIV-infected patients without wasting.

Soluble tumour necrosis factor alpha receptor 2, a serum marker of resistance to the anabolic actions of growth hormone in subjects with HIV disease.

Therapies are still being sought for the prevention of loss of body weight and lean body mass in HIV disease. The purpose of the present study was to identify a serum marker that would help in selecting patients who may be appropriate candidates for the use of anabolic agents, such as growth hormone, to restore lean body mass. This study included 26 HIV-infected patients and nine healthy controls, assessed previously for the effectiveness of 2 weeks of growth hormone administration in the stimulation of protein synthesis in skeletal muscle. Serum levels of interleukins-1beta, -6 and -10 were not useful predictors of the anabolic response to growth hormone. Serum concentrations of tumour necrosis factor alpha (TNFalpha) were significantly elevated (P<0.05) in patients with AIDS and AIDS-related weight loss, and there was a significant correlation between the serum concentration of interleukin-1 receptor antagonist and stage of disease (P=0.03). However, the serum concentration of the soluble TNFalpha receptor type 2 was most predictive of an inability of muscle protein synthesis to respond anabolically to growth hormone (r=-0.42, P=0.01). These data suggest that inflammation impacts on the responsiveness of muscle tissue to an anabolic stimulus, and that the soluble TNFalpha receptor type 2 provides a useful serum marker for metabolic dysfunction in HIV disease, which can be used to identify individuals likely to respond to growth hormone-based anabolic therapy.

Body composition and nutritional parameters in HIV and AIDS patients.

Undernutrition is a frequent complication of evolutive and chronic HIV (human immunodeficiency virus) infection characterized by bodyweight loss and changes in body composition. The Centers for Disease Control and Prevention define AIDS wasting as involuntary loss of more than 10% of body weight, plus more than 30 days of either diarrhea, or weakness and fever. Wasting syndrome has been considered as a case definition of the AIDS disease since 1987. Wasting syndrome is clearly linked to disease progression and death. Despite the progress under the era of highly active antiretroviral therapy (HAART), wasting is still a problem for people with AIDS. A small part of the weight lost is fat. More important is the loss of "lean body mass", which is mostly muscle. Body composition changes during HIV infection are different from those observed in food deprivation. Under the era of HAART, a HIV-associated adipose redistribution syndrome (HARS) was described that associates subcutaneous lipoatrophy and abdominal obesity linked to various metabolic disorders. Several factors contribute to wasting syndrome. Not only low food intake and poor nutrient absorption, but mainly altered metabolism (increased resting energy expenditure) and specific disturbances in protein turnover, which is also increased. Nutritional evaluation of HIV-infected patients should include the measurement of body composition and analysis of nutritional parameters, including albumin, transthyretin and C-reactive protein. Transthyretin seems to be particularly useful to follow the recovery period of malnutrition.

Mechanisms of androgen deficiency in human immunodeficiency virus-infected women with the wasting syndrome.

Although prior studies suggest reduced androgen levels in women with acquired immune deficiency syndrome wasting, little is known regarding the regulation of adrenal and ovarian androgen secretion in such patients. We investigated ovarian and adrenal function in 13 human immunodeficiency virus-infected women with acquired immune deficiency syndrome wasting and 21 age- and body mass index-matched healthy control subjects studied in the early follicular phase. Subjects received hCG (5000 U, im) on d 1 and Cosyntropin (0.25 mg, i.v.) on d 3 after dexamethasone (1 mg, orally, at 2400 h) pretreatment on d 2. At baseline, human immunodeficiency virus-infected subjects demonstrated significantly reduced T [18 +/- 2 vs. 25 +/- 2 ng/dl (0.6 +/- 0.1 vs. 0.9 +/- 0.1 nmol/liter); P = 0.02], free T [1.5 +/- 0.1 vs. 2.4 +/- 0.2 pg/ml (5.3 +/- 0.5 vs. 8.3 +/- 0.6 pmol/liter); P = 0.001], androstenedione [119 +/- 6 vs. 162 +/- 14 ng/dl (4.16 +/- 0.20 vs. 5.66 +/- 0.48 nmol/liter); P = 0.02], and dehydroepiandrosterone sulfate [0.96 +/- 0.17 vs. 1.55 +/- 0.19 microg/ml (2.6 +/- 0.5 vs. 4.2 +/- 0.5 micromol/liter); P = 0.047] levels compared with the control subjects. T [8 +/- 2 vs. 6 +/- 2 ng/dl (0.3 +/- 0.1 vs. 0.2 +/- 0.1 nmol/liter); P = 0.48], free T [0.5 +/- 0.2 vs. 0.4 +/- 0.1 pg/ml (1.7 +/- 0.7 vs. 1.5 +/- 0.5 pmol/liter); P = 0.85], 17 hydroxyprogesterone [0.5 +/- 0.2 vs. 0.7 +/- 0.2 microg/liter (1.6 +/- 0.6 vs. 2.0 +/- 0.6 nmol/liter); P = 0.63], and androstenedione [-1 +/- 12 vs. 8 +/- 11 ng/dl (-0.03 +/- 0.42 vs. 0.28 +/- 0.39 nmol/liter), P = 0.61] responses to hCG were not different between the groups. Cortisol responses were increased and dehydroepiandrosterone sulfate responses were decreased in the human immunodeficiency virus-infected vs. control subjects after ACTH stimulation. The ratio of DHEA to cortisol was significantly decreased at 60 (71 +/- 11 vs. 107 +/- 10; P = 0.02) and 90 (63 +/- 8 vs. 102 +/- 9; P = 0.004) min post-ACTH in the human immunodeficiency virus-infected patients compared with control subjects. Baseline urinary free cortisol levels were not different between the groups [36 +/- 9 vs. 36 +/- 5 microg/24 h (99 +/- 26 vs. 100 +/- 13 nmol/d)]. The DHEA to cortisol ratio correlated with the CD4 count (r = 0.67; P = 0.01). These data demonstrate significant shunting of adrenal steroid metabolism away from androgenic pathways and toward cortisol production in human immunodeficiency virus-infected women with the wasting syndrome. In contrast, our data suggest intact ovarian androgen responsivity to hCG stimulation. Further studies of the mechanism of adrenal steroid shunting and the efficacy of androgen replacement in human immunodeficiency virus-infected women are necessary.

Reduced bone density in androgen-deficient women with acquired immune deficiency syndrome wasting.

Women with acquired immune deficiency syndrome wasting are at an increased risk of osteopenia because of low weight, changes in body composition, and hormonal alterations. Although women comprise an increasing proportion of human immunodeficiency virus-infected patients, prior studies have not investigated bone loss in this expanding population of patients. In this study we investigated bone density, bone turnover, and hormonal parameters in 28 women with acquired immune deficiency syndrome wasting and relative androgen deficiency (defined as free testosterone < or =3.0 pg/ml, weight < or =90% ideal body weight, weight loss > or =10% from preillness maximum weight, or weight <100% ideal body weight with weight loss > or =5% from preillness maximum weight). Total body (1.04 +/- 0.08 vs. 1.10 +/- 0.07 g/cm2, human immunodeficiency virus-infected vs. control respectively; P < 0.01), anteroposterior lumbar spine (0.94 +/- 0.12 vs. 1.03 +/- 0.09 g/cm2; P = 0.005), lateral lumbar spine (0.71 +/- 0.14 vs. 0.79 +/- 0.09 g/cm2; P = 0.02), and hip (Ward's triangle; 0.68 +/- 0.14 vs. 0.76 +/- 0.12 g/cm2; P = 0.05) bone density were reduced in the human immunodeficiency virus-infected compared with control subjects. Serum N-telopeptide, a measure of bone resorption, was increased in human immunodeficiency virus-infected patients, compared with control subjects (14.6 +/- 5.8 vs. 11.3 +/- 3.8 nmol/liter bone collagen equivalents, human immunodeficiency virus-infected vs. control respectively; P = 0.03). Although body mass index was similar between the groups, muscle mass was significantly reduced in the human immunodeficiency virus-infected vs. control subjects (16 +/- 4 vs. 21 +/- 4 kg, human immunodeficiency virus-infected vs. control, respectively; P < 0.0001). In univariate regression analysis, muscle mass (r = 0.53; P = 0.004) and estrogen (r = 0.51; P = 0.008), but not free testosterone (r = -0.05, P = 0.81), were strongly associated with lumbar spine bone density in the human immunodeficiency virus-infected patients. The association between muscle mass and bone density remained significant, controlling for body mass index, hormonal status, and age (P = 0.048) in multivariate regression analysis. These data indicate that both hormonal and body composition factors contribute to reduced bone density in women with acquired immune deficiency syndrome wasting. Anabolic strategies to increase muscle mass may be useful to increase bone density among osteopenic women with acquired immune deficiency syndrome wasting.

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.

Effects of testosterone and progressive resistance training in eugonadal men with AIDS wasting. A randomized, controlled trial.

BACKGROUND: Substantial loss of muscle mass occurs among men with AIDS wasting. OBJECTIVE: To investigate the independent effects of testosterone therapy and progressive resistance training in eugonadal men with AIDS wasting. DESIGN: Randomized, controlled trial. SETTING: University hospital. PATIENTS: 54 eugonadal men with AIDS wasting (weight < 90% ideal body weight or weight loss > 10%). INTERVENTION: In a 2 x 2 factorial design, patients were assigned to receive testosterone enanthate (200 mg/wk) or placebo injections and progressive resistance training (three times weekly) or no training for 12 weeks. MEASUREMENTS: Cross-sectional muscle area and other indices of muscle mass. RESULTS: Cross-sectional muscle area increased in response to training compared with nontraining (change in arm muscle mass, 499 +/- 349 mm2 vs. 206 +/- 264 mm2 [P = 0.004]; change in leg muscle mass, 1106 +/- 854 mm2 vs. 523 +/- 872 mm2 [P = 0.045]) and in response to testosterone therapy compared with placebo (change in arm muscle mass, 512 +/- 371 mm2 vs. 194 +/- 215 mm2 [P< 0.001]; change in leg muscle mass, 1,236 +/- 881 mm2 vs. 399 +/- 729 mm2 [P = 0.002]). Levels of high-density lipoprotein cholesterol decreased in response to testosterone therapy compared with placebo (-0.03 +/- 0.13 mmol/L vs. 0.05 +/- 0.13 mmol/L [-1 +/- 5 mg/dL vs. 2 +/- 5 mg/dL]; P= 0.011) and increased in response to training compared with nontraining (0.05 +/- 0.13 mmol/L vs. 0.00 +/- 0.16 mmol/L [2 +/- 5 mg/dL vs. 0 +/- 6 mg/dL]; P = 0.052). CONCLUSIONS: In contrast to anabolic therapies that may have adverse effects on metabolic variables, supervised exercise effectively increases muscle mass and is associated with significant positive health benefits in eugonadal men with AIDS wasting.

Nutritional assessment of vitamin E in malnourished patients with AIDS.

Malnourished patients with acquired immunodeficiency syndrome (AIDS) may have low serum levels and reduced intake of alpha-tocopherol, mainly in the presence of acute-phase response. The aims of this study were to compare intake and serum levels of alpha-tocopherol between malnourished (MN) and non-malnourished (NMN) AIDS patients and to correlate alpha-tocopherol intake and serum levels. Undernutrition was defined as having a body mass index lower than 18. 5 kg/m(2) or a height-creatinine index lower than 70%. A semiquantitative food frequency questionnaire assessed alpha-tocopherol intake. High-performance liquid chromatography determined vitamin serum levels. The patients were divided into MN (n = 14) and NMN (n = 15) groups. There were no statistical differences in relation to clinical findings between MN and NMN, respectively, including moniliasis (7/14 versus 4/15), neurocryptoccocosis and neurotoxoplasmosis (6/14 versus 6/15), pulmonary tuberculosis (4/14 versus 2/15), and fever (1/14 versus 3/15). MN and NMN groups had similar peripheral blood CD(4) levels (111.4+/-87.1 versus 124.4+/-90.9 cells/mm(3)), and both groups had similar and adequate alpha-tocopherol intake (MN = 50.0+/-11.0 versus NMN = 47.2+/-16.5 mg) and serum levels (MN = 17.8+/-7.2 versus NMN = 19.8+/-6.3 micromol/L). Vitamin E intake and serum levels did not show a significant correlation (r = -0.22, P 0.05). Protein-energy nutrition status and acute-phase response were not factors determining vitamin status among AIDS patients.

Can androgen therapy replete lean body mass and improve muscle function in wasting associated with human immunodeficiency virus infection?

A significant number of men who are infected with the human immunodeficiency virus (HIV) have low testosterone levels. Androgen deficiency in HIV-infected patients is associated with decreased muscle mass and function, and adverse disease outcome. Administration of replacement doses of testosterone to healthy hypogonadal men augments lean body mass, muscle size, and maximal voluntary strength. Recent studies have shown that physiologic testosterone replacement in HIV-infected men with weight loss who have low testosterone levels can also increase muscle mass and effort-dependent strength. However, further studies are needed to determine whether androgen therapy can improve physical function and health-related outcomes in HIV-infected men.

Fasting hyperinsulinemia and increased waist-to-hip ratios in non-wasting individuals with AIDS.

OBJECTIVE: To identify metabolic and body composition changes associated with HIV-1 infection in a cross-sectional study of individuals stratified by immunologic status and body mass. DESIGN: Metabolic abnormalities including glucose intolerance and changes in body morphology have recently been described in HIV-1-infected individuals following therapy with protease inhibitor-containing highly active anti-retroviral therapy. Although this is suggestive of a direct drug effect, the possibility that HIV infection may induce a tendency towards such underlying derangements should be considered. HIV-infected patients are heterogeneous with respect to immunologic status and body mass. In examining the underlying effect of HIV-1 on metabolic and body composition parameters, stratification by various immunologic and body mass categories may give divergent results that would not be detected otherwise. METHODS: Thirty male participants were categorized into four cohorts: non-wasting HIV-seronegative controls, non-wasting HIV-infected patients with relatively intact immune function (CD4 cell count > 500 x 10(6)/l); non-wasting individuals with AIDS (CD4 cell count < 200 x 10(6)/l); and individuals with AIDS wasting. RESULTS: Increased fasting plasma insulin and waist-to-hip ratios were found specifically in non-wasting individuals with AIDS compared with HIV-negative controls. CONCLUSIONS: Our study emphasises the importance of both body mass and immune function in studying metabolic and body composition abnormalities associated with HIV-1 infection. The association of increased waist-to-hip ratios and hyperinsulinemia suggestive of insulin resistance in non-wasting individuals with AIDS suggest that the tendency towards these metabolic abnormalities may be related to the HIV infectious process or to factors associated with immunologic dysfunction.

Specific high-performance liquid chromatography assay for determination of rifabutin plasma concentration following Extrelut column extraction.

A specific, precise and accurate assay for determination of rifabutin in human plasma using Extrelut column extraction was developed and validated. Rifabutin concentrations were calculated with a standard curve ranging from 5 to 800 ng ml(-1). using a split-curve approach. Chromatographic peaks were separated by means of a 5 microm Symmetry Shield RP8 using a KH2PO4 (0.05 M) buffer-acetonitrile mobile phase. Detection wavelength was set at 275 nm. Chromatography was carried out at room temperature (20-25 degrees C). The limit of quantification was 5 ng ml(-1). The recovery was over 71%. The intra-day precision of the assay was 5, 7, and 1% while the inter-day precision was 11.2, 8.1, and 5.8% at concentrations of 30, 150 and 500 ng ml(-1), respectively. The accuracy ranged from 99 to 108%. Forty of the drugs most commonly administered to HIV-positive patients were found not to interfere with the assay. The assay has been used in a comparative study of rifabutin pharmacokinetics in HIV-positive patients with or without wasting syndrome. reserved.

Correlation between increased cortisol:DHEA ratio and malnutrition in HIV-positive men.

Malnutrition in HIV-infected patients is characterized by a loss of both fat-free mass (FFM) and fat mass (FM). Glucocorticoids and androgens change during the course of the infection and may play a key role in the protein balance. The serum concentrations of cortisol, adrenal (DHEA and DHEA sulfate) and gonadal androgens (androstenedione, testosterone, and dihydrotestosterone) of HIV-positive men were measured and compared with several parameters of body composition as a function of body weight loss (BWL). The patients were assigned to one of five groups according to their BWL: group I (controls, n = 10) < 5%, group II (n = 7) 5-10%, group III (n = 8) 10.1-16%, group IV (n = 9) 16.1-24%, and group V (n = 4) > 24.1%. Correlation analysis showed significant positive or negative relationships between several markers of malnutrition and adrenal androgens and the cortisol:DHEA ratio, but not with cortisol. BWL was negatively correlated with DHEA (r = -0.69, P < 0.0001), DHEA sulfate (r = -0.58, P < 0.0001) and testosterone (r = -0.34, P < 0.03), but positively with the cortisol:DHEA ratio (r = 0.61, P < 0.0001). In contrast, BCM was positively correlated with DHEA (r = 0.34, P < 0.04) and DHEA sulfate (r = 0.36, P < 0.03) and negatively with the cortisol:DHEA ratio (r = -0.58, P < 0.0001). The cortisol:DHEA ratio was also negatively correlated with BMI (body mass index) (r = -0.56, P < 0.01), fat-free mass (r = -0.48, P < 0.004), fat mass (r = -0.39, P < 0.02), and BCM:weight ratio (r = -0.47, P < 0.005) and positively with the extracellular:intracellular water ratio (r = 0.54, P < 0.001). These data indicate that the steroid hormone environment of patients, particularly their cortisol:DHEA ratio, is linked to the malnutrition associated with HIV infection. The decreased DHEA and increased cortisol in patients with the advanced stages of disease could be associated with increased protein catabolism.