Pneumococcal meningitis during antiviral treatment with interferon and ribavirin in a splenectomized patient with chronic hepatitis C - do not miss vaccination before starting therapy.

We report on a 35-year-old man who developed pneumococcal meningitis while receiving antiviral therapy with interferon (consensus interferon, CIFN) and ribavirin for chronic hepatitis C. Antibiotic therapy was started four days after the onset of symptoms. Unfortunately, the patient developed a persisting right-sided cochlear hearing impairment. Antiviral therapy led to sustained viral response of hepatitis C. At the age of 14 years he had experienced a hemorrhagic shock after a traffic accident, received multiple blood transfusions and undergone a splenectomy. He had not received vaccination against Streptococcus pneumoniae. This case report reminds us that splenectomized patients without previous pneumococcal vaccination should receive such vaccination before immunomodulatory treatment.

ESPEN Guidelines on Enteral Nutrition: Wasting in HIV and other chronic infectious diseases.

Undernutrition (wasting) is still frequent in patients infected with the human immunodeficiency virus (HIV), despite recent decreases in the prevalence of undernutrition in western countries (as opposed to developing countries) due to the use of highly active antiretroviral treatment. Undernutrition has been shown to have a negative prognostic effect independently of immunodeficiency and viral load. These guidelines are intended to give evidence-based recommendations for the use of enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) in HIV-infected patients. They were developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. Nutritional therapy is indicated when significant weight loss (>5% in 3 months) or a significant loss of body cell mass (>5% in 3 months) has occurred, and should be considered when the body mass index (BMI) is <18.5 kg/m(2). If normal food intake including nutritional counselling and optimal use of ONS cannot achieve an adequate nutrient intake, TF with standard formulae is indicated. Due to conflicting results from studies investigating the impact of immune-modulating formulae, these are not generally recommended. The results obtained in HIV patients may be extrapolated to other chronic infectious diseases, in the absence of available data.

Acute phase response and energy balance in stable human immunodeficiency virus-infected patients: a doubly labeled water study.

We sought to assess possible associations of the acute phase response with energy balance as a cause of malnutrition in uncomplicated HIV-infection. Seven stable HIV-infected patients and 7 control subjects were followed for 2 weeks for blood chemistry, body composition, total and resting energy expenditure (TEE, REE), heart rate, energy intake, and physical activity; 6 patients were investigated for interleukin-2 receptor. TEE, REE, energy intake, and anthropometric data in patients and control subjects were very similar. However, physical activity, total body potassium, and bioimpedance phase angle were decreased (1.41 +/- 0.08 vs 1.55 +/- 0.9, 152 +/- 10 g vs 191 +/- 37 g, and 6.4 +/- 0.8 degrees vs 7.1 +/- 0.5 degrees; each P < .05), and mean heart rate, fibrinogen, and erythrocyte sedimentation rate were increased in HIV-infected patients (84 +/- 6 bpm vs 76 +/- 8 bpm, 4.3 +/- 1.2 g/L vs 2.5 +/- 0.4 g/L, and 21 +/- 13 mm vs 2 +/- 3 mm; P < .05). The deviation between the measured and the predicted REE in the patient group correlated positively with heart rate and serum interleukin-2 receptor concentrations (r = 0.83 and r = 0.91; P < .05). Possible increases in REE caused by an ongoing acute phase response may be counterbalanced by reduced physical activity that results in normal TEE in HIV infection.

Tumor necrosis factor, interleukin-6,and epinephrine are associated with hypermetabolism in AIDS patients with acute opportunistic infections.

During a 9-day period we investigated body composition, resting energy expenditure (REE), IL-6, TNF, and sTNFR-55 and sTNFR-75 plasma concentrations during infectious complications in 12 patients with HIV disease. At study entry, IL-6 was detectable in 5 and TNF in 10 patients. TNF was closely correlated with sTNFR-75 concentration (r = 0.84, p < 0.001) whereas sTNFR/sTNFR-55 ratio increased throughout the study. TNF concentrations were significantly correlated with the 24-hour excretion of epinephrine and norepinephrine (r = 0.64 and 0.69; each p < 0.01). Compared to expected values REE was increased by 34%. Body cell mass was the single best predictor of REE and explained 72% of its variance. In contrast, the deviation of measured from predicted REE was correlated with TNF and IL-6 concentrations (r = 0.9). We conclude that increased plasma concentrations of cytokines in complicated HIV disease display little biologic variability and relate to hypermetabolism in these patients.

Percutaneous endoscopic gastrostomy in AIDS and control patients: risks and outcome.

OBJECTIVES: Wasting is a major feature of advanced HIV infection. Enteral nutrition via percutaneous endoscopic gastrostomy (PEG) is a safe and efficient therapy in malnutrition, but limited experience exists in wasted HIV patients. Here we report on outcome and risk of PEG-feeding in HIV patients compared with HIV-seronegative patients and with HIV patients without PEG. METHODS: In 47 HIV-infected patients, PEG was placed because of wasting (n = 33), neurologic deficits (n = 11), or dysphagia (n = 3). Clinical, immunological, and nutritional data were compared with those of i) 15 HIV patients who refused PEG placement despite an appropriate indication, ii) 76 HIV patients without signs of malnutrition, and iii) 43 miscellaneous PEG patients. RESULTS: PEG was as safe in HIV-infected as in HIV-seronegative patients. PEG feeding resulted in significant increases of body weight (+3.3 +/- 3.6 kg, p < 0.001), serum albumin concentration (+4.5 +/- 7.2 g/L, p < 0.005), and total iron-binding capacity (+9.5 +/- 11.5 mumol/L, p < 0.001). Moreover, our data indicate that PEG feeding may improve survival in wasted AIDS patients. CONCLUSIONS: PEG feeding is safe and effective in the treatment of the AIDS wasting syndrome. Further prospective investigations are necessary to answer the question of whether treatment of wasting improves patient survival.

Weight gain and increased concentrations of receptor proteins for tumor necrosis factor after patients with symptomatic HIV infection received fortified nutrition support.

OBJECTIVE: To determine whether certain nutrients and dietary factors act as modulators of the immune system and improve the nutritional status of immunocompromised patients. DESIGN: Controlled, double-blind, crossover phase trials of the effects of a fortified formula in patients infected with the human immunodeficiency virus (HIV). Patients consumed a control formula for 4 months and a study formula for 4 months. SUBJECTS: Ten men with symptomatic HIV infection who were following stable medication regimens and had no malignancies, mycobacteriosis, or additional virus infection requiring systemic treatment. INTERVENTION: Formula fortified with alpha-linolenic acid (1.8 g/day), arginine (7.8 g/day), and RNA (0.75 g/day) and a standard formula. MAIN OUTCOME MEASURES: Nutritional status determined by anthropometric, bioelectrical, biochemical, and dietary assessment; energy expenditure determined by indirect calorimetry; disease progression; CD4 lymphocyte counts; HIV p24 antigen plasma concentrations; tumor necrosis factor (TNF) receptor proteins; and compliance control parameters. STATISTICAL ANALYSES PERFORMED: Student's t tests for paired and unpaired data. RESULTS: Fortified nutrition resulted in a weight gain (+ 2.9 kg/4 months vs -0.5 kg/4 months with the control formula, P < .05), an incorporation of eicosaenoic acid into erythrocyte cell membranes (+ 47% of baseline values, P < .05), and increased plasma arginine concentrations (96.8 +/- 45.1 vs 51.8 +/- 20.9 mumol/L, P < .01). The serum concentrations of the soluble tumor necrosis factor receptor (sTNFR) proteins increased during the study period (sTNFR 55 = + 0.23 vs -0.40 ng/mL, P < .001; sTNFR 75 = + 0.90 vs -0.36 ng/mL, P < .01), whereas no changes in CD4+ lymphocyte counts were observed. CONCLUSION: Increasing dietary intakes of n-3 polyunsaturated fatty acids, L-arginine, and RNA increased body weight, possibly by modulating the negative effects of TNF.

Ketotifen in HIV-infected patients: effects on body weight and release of TNF-alpha.

OBJECTIVE: Tumor necrosis factor alpha (TNF-alpha) is involved in the genesis of HIV-associated malnutrition. We performed an open-label trial on the effects of ketotifen, an in vitro inhibitor of TNF-alpha release from peripheral blood mononuclear cells (PBMCs), on the nutritional status and TNF-alpha release of HIV-infected subjects. PATIENTS: Six HIV-infected subjects received oral ketotifen 4 mg per day for 84 days and were followed up for an additional 70-day period. Body composition was measured by bioelectrical impedance analysis. TNF-alpha plasma levels, TNF-alpha release from PBMCs, and plasma concentration of soluble TNF receptors were measured repeatedly during the study and control period. RESULTS: During ketotifen intake, TNF-alpha release from stimulated PBMCs significantly decreased (68 vs 155 pg ml-1), but not TNF-alpha and soluble TNF receptor plasma concentrations. Subjects gained weight (+ 2.7 kg), whereas weight loss was observed after cessation of treatment (-1.6 kg). CONCLUSION: Ketotifen inhibits TNF-alpha release from stimulated PBMCs and might thus be useful in the management of HIV-associated malnutrition.

Effect of increased protein intake and nutritional status on whole-body protein metabolism of AIDS patients with weight loss.

The aim of this study was to investigate nutritional status and protein metabolism during total parenteral nutrition (TPN) in AIDS patients with weight loss. Six patients on treatment for AIDS-associated complications were investigated and reviewed TPN that supplied energy equivalent to 1.5 times the resting energy expenditure (REE). Amino acid (AA) supply increased from 0.6 g/kg body weight (BW)/d on days 1 to 3 and 1.2 on days 4 to 6 to 1.8 on days 7 to 9. Nonprotein energy was given as equicaloric amounts of glucose and fat emulsion. There were repeated measurements of nitrogen balance and whole-body protein turnover (WBPT) using a bolus 15N-glycine method on the morning of days 3, 6, and 9. Principal findings were as follows: (1) increasing the supply of AAs significantly improves nitrogen balance in AIDS patients; (2) there is no simple linear effect of increasing amounts of AAs on WBPT in AIDS patients; (3) WBPT is high and variable in these patients; and (4) mean WBPT of each patient is significantly correlated with body cell mass (BCM) as a proportion of BW (P < .001, r = .92). We conclude that poor nutritional status in AIDS patients with weight loss is associated with high WBPT. However, these patients can attain at least transiently positive nitrogen balance with sufficient protein intake, predominantly through an increase in whole-body protein synthesis (WBPS).

[Diet therapy of immunocompromised patients as exemplified in HIV-infection]. / Ernährungstherapie des immungeschwächten Patienten am Beispiel der HIV-Infektion.

Presently, there is no special nutrition for HIV-infected patients; however, there exist preliminary data suggesting that immunonutrition may have benefits in patients with AIDS. Nutritional assessment and nutritional counseling are mandatory in every patient with HIV infection. Both strategies are part of supportive care and should be done as early as possible during the course of the disease. There is evidence that improving the nutritional state will also improve the prognosis of the patients.

Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected outpatients.

Although malnutrition and wasting are known features of human immunodeficiency virus (HIV) infection, their incidence and possible association with immunologic impairment are largely unknown, as is the prognostic value of the nutritional state. Nutritional, clinical, and immunologic parameters were measured in 100 outpatients in different stages of HIV infection. In addition, 39 patients with AIDS were prospectively followed for a mean period of 343 (range, 53-650) days. Sixty-three percent of the patients showed evidence of malnutrition, 21% suffered from wasting. A reduced body cell mass and decreased serum albumin levels were observed in 32 and 14%, respectively, predominantly in more advanced disease stages. Fourteen of 39 AIDS patients died after a mean survival of 212 days. Survivors showed significantly larger initial body cell mass values and higher initial serum albumin levels compared with nonsurvivors, whereas CD4+ lymphocyte counts, disease complications, and medication were all similar in both groups. Kaplan-Meier analyses revealed a significantly prolonged survival in patients with a body cell mass > 30% of body weight or serum albumin levels exceeding 30 g/L. Factor analyses indicated that the parameters of nutritional state were independent from each other and from CD4+ lymphocyte counts. Malnutrition occurs frequently during HIV infection and increases with disease progress. It strongly predicts patient survival independent of CD4+ lymphocyte counts.

Tumour necrosis factor receptor levels are linked to the acute-phase response and malnutrition in human-immunodeficiency-virus-infected patients.

1. Increased release of tumour necrosis factor is thought to contribute to human-immunodeficiency-virus-associated wasting syndrome. Elevated serum concentrations of tumour necrosis factor have, however, mainly been found during acute opportunistic infections and were not correlated with the degree of wasting. This finding may be explained by the paracrine release and the rapid inactivation of tumour necrosis factor. Serum levels of the two recently detected soluble tumour necrosis factor receptor proteins (p55 and p75) are assumed to reflect tumour necrosis factor release. 2. Serum levels of soluble tumour necrosis factor receptors 55 and 75 were measured by an enzyme-linked immunological and biological binding assay in 45 human-immunodeficiency-virus-infected patients and seven healthy control subjects. Patients were followed up for survival. Serum albumin, prealbumin, total iron-binding capacity (transferrin) and C-reactive protein concentrations were measured using standard laboratory methods. Body composition was determined by bioelectrical impedance analysis. 3. Serum concentrations of soluble tumour necrosis factor receptor 55 and 75 were both significantly increased in human-immunodeficiency-virus-infected patients as compared with the health control subjects (P < 0.05); soluble tumour necrosis factor receptor concentrations were even more increased in patients with elevated C-reactive protein levels (> or = 5mg/l) as compared with those with normal C-reactive protein levels (< 5mg/l; P < 0.0001 and P < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Home enteral nutrition in patients with Acquired Immunodeficiency Syndrome.

UNLABELLED: 14 patients in advanced stages of HIV infection (1 ARC, 13 AIDS; sex: 1 female, 13 male; age 37.8 +/- 6.3 years; body mass index (BMI): 17.4 +/- 2.4 kg/m(2)) were followed prospectively while receiving home enteral nutrition (observation period: 62 +/- 75 days). Artificial nutrition was indicated because of severe weight loss (9-38 kg within 6-48 months, n = 7) or cerebral toxoplasmosis with eating and swallowing disorders (n = 7). In all patients a defined formula diet (175 +/- 17.7 kJ/kg body weight) was administered through an endoscopically placed gastrostomy tube (PEG). Home enteral nutrition was well tolerated by all patients and no significant PEG-related complications occurred. Enteral nutrition resulted in significant increases in body weight (p < 0.005), body cell mass (BCM, p < 0.05), total body fat (TBF, p < 0.005), serum albumin concentration (p < 0.05), and serum total iron-binding capacity (transferrin, p < 0.01). CONCLUSION: Home enteral nutrition via PEG is safe and well tolerated in patients with advanced HIV-related immunodeficiency and is capable of improving nutritional state including BCM.

Resting energy expenditure and weight loss in human immunodeficiency virus-infected patients.

Resting energy expenditure (REE) and body composition were investigated in 60 clinically stable patients with human immunodeficiency virus (HIV) infection varying with respect to immune impairment. REEs differed significantly from predicted values (> or < 10% of the Harris-Benedict [HB] equation) in 40% of patients. Seven percent of patients showed markedly increased REE (> +20% of HB prediction), whereas REE was decreased in 13% (< -10%). Increased REE was found during all clinical stages of the disease (Walter Reed [WR] 2 through 6) and was not strictly associated with the degree of immune impairment, presence of diarrhea or Kaposi's sarcoma, nutritional state, or anamnestic wasting. Twenty-seven patients were evaluated for a mean period of 319 days; 11 lost more than 5% of their initial body weight during the observation period. Weight-losing patients were normometabolic before but showed a significantly increased REE (+7% of predicted values or +8% when compared with previous measurements) during weight loss. The degree of deviation from estimated REE was strongly associated with the degree of weight loss. We summarize that increased REE is not a constant feature of HIV infection. It is not associated with clinical and laboratory parameters of immune deficiency, but may occur during weight loss. Thus increased REE represents an inadequate adaptation to malnutrition and contributes to wasting.

Malnutrition and immune dysfunction in patients infected with human immunodeficiency virus.

STUDY OBJECTIVE: To determine forms of malnutrition and basal metabolism at different stages of immunological impairment in clinically stable patients infected with Human Immunodeficiency Virus (HIV). DESIGN: Cross sectional study. SETTING: 53 outpatients with HIV-infection classified according to the Walter Reed staging system (WR1 to WR6). MEASUREMENTS AND MAIN RESULTS: 87% of the patients showed some evidence of malnutrition. Reduced body weight was found in 53%, 68% and 25% had decreases in fat and body cell mass, 17% had visceral protein deficiency, whereas extracellular mass and serum triglyceride concentrations were increased in 58% and 30%, respectively. Reduced serum albumin and transferrin closely paralleled immunological depression, whereas alterations in body composition were manifest early during HIV-infection (WR3) and remained unchanged during the transition to the Acquired Immune Deficiency Syndrome itself. Resting metabolic rate increased from WR1 to WR3; it remained within the expected range during later stages (WR4-WR6), but was not appropriately reduced in response to the loss in body cell mass. CONCLUSIONS: HIV-infected patients display both, calorie and protein malnutrition. Immunological depression was independent of loss of body mass, but was closely associated to decreases in serum albumin values. Nutritional assessment and intervention should therefore be performed at an early stage of HIV-infection.

Cytomegalovirus infection in HIV-1-infected individuals.

Urinary excretion of Cytomegalovirus and the presence of serum antibodies against CMV were examined in 79 HIV-1-infected patients at different stages of the disease, as well as in 27 heterosexual and 52 male homosexual controls and correlated to clinical and laboratory results. HIV-1-infected and healthy individuals differed significantly with regard to cutaneous delayed type reactions, absolute numbers of CD4+ cells and CD4+/CD8+ ratios. IgG antibodies against CMV were found in 87% of homosexual and in 52% of heterosexual controls, and in all HIV-1-infected homosexuals. CMV excretion in the urine was exclusively found in HIV-1-infected individuals where the incidence correlated with the CDC-defined disease stage (stage II: 6%, stage III/IV A: 22%, stage IV B/C: 55%). HIV-1-infected patients excreting CMV in the urine also exhibited distinctly decreased numbers of CD4+ cells and significantly decreased CD4+/CD8+ ratios compared to those without CMV viruria.