The metabolic response to opportunistic infections in AIDS.

OBJECTIVE: The metabolic response to AIDS-defining opportunistic infections was examined to provide a logical basis for the management of associated weight loss. DESIGN: A prospective study of metabolism in AIDS. SETTING: HIV outpatients' department and wards at the Chelsea and Westminster Hospital, London. PATIENTS: Ten asymptomatic Centers for Disease Control and Prevention stage II HIV-seropositive control subjects and 36 HIV-seropositive patients with a single newly diagnosed and untreated opportunistic infection [10 with microsporidial or cryptosporidial diarrhoea, 10 with Pneumocystis carinii pneumonia, nine with cytomegalovirus enteritis and seven with systemic Mycobacterium avium-intracellulare]. MAIN OUTCOME MEASUREMENTS: Subjects had measurements of resting energy expenditure using indirect calorimetry and of body composition using dual energy X-ray absorptiometry. RESULTS: Subjects with protozoal diarrhoea had a decreased resting energy expenditure (P < 0.05) and decreased body fat (P < 0.01). Subjects with P. carinii pneumonia had an elevated resting energy expenditure (P < 0.05). Subjects with systemic M. avium-intracellulare had an elevated resting energy expenditure (P < 0.05) and decreased skeletal muscle mass (P < 0.05). Subjects with cytomegalovirus enteritis had a non-significant elevation of resting energy expenditure with a non-significant loss of both fat and lean tissue. CONCLUSION: Subjects with protozoal diarrhoea show a starvation response to infection and subjects with systemic M. avium-intracellulare show a cachectic response. Since there is a variation in the metabolic response to opportunistic infection in AIDS patients, nutritional management should be directed according to the specific cause.

Faecal tumour necrosis factor-alpha in individuals with HIV-related diarrhoea.

OBJECTIVE: HIV-related gastrointestinal infection is associated with diarrhoea, weight loss, mucosal inflammation and increased intestinal permeability. As tumour necrosis factor (TNF)-alpha may mediate these features this cytokine was measured in the faeces of HIV-seropositive individuals with diarrhoea to assess its role in the pathogenesis of HIV-related gastrointestinal disease and the association with specific intestinal pathogens. DESIGN: Prospective study. METHODS: Two hundred and four HIV-seropositive individuals provided stool samples that were analysed for faecal TNF-alpha (FTNF-alpha) using a standard sandwich enzyme-linked immunosorbent assay. RESULTS: Stool from patients with bacterial, cytomegalovirus (CMV) and microsporidial diarrhoea had significantly elevated FTNF-alpha compared with those who had pathogen-negative diarrhoea (P < 0.05). FTNF-alpha was not raised in cryptosporidiosis, pathogen-negative or solid stool. In subjects with diarrhoea of more than 2 weeks duration and three stool samples negative for enteric pathogens, FTNF-alpha greater than 15 U/ml has a sensitivity of 88% and a specificity of 66% for the diagnosis of diarrhoea-related CMV enteritis. CONCLUSION: TNF-alpha production may have a role in the pathogenesis of bacterial, microsporidial and CMV-related diarrhoea in HIV-seropositive individuals. Thus, anti-TNF-alpha agents may have a therapeutic role in the management of these conditions. FTNF-alpha greater than 15 U/ml in apparently pathogen-negative diarrhoea may suggest endoscopic gastrointestinal biopsy to diagnose CMV enteritis.

Energy balance in asymptomatic HIV infection.

OBJECTIVES: Body weight is regulated by the balance between energy intake and energy expenditure, but the influence of HIV infection on energy balance has not been fully examined. The main objectives of this study were (1) to assess the effect of HIV on energy balance, (2) to examine the relationship of parameters of immunodeficiency to energy balance, and (3) to examine the interrelationship of different components of energy balance in asymptomatic HIV-seropositive men. DESIGN: A cross-sectional study of nutrition and metabolism in asymptomatic HIV-seropositive men METHODS: Components of energy balance were examined in 104 asymptomatic HIV-seropositive men (CD4 count 4-482 x 10(6)/l) and 57 age-matched HIV-seronegative male controls. Energy and protein intake were measured using 5-day diaries, and small bowel absorption and permeability was assessed using four sugar probes. Resting energy expenditure was calculated from indirect calorimetry and nitrogen loss estimated from 24 h urine collection. Four methods were used to assess the effect of HIV infection on body composition (anthropometry, dual energy X-ray absorptiometry, bioelectrical impedance and 24 h urine creatinine). RESULTS: Resting energy expenditure per kilogram of fat-free mass was raised (P < 0.0001), fat mass was decreased (P = 0.001), fat-free mass was increased (P = 0.05), energy intake was higher (P = 0.05), absorption of L-rhamnose (P = 0.01) and 3-O-methyl-D-glucose was decreased (P = 0.003), and small bowel permeability was increased (P < 0.0001) in HIV-seropositive men compared with HIV-seronegative controls. HIV-seropositive subjects with a CD4 count less than 100 x 10(6)/l had decreased absorption of L-rhamnose (P < 0.05), D-xylose (P < 0.05) and 3-O-methyl-D glucose (P < 0.05) compared with HIV-seropositive subjects at higher CD4 counts, and had a similar resting energy expenditure to HIV-seronegative controls. Protein intake, carbohydrate, fat and protein oxidation. 24 h nitrogen excretion and appendicular muscle mass were similar in HIV-seropositive men and controls. CONCLUSION: HIV infection exerts a direct effect on parameters of energy balance that varies with the severity of immunosuppression.

Intestinal inflammation, ileal structure and function in HIV.

OBJECTIVES: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals. METHODS: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy. RESULTS: Well, HIV-infected, subjects had normal intestinal absorption-permeability, but both functions were impaired upon the development of AIDS. The median faecal excretion of 111indium in well patients (0.66%) did not differ significantly (P > 0.5) from controls (0.46%), but subjects with AIDS who were well or who had diarrhoea had significant (P < 0.005) intestinal inflammation (1.33% and 2.18%, respectively). The median 7-day retention of tauro 23-[75Se]-selena 25-homocholic acid in well patients with AIDS (38.9%) did not differ significantly (P > 0.2) from controls (39.3%), whereas the absorption of 58cobalt-labelled cyanocobalamine was significantly (P < 0.05) lower than controls (32.1% and 59.4%). Patients with AIDS-diarrhoea had significant (P < 0.001) malabsorption of both the bile acid (7.7%) and vitamin B12 (8.9%) which was more severe than in Crohn's ileitis (14.2% and 30.3%, respectively). Morphometric analyses of ileal biopsies were unremarkable in AIDS. CONCLUSIONS: These studies demonstrate a low-grade enteropathy in patients with AIDS, severe ileal malabsorption in patients with AIDS diarrhoea and relatively minor ileal morphologic changes. Malabsorption of bile acids may play a pathogenic role in patients with AIDS and diarrhoea.

Short-term growth hormone administration at the time of opportunistic infections in HIV-positive patients.

OBJECTIVES: A 12-week course of recombinant human growth hormone is an effective but expensive therapy for established HIV-related wasting. Wasting in HIV disease is often episodic, coinciding with bouts of acute opportunistic infection. We hypothesized that a short course of growth hormone, targeted at the time of opportunistic infection, might improve protein metabolism thereby reducing lean tissue loss. METHODS: HIV-infected men with acute opportunistic infections, who received standard antimicrobial treatment for their infection as well as intensive nutritional counselling and oral energy supplements, were randomized to receive growth hormone or placebo for 14 days. Principal assessments were protein metabolism (measured by 13C-leucine infusion), body composition (measured by DEXA) and safety. RESULTS: There were no significant changes in outcome parameters in the placebo group (n = 11). In the growth hormone group (n = 9), protein catabolic rate decreased by 60% in the fasted state (P = 0.02 versus placebo), lean body mass increased by 2.2 kg (P = 0.03 versus baseline) and fat mass decreased by 0.7 kg (P = 0.002 versus baseline). There was no increase in adverse or serious adverse events in the growth hormone as compared with the placebo group. CONCLUSIONS: A two-week course of growth hormone at the time of acute opportunistic infection in HIV-infected patients improves protein metabolism and body composition during therapy and appears to be safe. This may represent a rational and economical approach to the use of growth hormone therapy.

Inflammatory bowel disease in individuals seropositive for the human immunodeficiency virus.

OBJECTIVE: CD4 lymphocytes mediate disease expression in both human immunodeficiency virus (HIV) infection and inflammatory bowel disease (IBD). Analysis of the clinical course of IBD in HIV-seropositive individuals may elucidate aspects of the role of CD4 lymphocytes in the pathogenesis of these conditions. DESIGN: A retrospective case series study. PATIENTS: Diagnostic coding for IBD and pharmacy records for 5-aminosalicylic acid compounds and rectal steroid preparations were examined for all HIV-seropositive subjects attending the Chelsea and Westminster Hospitals between January 1988 and December 1993. Eight HIV-seropositive individuals with a confirmed diagnosis of IBD were identified. SETTING: HIV/Genitourinary medicine (GUM) units. MAIN OUTCOME MEASURES: Change in CD4 count. RESULTS: Four subjects with an intact colon had a decline in CD4 count of 85 cells/mm3/year, four patients undergoing colectomy had a subsequent rise of four cells/mm3/year and eight case matched controls had a decline of 47 cells/mm3/year. Acute exacerbations of IBD did not cause a significant change in CD4 count. There were no exacerbations of IBD in patients with a CD4 count below 200 cells/mm3. CONCLUSION: HIV infection may influence the pathogenesis of IBD. A chronically inflamed colon may accelerate CD4 cell depletion which is reversed by colectomy.