Increased abdominal visceral fat is associated with reduced bone density in HIV-infected men with lipodystrophy.

OBJECTIVE: To examine the relationship between bone density and changes in regional and whole body composition in HIV-infected men with and without lipodystrophy. DESIGN: Cross-sectional, observational study of HIV-infected men with and without lipodystrophy and matched HIV-negative controls. SETTING: Tertiary care academic medical institution. PATIENTS: A total of 59 men, belonging to three different groups: HIV-positive men with lipodystrophy (n = 21), HIV-positive men without lipodystrophy (n = 20), and age-matched and body mass index-matched HIV-negative controls (n = 18). METHODS: Bone density, markers of bone turnover and indices of calcium metabolism were measured in all subjects. Quantitative computed tomography was used both to determine volumetric bone density of the spine and to quantify abdominal visceral fat. Dual energy X-ray absorptiometry was used to determine whole body composition and bone density. Statistical comparisons were performed according to lipodystrophy categorization and protease inhibitor exposure. RESULTS: Men with HIV-associated lipodystrophy had reduced lumbar spine bone density compared with both HIV-infected non-lipodystrophic men [mean +/- SD, 132 +/- 29 versus 154 +/- 30 mg/cm(3); P = 0.02] and HIV-negative controls [mean +/- SD 132 +/- 29 versus 148 +/- 18) mg/cm(3); P = 0.04]. Lumbar spine bone density was reduced significantly in HIV lipodystrophy patients independently of protease inhibitor use. In an analysis among all HIV-infected subjects, increased visceral abdominal fat area was associated with decreased lumbar spine bone density (r, -0.47; P = 0.002). The association between visceral fat and bone density remained significant (P = 0.007) after controlling for age, body mass index, lowest body weight, protease inhibitor use, and extremity fat in a multivariate regression model. Markers of bone turnover were not related to bone density or lipodystrophy status. CONCLUSIONS: Lumbar spine bone density is reduced in association with increased visceral fat in HIV-infected men with lipodystrophy. Further studies are needed to determine the mechanisms of osteopenia in HIV lipodystrophy and whether increased marrow fat occurs in such patients and affects bone density.

Assessment of growth hormone dynamics in human immunodeficiency virus-related lipodystrophy.

Human immunodeficiency virus (HIV) lipodystrophy (LIPO) is characterized by increased visceral adiposity, peripheral fat atrophy, dyslipidemia, and insulin resistance. GH concentrations are known to vary inversely with excess weight and body fat but have not been investigated in HIV lipodystrophy. Twenty-one subjects with HIV LIPO, 20 HIV-infected nonlipodystrophy subjects (NONLIPO), and 20 control (C) subjects were prospectively recruited for this study and compared. Subjects in the three groups were all male, age-matched [median, 47 yr old (interquartile range, 37-50) LIPO; 41 (37-44) NONLIPO; and 43 (37-49) C], and body mass index-matched [median, 24.3 kg/m(2) (interquartile range, 22.2-26.6) LIPO; 24.4 (23.3-25.9) NONLIPO; and 24.8 (22.7-26.1) C] (P: > 0.05 for all comparisons). Visceral abdominal fat [16,124 mm(2) (11,246-19,790) LIPO; 7,559 (5,134-11,201) NONLIPO; and 8,803 (6,165-11,623) C; P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] and the ratio of visceral abdominal fat to sc abdominal fat [1.37 (0.71-2.44) LIPO vs. 0.57 (0.47-0.78) NONLIPO vs. 0.55 (0.41-0.71) C, P < 0.01 LIPO vs. NONLIPO and LIPO vs. C] were significantly increased in the LIPO subjects but were not significantly different between NONLIPO and C. The mean overnight GH concentration, determined from frequent sampling every 20 min (from 2000 h to 0800 h) was decreased in the LIPO subjects [0.38 microg/L (0.13-0.67) LIPO vs. 0.96 (0.53-1.30) NONLIPO vs. 0.81 (0.49-1.03) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and not significantly different between NONLIPO and C. Pulse analysis demonstrated decreased baseline GH [0.08 microg/L (0.06-0.21) LIPO vs. 0.19 (0.10-0.32) NONLIPO vs. 0.17 (0.12-0.57) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] and GH peak amplitude [1.06 microg/L (0.46-1.94) LIPO vs. 2.47 (1.22-3.43) NONLIPO and 2.27 (1.36-4.25) C, P < 0.05 LIPO vs. NONLIPO and LIPO vs. C] in the LIPO subjects but no significant difference in pulse frequency. No significant differences were observed between NONLIPO and C for any GH parameter. Insulin-like growth factor-I was not different between the groups. Total body fat (r = -0.40, P = 0.01) and visceral fat (r = -0.58, P = 0.0001) correlated inversely with mean overnight GH concentrations in the HIV-infected patients. In a multivariate regression model, controlling for age, body mass index, body fat, and visceral fat, only visceral fat was a significant predictor of mean GH concentrations (P = 0.0036, r(2) for model = 0.40). These data demonstrate normal GH pulse frequency and insulin-like growth factor-I concentrations but reduced mean GH concentrations, basal GH concentrations, and GH pulse amplitude in patients with HIV lipodystrophy. Increased visceral adiposity is the strongest predictor of reduced GH concentrations in HIV lipodystrophy. Further studies are necessary to determine the clinical significance of reduced GH in patients with HIV lipodystrophy.

Metabolic abnormalities and cardiovascular disease risk factors in adults with human immunodeficiency virus infection and lipodystrophy.

We evaluated metabolic and clinical features of 71 HIV-infected patients with lipodystrophy by comparing them with 213 healthy control subjects, matched for age and body mass index, from the Framingham Offspring Study. Thirty HIV-infected patients without fat redistribution were compared separately with 90 matched control subjects from the Framingham Offspring Study. Fasting glucose, insulin, and lipid levels; glucose and insulin response to standard oral glucose challenge; and anthropometric measurements were determined. HIV-infected patients with lipodystrophy demonstrated significantly increased waist-to-hip ratios, fasting insulin levels, and diastolic blood pressure compared with controls. Patients with lipodystrophy were more likely to have impaired glucose tolerance, diabetes, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol than were controls. With the exception of HDL cholesterol level, these risk factors for cardiovascular disease (CVD) were markedly attenuated in patients without lipodystrophy and were not significantly different in comparison with controls. These data demonstrate a metabolic syndrome characterized by profound insulin resistance and hyperlipidemia. CVD risk factors are markedly elevated in HIV-infected patients with fat redistribution.

Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy.

Previous studies have indicated that there is a significant prevalence (50%) of hypogonadism among men with acquired immunodeficiency syndrome (AIDS)-associated wasting, and for these patients testosterone administration has been shown to increase lean body mass and improve quality of life. However, the prevalence of hypogonadism is not known among men with weight loss related to human immunodeficiency virus (HIV) infection who are receiving highly active antiretroviral therapy (HAART). From 1997 through 1999, we investigated total and free testosterone levels in 90 men who were <90% of ideal body weight or had weight loss of >10% from preillness weight; 71% of these subjects were receiving HAART. Twenty-one percent of the subjects receiving HAART had low free testosterone levels. No correlation was seen between weight, CD4 cell count, medication status, and other clinical factors. These data suggest that hypogonadism remains relatively common in men with AIDS wasting, despite treatment with HAART. HIV-infected men with wasting syndrome should be screened for hypogonadism and receive physiological androgen replacement therapy if they are hypogonadal.

The use of ketoconazole in prophylaxis of Candida sepsis.

Candida sepsis has become an increasing problem in ICU patients with up to 50 per cent mortality rate. Ketoconazole, an oral antifungal agent, was used prophylactically in guinea pigs to see if this would prevent Candida sepsis. Absorption of ketoconazole has been stated to increase in an acid environment. Thirty-six guinea pigs were divided into three equal groups: group I received 1 cc normal saline, p.o.; group II received 10 mg/kg ketoconazole dissolved in 1 ml Maalox (Rorer Consumer; Fort Washington, PA); group III received 10 mg/kg ketoconazole in 1 ml in HCl, all given daily. Each animal received 10(8) colony forming units intravenously. The viability of the innoculum was confirmed by culture both pre- and postinjection. Each animal was observed daily for weight and ocular and skin lesions. Half of the animals were sacrificed on day seven and the remaining were sacrificed on day 14. Cultures, complete blood count (CBC), ketoconazole levels, and specimen histology were obtained. There was no difference between groups as to weight, leukocyte counts, skin or ocular lesions, or ketoconazole levels. Histologic analysis and quantitative cultures revealed little Candida invasion. In conclusion, Candida sepsis cannot be induced in healthy guinea pigs. The blood levels of ketoconazole were not affected by pH.