The role of diet, exercise and smoking in dyslipidaemia in HIV-infected patients with lipodystrophy.

BACKGROUND: Lipodystrophy in HIV-infected (LDHIV) patients receiving protease inhibitors (PIs) is associated with dyslipidaemia. Whether lifestyle factors play a role in dyslipidaemia in LDHIV subjects on PIs is not well characterized. METHODS: A total of 45 LDHIV male and six LDHIV female patients on PIs were recruited, and data were collected on smoking, exercise, diet (by 3-day food record), and fasting levels of serum lipids and lipoproteins. The relationships between lifestyle factors and metabolic variables were analysed in male patients by Spearman's correlation test and the significant relationships were further analysed by adjusting for age, PI duration, and waist circumference by Spearman's partial correlation test. RESULTS: In men, mean (+/-standard deviation) serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and non-HDL-C were 212+/-70, 35+/-7.3, 325+/-230 and 169+/-44 mg/dL, respectively. Sixty-seven percent of the men exercised regularly and 31.1% smoked. The reported diet was high in cholesterol (390+/-212 mg) and percentage energy from saturated (12.2+/-3.3%) and trans (2.4+/-1.2%) fats, and low in soluble fibre (6.9+/-2.3 g) compared with recent dietary guidelines. Following adjustments for the confounding variables, percentage energy intake from total protein and animal protein was positively related to TC (r=0.44, P<0.01 and r=0.37, P<0.05, respectively), TG (r=0.40, P<0.01 and r=0.46, P<0.01, respectively) and non-HDL-C (r=0.56, P<0.001 and r=0.49, P<0.01, respectively), that from trans fat was positively related to TG (r=0.34, P<0.05), and soluble fibre was negatively related to non-HDL-C (r=-0.41, P<0.01). Moderate to heavy aerobic exercise tended to be associated with higher HDL-C (r=0.30, P=0.07) whereas smoking was not associated with any of the metabolic variables. CONCLUSIONS: Increased intake of total protein, animal protein and trans fat, and reduced soluble fibre consumption contribute to dyslipidaemia in LDHIV subjects on PIs.

HIV-1-specific CD4+ T cells are detectable in most individuals with active HIV-1 infection, but decline with prolonged viral suppression.

The role of HIV-1-specific CD4+ T-cell responses in controlling HIV-1 infection remains unclear. Previous work has suggested that such cells are eliminated in the early stages of infection in most subjects, and thus cannot substantially contribute to host defense against HIV-1. Here, using flow cytometric detection of antigen-induced intracellular cytokines, we show that significant frequencies of gag specific, T-helper-1 CD4+ memory T cells are detectable in most subjects with active/progressive HIV-1 infection (median frequency, 0.12% of memory subset; range, 0-0.66%). Median frequencies of these cells were considerably higher in nonprogressive HIV-1 disease (0.40%), but there was substantial overlap between the two groups (range of nonprogressors, 0.10-1.7%). Continuous HIV-1 suppression with anti-retroviral therapy was associated with a time-dependent reduction in median frequencies of gag-specific CD4+ memory T cells: 0.08% in subjects treated for 4-24 weeks, and 0.03% in subjects treated for 47-112 weeks. Thus, functional HIV-1-specific CD4+ T cells are commonly available for support of anti-HIV-1 effector responses in active disease, but their decline with anti-retroviral therapy indicates that immunologic participation in long-term HIV-1 control will probably require effective vaccination strategies.

A macromolecular inhibitor of in vitro calcification of tendon matrix.

Bovine and human tendon tissue do not induce calcification in vitro. However, extraction of those tissues with 3% Na2HPO4 converts them to calcifiable matrices. The supernatant fraction derived from the extraction contains a nondialyzable, perchloric acid soluble component that inhibits calcification of the extracted matrix. This inhibitory substance is characterized by a molecular weight in the range of 85,000-100,000. Exposure to pronase or hyaluronidase did not alter the inhibitory potency but did render the inhibitor dialyzable. Commercial sources of hyaluronic acid, chondrotitin-6-sulfate, chrondroitin-4-sulfate, dermatan sulfate, heparin and lysozyme did not inhibit calcification of the extracted matrix. Phosvitin, a phosphoglycoprotein is a potent inhibitor. Although phosvitin and the tendon extract also inhibit calcification of previously calcified matrix, they have no detectable effect on the rate of decalcification. We conclude that the mechanism of inhibition is characterized by a degree of specificity and that phosvitin and a macromolecular component of tendon tissue blocks conversion of an intermediate matrix-bound CaP complex to crystalline apatite. It seems reasonable that the tendon inhibitor could function in situ and possibly in vivo to control calcification of tendon tissue.