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.

Effect of interferon alpha on high serum androgen concentrations in HIV positive men with Kaposi's sarcoma.

AIM: To measure serum androgen concentrations in men with HIV related Kaposi's sarcoma (KS) who had been treated with recombinant interferon (IFN) alpha-2a to determine the role of androgens on the development of KS lesions. METHODS: 32 men with HIV related KS who had been treated with IFN were studied: 24 men in complete KS remission and eight not in remission. Serum androgen concentrations were determined before, during, and after IFN treatment and correlated with clinical remission. RESULTS: All patients in complete KS remission had lower serum androgen concentrations following IFN treatment: -51% for dehydroepiandrosterone (DHEA) (p < 0.0001); -38% for DHEA sulphate (p < 0.002);-39% for androstenedione (p < 0.002); and -44% for testosterone (p < 0.007). These decreases brought the serum concentrations to about normal levels. However, IFN had varying effects on serum androgen concentrations in the men not in remission: a small decrease, a large increase in one androgen, or no change in serum androgens. CONCLUSIONS: The association between serum androgen levels and the progression or remission of HIV associated KS suggests that androgens affect the development of KS lesions. A clear understanding of the changes in the androgen environment may provide a sound basis for the development of new therapeutic strategies.

Serum cortisol and DHEA concentrations during HIV infection.

The progression of HIV infection is accompanied by severe immunodepression and cachexia, particularly during advanced stages. The immune depression is due largely to a dramatic drop in the number of CD4 cells. The loss of body weight is mainly due to a reduced fat-free mass with no change in adipose tissue. We determined the serum concentrations of cortisol and DHEA and their correlations with absolute CD4 cell counts and changes in body weight of HIV-positive men. The results of five retrospective and prospective studies indicate that the serum concentrations of cortisol and DHEA in HIV-infected patients were different from those of HIV-negative controls. Serum cortisol was elevated at all stages of infection (+20 to +50%, p < .05 to p < .001) particularly in AIDS patients (stage IV C). In contrast, the serum DHEA concentrations were closely correlated with the stage of HIV-infection, being higher in the early stages (stages II and III or > 500 CD4) than in advanced stages (IV C or < 500 CD4)-in the latter being below those of HIV-negative men-or in controls (+40 to 100%, p < .01 to p < .001). There was a negative linear correlation between the CD4 cell counts and cortisol (r = -0.4, p < .02) and a positive linear correlation with DHEA (r = +0.36, p < .01). There was no significant correlation between delta body weight and serum cortisol. In contrast, there was a negative correlation between serum DHEA and delta body weight (%) (r = -0.69, p < .0001) and a positive correlation with the cortisol/DHEA ratio (r = +0.61, p < .0001). There is thus a link between the circulating concentrations of adrenal steroids and the progression of immunosuppression and cachexia during HIV-infection. This raises the question of whether there is a cause-and-effect relationship between clinical progression and circulating steroid concentrations. Further investigations into the relationship between the ratio cortisol/DHEA and the immune response and cachexia should indicate the contributions of these steroids to the etiology of HIV infection and lead to the development of new therapeutic strategies.

Serum lipid concentration with reference to the clinical and immunological status of HIV infected men.

We investigated the serum concentrations of free fatty acids (FFA), cholesterol, phopholipids and triglycerides in HIV-positive men (n = 50) from three behaviour groups: heterosexuals (n = 16), drug addicts (n = 18) and homosexuals (n = 16) and a control group of HIV-negative men (n = 25). The circulating concentrations of lipids were analyzed with reference to the clinical status of infection and the absolute CD4 cell count. According to the clinical progression of HIV infection the patients were divided into two groups (CDC 1987 criteria): stages II and III (n = 28) and stage IVC (n = 22). HIV-positive men had higher polyunsaturated fatty acids (PUFA) (+100%), p < 0.001) only in the II and III stages, lower cholesterol (-25% to -40%, p < 0.001) and lower phospholipids (-25%, p < 0.001) for the two stages than in the controls. The triglycerides were increased only in stage IVC patients compared to the controls (+110%, p < 0.001). According to their CD4 cell count, the patients were divided into four groups: > 400 (n = 11), 400-150 (n = 9), 150-50 (n = 9) and < 50 (n = 19). Regardless of the CD4 count, the PUFA were significantly higher (+50% to +125%) and cholesterol (-35% to -45%) and phospholipids (-25% to -30%) lower than in the controls in all HIV-infected men except the patients with 400-150 CD4. Only the HIV-positive patients with < 50 CD4 cells had elevated triglycerides (+97%, p < 0.001). There was a significant negative correlation between the CD4 cell count and the serum triglyceride concentrations (r = -0.31, p < 0.03). In conclusion, the most elevated PUFA occurred in HIV-positive patients with > 400 CD4, while hypertriglyceridaemia is prevalent in very advanced stages of infection (with < 50 CD4). This suggests that there is a relationship between the circulating PUFA and triglycride levels and the progression of infection and immune suppression. The disturbances in lipid metabolism must now be correlated with the underlying metabolic, hormonal and cytokine changes and their role in the development of significant malnutrition and immune perturbations.