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Abstracts


Metabolic Abnormalities in HIV Infection

Adrian S. Dobs, M.D., M.H.S.,
The Johns Hopkins University School of Medicine


Hypogonadism in HIV Disease:

Pathologic evaluation of specimens from HIV-infected patients shows evidence of infiltration in both the testes and the hypothalamic-pituitary area. Testicular infection is slightly more common with cylomegalovirus, Mycobacterium avium-intracellulare, Toxoplasma gondii, or tuberculosis. In addition, HIV DNA has been found in 5 percent to 20 percent of spermatogonia and spermatocytes in the testes. Clinically, complaints possibly related to hypogonadism are nonspecific and include decreased libido, erectile dysfunction, gynecomastia, and muscle wasting. In addition, medications such as ketoconazole, heroin, alcohol, and methadone may also have direct effects on the gonads. Low serum T was originally reported at 38 percent of HIV-infected males. The prevalence of this abnormality increased with increasing level of illness so that 50 percent of active acquired immunodeficiency syndrome (AIDS) patients had levels below the normal range. These data have been corroborated by others, including Croxson et al., who reported that the defect was mainly testicular, and Lefrere et al., who found no correlation between serum T levels and gonadotropins (Lefrere, 1988). In addition to a direct HIV effect, disturbances of the hypothalamic-pituitary-gonadal axis may be a consequence of overall illness. The mechanism may be secondary to the release of cytokines by the activated phagocytic cells of the immune system.

Wasting in HIV:

Weight loss, and, more specifically, wasting, is a major problem in the care of patients with AIDS, contributing to the morbidity and mortality of the disease. The weight loss associated with HIV infection may consist of two components: acute weight loss, resulting primarily from acute secondary opportunistic infections, and chronic weight loss. Wasting has prognostic importance because death generally occurs when patients reach 66 percent of ideal body weight, similar to the degree of weight loss at which death occurs due to simple starvation. Although fat stores are preferentially depleted during starvation, loss of body cell mass (muscle and viscera) with relatively less fat loss is more common in HIV infection. Although total caloric intake at baseline did not predict subsequent wasting in the multicenter AIDS Cohort Study, recent data from metabolic studies suggest that anorexia and reduced caloric intake during episodes of opportunistic infection contribute to wasting. However, results from supplemental feeding studies in HIV-infected patients with wasting have been disappointing. Hormonal disturbances have been well-documented in HIV-infected men and may contribute to wasting. The consequences of low serum T may result in loss of lean body mass, decreased bone density, psychological changes, and sexual dysfunction. Following a large cohort of gay men, we found that declines in serum free testosterone occurred with small degrees of weight loss, before true wasting (>10 percent baseline weight) was achieved.

Treatment of HIV-Infected Men With Testosterone

The effect of testosterone treatment in this population is unknown. The decision to treat must be individualized and dependent on serum level, patient motivation, and clinical status. Rabkin et al. administered supra-physiological doses of testosterone to HIV-infected men and found improved quality of life (Rabkin, 1995). The efficacy and safety of testosterone therapy in HIV infection has been equivocal. Several studies, but not all, have shown increases in weight, lean body mass, and muscle strength with replacement. The use of other androgenic-anabolic steroids, such as nandrolone and oxandrolone, seem promising. Their long-term effects are not clear.

Other Metabolic Effects Seen in HIV Infection

With the broader use of antiretrovirals, several metabolic disturbances have been observed. The most noteworthy is a lipodystrophy or redistribution of body fat away from the peripheral ann addition to the cosmetic issues, the full health effects of this are not known, but there seems to be associated hypertriglyceridemia and glucose intolerance. Cooper et al. have postulated that the protease inhibitors act by interfering with an enzyme vital to lipid metabolism. The hyperinsulinism may be present at baseline before the use of protease inhibitors (Hadigan, 1999).

References

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  4. Coodley GO, Loveless MO, Nelson HD, Coodley MK. Endocrine dysfunction in the HIV wasting syndrome. J Acquir Immune Defic Syndr 7:46-51, 1994. Croxson TS, William EC, Miller LK, Levit CD, Senie R, Zumoff B. Changes in the hypothalamic-pituitary-gonadal axis in human immunodeficiency virus-infected homosexual men. J Clin Endocrinol Metab 68:317-21, 1989.

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  9. Hadigan C, Miller K, Corcoran C, Anderson E, Basgoz N, Grinspoon S.

    Fasting hyperinsulinemia and changes in regional body composition in HIV-infected woman. J Clin Endocrinol Metab 84:1932-7, 1999.

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  12. Rabkin JG, Rabkin R. Testosterone replacement therapy for HIV-infected men. The AIDS Reader 136-44, July/August 1995.



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