Faculty Bibliography

The use of highly active antiretroviral therapy (HAART) has extended the healthy lifespan of patients infected with human immunodeficiency virus (HIV); deaths among people with AIDS declined for the first time in 1996, after the institution of this therapeutic approach. As the life expectancy of HIV-infected patients increases, greater attention will need to be focused on the recognition and management of potentially severe concurrent illnesses that may increase their mid- to long-range morbidity and mortality. The incidence of infection by hepatitis C virus (HCV) is increased among patients with HIV disease, reflecting shared epidemiological risks. HCV not only may have an impact on the health status of HIV-infected patients but also may decrease their quality of life and increase their health care costs. Although clinicians have been reluctant to treat viral hepatitis C in the HIV-infected population, this therapeutic nihilism is unwarranted. The majority of studies have concluded that treatment of hepatitis C in HIV-infected patients results in an initial efficacy and long-term response similar to those in the HIV-seronegative population. Furthermore, treatment of HCV infection in HCV/HIV-coinfected patients may improve tolerance for antiretroviral medications. Physicians caring for patients with HIV infection require up-to-date information to make rational decisions regarding HCV coinfection to ensure that morbidity and mortality are minimized and that quality of life and medical care costs are optimized

As the life expectancy of patients with HIV infection increases, greater attention will need to be focused on concurrent illnesses, such as viral hepatitis, that may increase mid- to long-range morbidity and mortality. The incidence of viral hepatitis is increased in patients with HIV disease, reflecting the epidemiologic risks that these two conditions share. Coinfection with HIV seems to adversely affect the natural history of hepatitis C but may actually reduce the hepatic damage associated with hepatitis B. Immunosuppression due to HIV does not seem to significantly affect hepatitis A, E, or G. Clinicians have been reluctant to treat viral hepatitis in the HIV-infected population, but this therapeutic nihilism is unwarranted. Most studies have concluded that the treatment of hepatitis C in HIV-infected patients results in an initial efficacy and a long-term response similar to those seen in the HIV-seronegative population. Although the efficacy of interferon is reduced against hepatitis B, some nucleoside analogues are effective.

Patients infected with HIV are susceptible to a variety of hepatic processes that are related to immunosuppression or are associated with the risk factors of homosexuality and parenteral drug use. These processes present in a myriad of ways including fever, right upper quadrant pain, and hepatomegaly, or simply as asymptomatic elevations of liver tests. Care of these patients demands systematic evaluation and treatment to ensure that morbidity and mortality are minimized and quality of life and medical care costs are optimized

We describe the isolation of naturally occurring human intestinal defensins HD-5 and HD-6 from ileal neobladder urine and ileal mucosa. Using an antibody-based detection assay, we found multiple N-terminally processed forms of HD-5. The predominant HD-5 forms in tissue were longer than those in neobladder urine (amino acid (aa) 23-94 and 29-94 versus aa 36-94, 56-94 and 63-94) suggesting that Paneth cells store prodefensin that is processed to mature defensin during or after degranulation. Search for mature HD-6 yielded aa 69-100 as the predominant form in both sources. The ileal neobladder is a promising model to study human Paneth cell secretion

Adenovirus infection of the gastrointestinal tract in human immunodeficiency virus (HIV)-infected patients is rarely reported, probably because of a lack of familiarity of most pathologists with diagnostic criteria during routine light microscopy and possible misidentification as cytomegalovirus infection. We studied colonoscopic biopsy specimens from 135 HIV-infected patients with clinically suspected cytomegalovirus colitis during a 4.5-year period to morphologically identify the presence of adenovirus infection. Immunohistochemical staining for adenovirus was performed for confirmation on all suspected cases. Adenovirus infected cells showed characteristic amphophilic or eosinophilic nuclear inclusions, predominantly affecting the surface epithelium and characteristically involving goblet cells. Sixteen cases showed morphologic features of adenovirus infection, all confirmed by immunohistochemistry. Twelve cases also showed cytomegalovirus infection, whereas 4 showed adenovirus alone. In 10 cases, adenovirus colitis was not recognized during initial routine histopathologic diagnostic evaluation. Adenovirus inclusions also were discovered in the stomach, the duodenum, and the liver in single cases. Conclusions are as follows: (1) Adenovirus colitis has been underdiagnosed at our institution and, we suspect, in general. (2) The morphologic features and nuclear inclusions of adenovirus colitis are characteristic and can be identified reliably by routine light microscopy. (3) Adenovirus infection also may be diagnosed morphologically in extracolonic sites, such as the stomach, the small intestine, and the liver. (4) Coinfection of adenovirus with cytomegalovirus and other agents is seen frequently, but, less frequently, adenovirus may be identified as a sole pathogen

Ten patients with AIDS and cytomegalovirus (CMV) gastrointestinal infection were included in an open-label study to evaluate the safety, efficacy, and pharmacokinetics of 90 mg of intravenous foscarnet/kg of body weight twice daily accompanied by (pre)hydration of 500 to 750 ml. Efficacy was documented endoscopically, while safety was evaluated clinically by patient reports and physical and laboratory observation. The pharmacokinetics of foscarnet was evaluated after the first dose and following approximately 20 days of therapy. Nine patients (90%) responded histopathologically, nine (90%) responded endoscopically, and nine (90%) responded symptomatically to foscarnet therapy. Adverse events resulted in discontinuance of medication in the case of one patient. The mean maximal concentration was 621 microM following the first dose and 687 microM at steady state (P = 0.11). The apparent elimination rate constant and elimination half-life were not different between dose 1 and steady state. There were no significant changes in foscarnet excretion or renal clearance between dose 1 and steady state. The steady-state volume of distribution was 23.4 liters following the first dose and 19.0 liters at steady state (P < 0.002). Twice-daily foscarnet appeared to be safe and efficacious in the treatment of CMV gastrointestinal disease in this study, resulting in endoscopic or histologic improvement in 9 of the 10 (90%) patients. Minor changes in clearance and volume of distribution noted at steady state compared to single-dose administration are readily explained by study design, known information about foscarnet pharmacokinetics, and changes in body weight and creatinine clearance in the patients

Liver involvement with opportunistic infections and neoplasms is a well-recognized component of AIDS, affecting most patients. The cause of hepatic disease in these patients may be divided into hepatitis, granulomatous disease, mass lesions, vascular lesions, hepatotoxic drugs, and nonspecific findings. With a rational approach, most patients with AIDS and liver disease can be diagnosed and treated in a cost-effective manner with low morbidity

Diarrhea is a major complication of HIV infection and adversely impacts health care costs, quality of life, and even survival of patients. There is a wide variety of potential causes of diarrhea in HIV-infected patients, and the number of pathogens found continues to increase with time. In addition, there is some controversy concerning the role of some organisms in the pathogenesis of diarrhea and the appropriate diagnostic evaluation of affected patients. This article reviews our current understanding of these pathogens and some of the diagnostic and therapeutic approaches for diarrhea associated with HIV infection

Wasting decreases immune function, and is associated with decreased quality of life and increased mortality in patients with AIDS. Many modalities have been used in the treatment of this problem, but few promote positive nitrogen balance and increase body cell mass. We studied 21 patients with AIDS-related weight loss, defined as loss of greater than 5% usual body weight, or a baseline of less than 100% ideal body weight (IBW). Patients were treated with oxandrolone, 10 mg orally, twice daily. All subjects were men who acquired HIV through unprotected homosexual sex, with the exception of one woman who acquired the disease through unprotected heterosexual contact. The mean age of patients was 38 years, and mean CD4 count was 55. All patients were evaluated with bioelectrical impedance analysis (BIA). BIA mean values for weight, body cell mass (BCM), fat, intracellular water (ICW) and extracellular water (ECW) were calculated for patients at baseline, and then for those patients who took the medication for 30 days, 60 days, 90 days, and 120 days, respectively. Mean changes from baseline in weight, BCM, fat and ICW were significant (p is less than 0.05) at all points in time (except at 120 days, due to the small sample size at this time). At 30 days, weight increased by a mean of 6.5 pounds, BCM increased by a mean of 3.4 pounds, fat increased by a mean of 1.6 pounds, and ICW increased by a mean of 1.4 liters. At 60 days, weight increased by a mean of 12.9 pounds, BCM increased by a mean of 6.9 pounds, fat increased by a mean of 3.0 pounds, and ICW increased by a mean of 2.9 liters. At 90 days, weight increased by a mean of 11.3 pounds, BCM increased by a mean of 4.2 pounds, fat increased by a mean of 5.2 pounds, and ICW increased by a mean of 1.8 liters. At 120 days, weight increased by a mean of 16.0 pounds, BCM increased by a mean of 6.6 pounds, fat increased by a mean of 6.8 pounds, and ICW increased by a mean of 2.7 liters. Change in ECW was significant (p is less than 0.05) only at 90 days. At that time, ECW was decreased by a mean of 1.1 liters from baseline. Of note, values for mean body composition, including % ideal body weight, % BCM, and % fat were also recorded at baseline, and at 30-day intervals thereafter, and were noted to rise steadily throughout the study period. Percent IBW increased from 92.2% at baseline to 101.3% at 90 days and to 106.7% at 120 days. Treatment with oxandrolone resulted in a significant (p is less than 0.05) increase in weight gain, and importantly, in BCM at 90 days. A significant (p is less than 0.05) increase in ICW and a significant (p is less than 0.05) decrease in ECW were also found to occur at 90 days. Final analysis for the 120-day follow-up has not been completed at this time. Thus, the common nutritional abnormalities that occur in AIDS-related weight loss and wasting were reversed