Faculty Bibliography

Because of shared modes of transmission, co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common. Co-infection with HIV increases HCV virus load, liver-related mortality, and the risk of sexual and perinatal transmission of HCV, and it may accelerate HCV disease progression. With combination interferon (IFN)-alpha 2b/ribavirin or pegylated IFN-alpha 2b/ribavirin therapy, long-term remission is possible for HCV-infected patients. Preliminary evidence suggests that the combination of IFN-alpha 2b/ribavirin can achieve similar response rates in HCV/HIV-co-infected individuals with no adverse effect on HIV RNA concentrations. Although adverse effects are more frequent with combination therapy than with IFN-alpha monotherapy, most are manageable. In addition, few instances of drug-drug antagonism have been reported among drugs used to treat each disease, although further study is necessary. Ribavirin-associated hemolytic anemia is a potential problem in a patient population that is already susceptible to anemia but is manageable with recombinant human erythropoietin (epoetin alfa)

Nonnucleoside reverse transcriptase inhibitors (NNRTIs), particularly nevirapine, have been associated with hepatotoxicity. We performed a retrospective study to determine the incidence of NNRTI hepatotoxicity in a group of HIV-infected patients from a New York City practice. These patients are predominantly homosexual white males. We also analyzed the effect of coinfection with hepatitis B (HBV) or hepatitis C (HCV) virus. In total, 272 patients received NNRTIS: 40 (15%) received delavirdine, 91 (33%) received efavirenz, and 141 (52%) received nevirapine. Of the patients with known hepatitis status, 18 of 190 (9%) were coinfected with HBV, and 24 of 205 were coinfected (12%) with HCV. The overall rate of grade 3 to 4 elevations in aspartate aminotransferase (AST) or alanine aminotransferase (ALT) was 3 of 272 (1.1%) and did not differ significantly among the three NNRTIs. HBV or HCV was not associated with a significant increase in AST or ALT elevations. We conclude that NNRTIs are relatively free from hepatotoxicity in this population, despite the presence of coinfection with HBV or HCV

OBJECTIVE:To compare the primary diagnoses assigned by general surgical pathologists on a series of 103 consecutive colon biopsies from individuals infected with human immunodeficiency virus (HIV) with diagnoses rendered by a pathologist with extensive experience in gastrointestinal pathology in HIV/acquired immunodeficiency syndrome. DESIGN/METHODS:New sections were cut from paraffin blocks of 103 consecutive colon biopsies taken during colonoscopies of 82 different HIV-infected patients; all new sections were stained with hematoxylin-eosin. These individuals either had negative stool studies or had failed to respond to therapy and had chronic large bowel symptoms, such as frequent small volume-type diarrhea, tenesmus, and/or bright red blood per rectum. Immunohistochemistry for cytomegalovirus (CMV) was performed on 18 of 22 specimens originally diagnosed with CMV colitis. RESULTS:The initial study yielded 70 (68%) negative or nonspecific diagnoses, 22 (21%) cases of CMV colitis, 5 (5%) Cryptosporidium diagnoses, 2 cases each of adenomatous polyps and Kaposi sarcoma, and 1 case each of spirochetosis and squamous cell carcinoma of the anorectum. Review of the recuts yielded 64 (62%) negative or nonspecific diagnoses, 12 (12%) new adenovirus infections (3 combined with CMV), and 11 (11%) lone CMV infections. Three attaching and effacing bacterial infections were diagnosed, 1 with adenovirus coinfection. A total of 4 spirochetosis cases were found on review. Seven (7%) of the biopsies showed at least 1 coinfection. Nine biopsies had features suggestive of inflammatory bowel disease. CONCLUSIONS:Colonoscopy with biopsy after negative stool studies or failure to respond to therapy yielded a high proportion of negative or nonspecific diagnoses. Adenovirus and enteropathogenic bacterial infections had been totally overlooked on initial examination. It takes particular experience to evaluate gastrointestinal biopsies from HIV-infected patients.

OBJECTIVE: To determine the change in the percentage of proliferative and activated lymphocytes in gut-associated lymphoid tissue (GALT) in HIV-1-infected subjects compared with that in uninfected controls. METHODS: We measured the percentage of proliferative (Ki-67+) and activated (CD-69+, HLA-DR+, CD45RO+) lymphocytes from GALT and peripheral blood in chronically HIV-1-infected (12) and uninfected (9) individuals. RESULTS: The percentage of proliferative GALT CD4+ T cells was increased in HIV-1-infected control subjects compared with that in uninfected controls (p <.007). Based on immunohistochemical staining, proliferative T cells were principally located in the parafollicular area surrounding lymphoid aggregates. The percentage of activated GALT lymphocytes, however, was not significantly different in HIV-1-infected individuals, whereas it was significantly increased in the peripheral blood of HIV-1-infected individuals. The percentage of peripheral blood lymphocytes trafficking to the intestine was also not significantly different in HIV-1-infected individuals compared with that in uninfected controls. CONCLUSIONS: CD4+ T cell proliferation in GALT is increased in HIV-1 infection without a significant alteration in the percentage of peripheral blood T cells trafficking to the gastrointestinal mucosa