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Context: Use of antiretroviral drugs, including protease inhibitors, for treatment of human immunodeficiency virus (HIV) infection has been anecdotally associated with hepatotoxicity, particularly in persons coinfected with hepatitis C or B virus.Objectives: To ascertain if incidence of severe hepatotoxicity during antiretroviral therapy is similar for all antiretroviral drug combinations, and to define the role of chronic viral hepatitis in its development.Design: Prospective cohort study.Setting: University-based urban HIV clinic.Patients: A total of 298 patients who were prescribed new antiretroviral therapies between January 1996 and January 1998, 211 (71%) of whom received protease inhibitors as part of combination therapy (median follow-up, 182 days) and 87 (29%) of whom received dual nucleoside analog regimens (median follow-up, 167 days). Chronic hepatitis C and B virus infection was present in 154 (52%) and 8 (2.7%) patients, respectively.Main Outcome Measure: Severe hepatotoxicity, defined as a grade 3 or 4 change in levels of serum alanine aminotransferase and aspartate aminotransferase, evaluated before and during therapy.Results: Severe hepatotoxicity was observed in 31 (10.4%) of 298 patients (95% confidence interval [CI], 7.2%-14.4%). Ritonavir use was associated with a higher incidence of toxicity (30%; 95% CI, 17.9% -44.6%). However, no significant difference was detected in hepatotoxicity incidence in other treatment groups, ie, nucleoside analogs (5.7%; 95% CI, 1.2%-12.9%), nelfinavir (5.9%; 95% CI, 1.2%-16.2%), saquinavir (5.9%; 95% CI, 0.15%-28.7%), and indinavir(6.8%; 95% CI, 3.0%-13.1 %). Although chronicviral hepatitis was associated with an increased risk of severe hepatotoxicity among patients prescribed nonritonavir regimens (relative risk, 3.7; 95% CI, 1.0-11.8), most patients with chronic hepatitis C or B virus infection (88%) did not experience significant toxic effects. Rate of severe toxicity with use of any protease inhibitor in patients with hepatitis C infection was 12.2% (13/107; 95% CI, 6.6%-19.9%). In multivariate logistic regression, only ritonavir (adjusted odds ratio [AOR], 8.6; 95% CI, 3.0-24.6) and a CD4 cell count increase of more than 0.05 x 10(9)/L (AOR, 3.6; 95% CI, 1.0-12.9) were associated with severe hepatotoxicity. No irreversible outcomes were seen in patients with severe hepatotoxicity.Conclusions: Our data indicate that use of ritonavir may increase risk of severe hepatotoxicity. Although hepatotoxicity may be more common in persons with chronic viral hepatitis, these data do not support withholding protease inhibitor therapy from persons coinfected with hepatitis B or C virus. [ABSTRACT FROM AUTHOR]

We wished to determine the incidence of human immunodeficiency virus-related high-grade non-Hodgkin's lymphoma (NHL) and identify factors associated with the development of NHL in patients receiving zidovudine. Data are from a 2-year prospective, observational, multisite study of 1030 patients with the acquired immunodeficiency syndrome (AIDS) and advanced AIDS-related complex who received zidovudine. Non-Hodgkin's lymphoma developed in 24 (2.3%) of 1030 patients who received zidovudine during 1463 person-years of follow-up (rate, 1.6 per 100 person-years of therapy). The relative hazard for development of NHL was stable throughout 2 years of therapy, with the risk of developing NHL 0.8% for each additional 6 months of therapy. Factors associated with development of NHL were a prior diagnosis of Kaposi's sarcoma, herpes simplex virus infection, or lower mean neutrophil count. Less strongly associated was a prior diagnosis of oral hairy leukoplakia or homosexual transmission of HIV. By Cox proportional hazards analysis, a prior diagnosis of Kaposi's sarcoma, cytomegalovirus disease, or oral hairy leukoplakia was most strongly associated with development of NHL. Our study demonstrates a relatively high incidence of NHL in patients with advanced human immunodeficiency virus disease who are undergoing antiretroviral therapy and suggests possible risk factors for development of NHL. [ABSTRACT FROM AUTHOR]

As part of an institution-wide program to enhance the education of physicians in diagnosing and treating alcohol dependence and abuse, a comprehensive survey was conducted in which all new admissions to the adult inpatient services of The Johns Hopkins Hospital were screened for alcoholism. The prevalence of screen-positive alcoholism, by department, was as follows: medicine (25%), psychiatry (30%), neurology (19%), obstetrics-gynecology (12.5%), and surgery (23%). Detection rates by the house staff and faculty physicians caring for those patients who screened positively were less than 25% in surgery and obstetrics-gynecology, between 25% and 50% in neurology and medicine, and greater than 50% in psychiatry. However, physicians were less likely to identify as alcoholic those patients with higher incomes, higher education, or private medical insurance; women; and those who denied heavy alcohol intake. Physician-instituted treatment rates for those patients diagnosed by the physician as having nonrecovered alcoholism were less than 50% in surgery and obstetrics-gynecology, between 50% and 75% in medicine and neurology, and 100% in psychiatry. The extent to which the physicians intervened while the patient was hospitalized correlated with the patient's reported change in alcohol use after discharge. Recommendations based on these data are being incorporated into the medical education curriculum. [ABSTRACT FROM AUTHOR]

Unlabelled: OBJECTIVES--To determine if racial-ethnic differences exist in survival, disease progression, and development of myelosuppression in zidovudine-treated patients with advanced human immunodeficiency virus (HIV) disease. DESIGN--Prospective observational study.Setting: -Hospital and private clinics in 12 metropolitan centers.Patients: -The study included 754 non-Hispanic white, 165 black, and 106 Hispanic patients with the acquired immunodeficiency syndrome (AIDS) or advanced AIDS-related complex (ARC) who received up to 2 years of zidovudine therapy. OUTCOME MEASURES--Survival, development of Pneumocystis carinii pneumonia (PCP), other opportunistic infections, and myelosuppression. RESULTS--At initiation of zidovudine therapy, Hispanic and particularly black patients had more advanced HIV disease than white patients, as indicated by lower baseline CD4+ counts, hematocrits, and AIDS-defining diagnoses. Black patients with AIDS also had a worse prognosis compared with white and Hispanic patients with AIDS. The product-limit survival rates at 2 years for white, black, and Hispanic patients with AIDS were 40%, 27%, and 39%, respectively (black vs white, P = .01; Hispanic vs white, P = .32, by the log-rank test). The respective proportions of patients who developed PCP at 2 years were 46%, 66%, and 44% (black vs white, P = .0001; Hispanic vs white, P = .86) and for other opportunistic infections the proportions were 56%, 63%, and 63%, respectively (black vs white, P = .03; Hispanic vs white, P = .09). There were no significant racial-ethnic differences in survival or in the development of opportunistic infections for patients with ARC, and there were no differences in the incidence of myelosuppression or dose reduction or suspension for patients with either ARC or AIDS. After adjusting for more advanced HIV disease (mainly low CD4+ counts and hematocrits), black race was no longer a significant independent predictor of survival. Adjustment for racial differences in the use of PCP prophylaxis accounted for most of the excess risk for the development of PCP in black patients compared with white patients with AIDS. CONCLUSIONS--Racial differences in survival and the development of opportunistic infections are mainly due to the more advanced HIV disease in black patients when zidovudine therapy is started and to their less frequent use of PCP prophylaxis. Innovative approaches are needed to ensure more widespread use of and earlier access to zidovudine therapy and PCP prophylaxis. [ABSTRACT FROM AUTHOR]

Although alcoholism is prevalent in both general and inpatient populations, barriers to its timely diagnosis and effective treatment exist. These are often attributed to physicians' inadequate understanding and skill development and negative attitudes toward the disease. All Johns Hopkins' medical students and house staff, during 1986 through 1987, received a self-administered survey of their attitudes, skills, perceived role responsibility, knowledge, and reported practices with regard to alcoholism. Results indicate a strong relationship between perceived role responsibility, confidence in skills, and reported screening and referral practices among students and house staff. Knowledge levels strengthened the association between skills and practices for medical students. House staff perceived less of a responsibility for screening than medical students. There was a trend toward lower confidence and more negative attitudes among house staff than medical students. The results point to areas where educational interventions can be improved to enhance quality of care and outcomes for this major chronic disease. [ABSTRACT FROM AUTHOR]

Context: The US Public Health Service and the International AIDS Society-USA recently published recommendations for antiretroviral therapy (ART) for persons infected with human immunodeficiency virus (HIV); however, anecdotal evidence suggests that HIV-infected injection drug users (IDUs) may not be receiving optimal care as defined by the recommendations., Objective: To assess ART use in HIV-infected IDUs., Design: A cross-sectional survey of self-reported ART use between July 1996 and June 1997 in IDUs., Setting: A community-based clinic affiliated with Johns Hopkins University, Baltimore, Md., Participants: A total of 404 HIV-infected IDUs with CD4+ cell counts less than 0.50 x 10(9)/L recruited into a longitudinal study in 1988 and 1989., Main Outcome Measure: Self-reported ART use was assessed: no current therapy, monotherapy, or combination therapy with or without a protease inhibitor., Results: One half (199/404 [49%]) of patients reported no recent ART. A total of 14% (58/404) had monotherapy, 23% (90/404) were receiving combination therapy without a protease inhibitor, and 14% (57/404) had triple-combination therapy with a protease inhibitor. A multivariate analysis of factors associated with ART showed that care continuity and recent HIV-related outpatient visit (odds ratio [OR], 4.30; 95% confidence interval [CI], 2.36-7.81 and OR, 2.84; 95% CI, 1.66-4.88, respectively), CD4+ cell count of less than 0.20 x 10(9) (OR, 2.41; 95% CI, 1.51-3.84), no current drug use and being in drug treatment (OR, 2.16; 95% CI, 1.34-3.47; OR, 2.12; 95% CI, 1.23-3.66, respectively), and unemployment (OR, 2.31; 95% CI, 1.21-4.40) were associated with reporting ART use. In other analysis, less likely to receive protease inhibitors were current drug injectors (OR, 0.5; 95% CI, 0.3-1.0) and those recently incarcerated (OR, 0.2; 95% CI, 0.03-0.9), but patients with acquired immunodeficiency syndrome were more likely to receive protease inhibitors (OR, 2.0; 95% CI, 0.9-4.6). Protease inhibitor use doubled (P<.01) from July and December 1996 to January and June 1997 (7.7% and 14.8%, respectively)., Conclusions: Those IDUs infected with HIV who were not receiving ART tended to be active drug users without clinical disease who have less contact with health care providers. Although we do not have information on clinical judgment regarding treatment decisions or whether persons were prescribed therapy not taken, the proportion of subjects reporting receiving ART suggests that strategies for improving treatment in this population are indicated. Expanding simultaneous treatment services for HIV infection and substance abuse would enhance the response to these related epidemics.