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In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.

Approximately 4 million persons in the United States and probably more than 100 million persons worldwide are infected with hepatitis C virus. The virus has the unique ability to cause persistent infection in susceptible hosts after parenteral or percutaneous transmission, and its underlying mechanisms are not well understood. The immunologic correlates of protection and viral clearance and the pathogenesis of liver injury are yet to be defined, but recent studies suggest the importance of cell-mediated immune responses. Although 70% to 80% of infected persons become chronic carriers, most have relatively mild disease with slow progression. However, chronic and progressive hepatitis C carries significant morbidity and mortality and is a major cause of cirrhosis, end-stage liver disease, and liver cancer. Development of an effective hepatitis C virus vaccine is not imminent, but recent advances in technology and basic knowledge of molecular virology and immunology have engendered novel approaches to the fundamental problems encountered in vaccine development. Current therapy for hepatitis C, although effective in some patients, is problematic and still evolving. Advances in modern biology and immunology promise new therapies for this important disease.

Background The sequelae during the first two decades after acute hepatitis C virus (HCV) infection have been well studied, but the outcome thereafter is unknown. Objective To conduct an extended study of the natural history of HCV infection by using archived serum specimens originally collected between 1948 and 1954. Design Retrospective cohort study. Setting A university, a Veterans Affairs medical center, and a medical follow-up agency that had access to the serum specimens and accompanying demographic and medical records. Participants 8568 military recruits who were evaluated for group A streptococcal infection and acute rheumatic fever between 1948 and 1954. Blood samples were taken from the recruits and, after testing, were stored frozen for almost 45 years. Measurements The presence of antibodies to HCV was determined by enzyme-linked immunoassay, supplementary recombinant immunoblot assay, and polymerase chain reaction for HCV RNA. Morbidity and mortality were also assessed. Results Of 8568 persons, 17 (0.2%) had positive results on enzyme-linked immunosorbent assay and recombinant immunoblot assay. The rate was 1.8% among the African-American persons and 0.1% among the white persons in the total sample (relative risk, 25.9 [95% CI, 8.4 to 80.0]). During the 45-year follow-up, liver disease occurred in 2 of the 17 HCV-positive persons (11.8%) and 205 of the 8551 HCV-negative persons (2.4%) (ethnicity-adjusted relative risk, 3.56 [CI, 0.94 to 13.52]). Seven of the 17 HCV-positive persons (41 %) and 2226 of the 8551 HCV-negative persons (26%) had died by December 1996 (ethnicity-adjusted relative risk, 1.48 [CI, 0.8 to 2.6]). Of persons who were HCV-positive, 1 (5.9%) died of liver disease 42 years after the original phlebotomy, 5 (29%) died of non-liver-related disease a median of 37 years after the original phlebotomy, and 1 (5.9%) died of unknown causes. One hundred nineteen HCV-negative persons (1.4%) died of liver disease. Conclusions The rate of HCV infection from 1948 to 1954 among a sample of military recruits parallels that among present-day military recruits and volunteer blood donors. During 45 years of follow-up, HCV-positive persons had low liver-related morbidity and mortality rates. This suggests that healthy HCV-positive persons may be at less risk for progressive liver disease than is currently thought.

To the Editors: Transfusion-associated non-A, non-B hepatitis has recently been shown to result usually from infection with the hepatitis C virus (HCV) (1). Although we recognize that non-A, non-B ...

Fifteen patients with chronic type B hepatitis were treated with corticosteroids in a randomized, double-blind, placebo-controlled trial lasting 28 days. Ten patients received prednisolone, 60 mg/d for 2 weeks, then 30 mg/d for another 2 weeks; 5 patients received placebo. Serum aminotransferase levels decreased significantly during prednisolone therapy but 4 to 10 weeks after abrupt withdrawal of the drug, they rebounded to levels greater than those before treatment. This exacerbation of disease lasted for several months and was prolonged and symptomatic in 3 patients. Hepatitis B virus levels did not change substantially during treatment. Follow-up examinations showed no improvement in biochemical or serologic features of the disease in any of the 15 patients; follow-up liver biopsies showed a worsening in 4 of 7 treated patients but in 0 of 5 control patients. Thus, a 28-day course of prednisolone produced no beneficial effects in patients with mild-to-moderate chronic type B hepatitis; on the contrary, such treatment may be harmful.

We have treated 6 chronic alcoholics and identified an additional 19 reported in the literature who developed severe hepatotoxicity from acetaminophen taken in apparently moderate doses. The clinical disease in these 25 patients had a characteristic pattern: mild to moderate jaundice; mild to severe coagulopathy; and strikingly abnormal aminotransferase levels, values inconsistent with either acute alcoholic hepatitis or viral hepatitis. The possible causes for the injury from ostensibly nontoxic drug levels appear to be either the induction by chronic alcohol intake of the cytochrome P-450 system responsible for converting acetaminophen to a toxic metabolite, or the effect of alcoholism and the associated malnutrition in reducing the glutathione concentration, responsible normally for preventing hepatotoxicity by conjugation with the toxic metabolite. The research data pertaining to the apparent enhanced toxicity from chronic alcoholism are reviewed. Despite the low frequency of ethanol-potentiated acetaminophen hepatotoxicity, alcoholics should be cautioned about the use of acetaminophen while they persist in heavy consumption of alcohol.

Excerpt Numerous reports describe severe hepatotoxic effects from large doses of acetaminophen ingested with suicidal intent (1). However, there are only occasional reports of hepatotoxicity from t...

The mechanism of action of hepatitis B immune globulin (HBIG) and immune serum globulin was sought in a reanalysis of a Veterans Administration cooperative study on needle-stick exposure to hepatitis B surface antigen (HBsAg)-positive blood. Sera from 296 exposed persons were tested for HBsAg, antibody to HBsAg (anti-HBs), and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay. Type B hepatitis developed in three HBIG (2%) and in 12 ISG (8%) recipients. In contrast, subclinical infection (development of HBsAg or anti-HBs and anti-HBc without symptoms or jaundice) developed in 16 HBIG (10%) but only six immune serum globulin (4%) recipients. Thus, infection occurred equally in both groups but was more likely to be subclinical in HBIG recipients, indicating that HBIG permitted development of passive-active immunity to type B hepatitis. An additional 53 immune serum globulin recipients (36%) but only one HBIG recipient developed anti-HBs alone, without hepatitis, HBsAg, or anti-HBc. This response was more compatible with immunization by HBsAg than with infection. Ultracentrifugation analysis revealed occult HBsAg in the immune serum globulin but not the HBIG, indicating that some immune serum globulin preparations contain HBsAg and can induce active immunity to type B hepatitis.

Twenty-five patients with chronic type B hepatitis documented by liver biopsy were followed for 1 to 6 years with serial measurements of aminotransferase levels, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and antibody (anti-HBe), and hepatitis B virus DNA polymerase. Initially, all were positive for HBsAg and HBeAg and had elevations in serum aminotransferases. In follow-up, only one lost HBsAg reactivity. In 13, however, elevated aminotransferase levels spontaneously fell to normal and have remained normal. These 13 also had a seroconversion from HBeAg to anti-HBe, and all became negative for serum DNA polymerase. Most had a fall in HBsAg titer. This seroconversion occurred concurrently with or several months before the fall in aminotransferase levels. In contrast, the 12 persons who remained HBeAg positive continued to have elevated aminotransferase levels. All 10 of these patients who were initially positive for DNA polymerase remained positive. These data suggest that many patients with chronic type B hepatitis eventually have a spontaneous remission in clinical and biochemical evidence of active disease, usually heralded or accompanied by the disappearance of HBeAg and DNA polymerase.

Excerpt Persons with hemophilia are at unusually high risk of developingacuteviral hepatitis as a result of their need for repeated treatment with blood products. Although less than one fourth of a...