Although generalized T-cell activation is an important factor in chronic HIV disease pathogenesis, its role in primary infection remains poorly defined. To investigate the effect of immune activation on T-cell changes in subjects with early HIV infection, and to test the hypothesis that an immunologic activation "set point" is established early in the natural history of HIV disease, a prospective cohort of acutely infected adults was performed. The median density of CD38 molecules on CD4 ؉ and CD8 ؉ T cells was measured longitudinally in 68 antiretroviral-untreated individuals and 83 antiretroviraltreated individuals. At study entry, T-cell activation was positively associated with viremia, with CD8 ؉ T-cell activation levels increasing exponentially at plasma HIV RNA levels more than 10 000 copies/mL. Among untreated patients, the level of CD8 ؉ T-cell activation varied widely among individuals but often remained stable within a given individual. CD8 ؉ T-cell activation and plasma HIV RNA levels over time were independently associated with the rate of CD4 ؉ T-cell loss in untreated individuals. These data indicate that immunologic activation set point is established early in HIV infection, and that this set point determines the rate at which CD4 ؉ T cells are lost over time. IntroductionUntreated HIV-1 infection is associated with a gradual loss of peripheral CD4 ϩ T cells. Although the direct cytopathic effect of HIV-1 on CD4 ϩ T cells almost certainly contributes to this gradual depletion, 1 most cells destined to die in vivo as a consequence of HIV infection are not productively infected with HIV. 2 This observation has led to the hypothesis that progressive CD4 ϩ T-cell depletion occurs due to indirect effects of viral replication. [3][4][5][6] The mechanism for these indirect effects of HIV replication on CD4 ϩ T-cell depletion is not understood.One widely accepted model postulates that HIV causes accelerated proliferation, expansion, and death of T cells, and that this heightened T-cell turnover eventually results in depletion or exhaustion of the regenerative capacity of the immune system. 4,5 Multiple studies have shown that HIV infection results in a state of high T-cell turnover (ie, the rates of T-cell proliferation and death are increased). For example, in vivo labeling of T cells indicates that HIV infection results in increased numbers of rapidly cycling CD4 ϩ and CD8 ϩ T cells. 7,8 These cells are primarily of memoryeffector phenotype, and are destined to proliferate and die rapidly. 9 The rate at which HIV recruits cells into this rapid turnover state is directly proportional to the level of viremia, 8 which in turn is directly related to the rate at which CD4 ϩ T cells are lost. 10 In the absence of antiretroviral treatment, markers of T-cell activation and T-cell turnover predict the rate of disease progression 11-14 and the rate of CD4 ϩ T-cell loss. 15 When antiretroviral therapy is initiated, the rate of T-cell turnover and the degree of generalized T-cell activation both decrease, suggest...

There is relatively little information in the literature on the histopathology of chronic hepatitis C in children. The Peds-C Trial, designed to test the efficacy and safety of peginterferon alfa-2a and ribavirin in children, provided an opportunity to examine liver biopsies from 121 treatment-naïve children, ages 2 to 16 (mean, 9.8 years) infected with the hepatitis C virus (HCV) and with no other identifiable cause for liver disease, signs of hepatic decompensation, or another significant nonhepatic disease. Liver biopsies were scored for inflammation, fibrosis, steatosis, and other histological features. Inflammation in the biopsy was minimal in 42%, mild in 17%, moderate in 38%, and severe in only 3%. Five had bridging fibrosis, and 2 had cirrhosis. Steatosis was absent in 56%, minimal in 34%, and mild in 10%. Inflammation scores correlated with fibrosis scores, serum alanine aminotransferase levels, and duration of infection, but not with age, body mass index z score, or HCV genotype. Fibrosis scores correlated with inflammation but not with age, HCV genotype, body mass index z score, or steatosis parameters. Steatosis correlated with serum alanine aminotransferase levels and body mass index z scores; overweight children had more fibrosis than the non-overweight. In conclusion, in this cohort of HCV-infected children, inflammation, fibrosis, and steatosis were milder than reported for treatment-naïve adults with chronic hepatitis C, but there were several with bridging fibrosis or cirrhosis. The positive correlation of inflammation with duration of infection and fibrosis and of obesity with fibrosis suggest that children with chronic hepatitis C will be at risk for progressive liver disease as they age and possibly acquire other comorbid risk factors. (HEPATOLOGY 2008;47:836-843.)

We found that PCI performed at hospitals without on-site cardiac surgery was noninferior to PCI performed at hospitals with on-site cardiac surgery with respect to mortality at 6 weeks and major adverse cardiac events at 9 months. (Funded by the Cardiovascular Patient Outcomes Research Team [C-PORT] participating sites; ClinicalTrials.gov number, NCT00549796.).