Persistent immune activation in HIV-1 infection is associated with progression to AIDS

Background: HIV-1 infection is characterized by chronic generalized CD8 and CD4 T cell hyperactivation, the biological effect of which is not understood. Objective: To study the relation between chronic immune activation and CD4 T cell depletion in HIV-1 infection. Design: Prospective cohort study among participants of the Amsterdam Cohort Studies on HIV-1 infection and AIDS who have a known seroconversion date (n = 102). Methods: CD4 and CD8 T cell activation marker expression was analysed by FACScan before and after seroconversion (1 and 5 years after seroconversion); T cell proliferation and T cell numbers were also measured. Cox proportional hazard analyses were used to study the predictive value of these parameters for progression to AIDS. Results: Preseroconversion low CD4 T cell numbers or elevated levels of CD4 T cell activation were associated with increased risk for development of AIDS after HIV-1 seroconversion. Progression to AIDS was associated with loss of both CD4 and CD8 naive T cells. The predictive value of CD8 T cell activation was confirmed and, in addition, in the course of infection low CD4 T cell counts and increasing proportions of dividing CD4 T cells, dividing CD8 T cells or elevated CD4 T cell activation marker expression became independent predictors of progression to AIDS. Conclusions: Increased T cell activation has predictive value for HIV-1 disease progression even before seroconversion. These data support the hypothesis that persistent hyperactivation of the immune system may lead to erosion of the naive T cell pool and CD4 T cell depletion. (C) 2003 Lippincott Williams Wilkin

Does rapid genetic counseling and testing in newly diagnosed breast cancer patients cause additional psychosocial distress? Results from a randomized clinical trial

Purpose:Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of primary surgical treatment. In this article, we report on the psychosocial impact of RGCT.Methods:Newly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits.Results:Between 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes.Conclusions:In this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects