Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC

Clinical aspects of Common Variable Immunodeficiency : There is more to the image than meets the eye

Common variable immunodeficiency (CVID) is the most common and most diverse primary antibody deficiency. The heterogeneous group consists of patients with variable (recurrent) infections andnon-infectious complications such as autoimmunity, lymphoproliferative (granulomatous) disease, chronic lung disease, enteropathy, lymphoma and other malignancies. The largest problem for CVID patients is the development of the non-infectious complications that are associated with excess morbidity and mortality due to organ dysfunction and failure. In the current thesis we set out to identify clinical and therapeutic aspects and B- and T cell parameters that might predict which patients are prone to complications in order to improve clinical follow up and treatment of CVID patients. Our research has shown that the clinical spectrum in CVID patients is divers and that the development of infectious and non-infectious complications continues despite Ig therapy. Common complications are autoimmune, gastrointestinal disease and lymphoproliferative disease. This is probably due to the combined immune dysregulation in the B and T cell compartment in CVID patients.We have showed that the prevalence of structural airway disease (bronchiectasis) increased during follow-up despite adequate IgG trough levelsand despite the reduction of respiratory infections. Interstitial lung disease was associated with the presence of autoimmunity and distinct cellular distribution of T and B cell subpopulations. Both chronic pulmonary and gastrointestinal disease have been associated with excess morbidity and early mortality in CVID patientsTherefore, early detection and monitoring of progression of such conditions is essential. Finally, we found a considerable diagnostic delay for CVID patients, especially in those patients who were dominated by non-infectious complications. Failure to diagnose CVID and therefore delaying the start of adequate therapy for specific conditions can cause considerable morbidity. It remains important to increase awareness among doctors for the variable clinical presentations and manifestations of CVID