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

Screening for anal dysplasia in women with a history of human papillomavirus related lower genital tract pathology

Background: Women with a human papillomavirus related history of cervical, vaginal or vulvar high-grade dysplasia or cancer are at increased risk to develop anal dysplasia or anal cancer. Screening for anal cancer precursors (squamous intraepithelial lesions (SIL)) with high resolution anoscopy (HRA) in high-risk populations is subject of debate. In this study we evaluated standardized intra-anal SIL screening using HRA in high-risk female patients. Methods: A retrospective observational study was performed to evaluate the prevalence of intra-anal SIL in women with a history of vulvar high-grade SIL (HSIL) and perianal HSIL diagnosed at the Netherlands Cancer Institute, who were referred for intra-anal SIL screening using HRA in the MC Slotervaart between 2015 and 2017. Results: 22 female patients were screened for anal SIL using HRA. 19 females had a history of biopsy proven vulvar HSIL and 19 females had a history of biopsy proven perianal HSIL. Eleven (50%) patients had a history of multizonal HSIL at three or more perianogenital locations. No anal cancer was found at screening, 7 (32%) patients were diagnosed with anal HSIL and 7 (32%) patients with low-grade anal SIL. Conclusions: We found a high prevalence of anal HSIL in women with HPV related lower genital tract dysplasia. Intra-anal SIL screening using HRA in this high risk population seems to be justified. However, HRA is an invasive screening method. Studying other, less invasive screening methods remains important

Low Bone Mineral Density, Regardless of HIV Status, in Men Who Have Sex With Men

A high prevalence of low bone mineral density (BMD) has been reported among men with primary or chronic human immunodeficiency virus (HIV) infection. To gain further insight into the contribution of HIV infection, we compared the BMD of 41 men who have sex with men (MSM) with primary HIV infection, 106 MSM with chronic HIV infection, and a control group of 30 MSM without HIV infection. Low BMD, defined as a z score of ≥2.0 SDs below the mean at the lumbar spine or hip, was highly prevalent in all 3 groups. In the multivariate analyses, HIV infection was not associated with BMD, suggesting that low BMD previously reported in HIV-infected MSM may predate HIV acquisition. © 2012 The Author

Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population

Background: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. Aims: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. Patients: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. Methods: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. Results: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. Conclusions: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic valu

Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population

Background: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. Aims: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. Patients: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. Methods: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1-300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. Results: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. Conclusions: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic valu

Predictive Performance of Cardiovascular Disease Risk Prediction Algorithms in People Living With HIV

Immunogenetics and cellular immunology of bacterial infectious disease

Progression of liver fibrosis following acute hepatitis C virus infection in HIV-positive MSM

Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Opportunistic infections and AIDS malignancies early after initiating combination antiretroviral therapy in high-income countries

Background: There is little information on the incidence of AIDS-defining events which have been reported in the literature to be associated with immune reconstitution inflammatory syndrome (IRIS) after combined antiretroviral therapy (cART) initiation. These events include tuberculosis, mycobacterium avium complex (MAC), cytomegalovirus (CMV) retinitis, progressive multifocal leukoencephalopathy (PML), herpes simplex virus (HSV), Kaposi sarcoma, non-Hodgkin lymphoma (NHL), cryptococcosis and candidiasis. Methods: We identified individuals in the HIV-CAUSAL Collaboration, which includes data from six European countries and the US, who were HIV-positive between 1996 and 2013, antiretroviral therapy naive, aged at least 18 years, hadCD4+ cell count and HIV-RNA measurements and had been AIDS-free for at least 1 month between those measurements and the start of follow-up. For each AIDS-defining event, we estimated the hazard ratio for no cART versus less than 3 and at least 3 months since cART initiation, adjusting for time-varying CD4+ cell count and HIV-RNA via inverse probability weighting. Results: Out of 96 562 eligible individuals (78% men) with median (interquantile range) follow-up of 31 [13,65] months, 55 144 initiated cART. The number of cases varied between 898 for tuberculosis and 113 for PML. Compared with non-cART initiation, the hazard ratio (95% confidence intervals) up to 3 months after cART initiation were 1.21 (0.90-1.63) for tuberculosis, 2.61 (1.05-6.49) for MAC, 1.17 (0.34-4.08) for CMV retinitis, 1.18 (0.62-2.26) for PML, 1.21 (0.83-1.75) for HSV, 1.18 (0.87-1.58) for Kaposi sarcoma, 1.56 (0.82-2.95) for NHL, 1.11 (0.56-2.18) for cryptococcosis and 0.77 (0.40-1.49) for candidiasis. Conclusion: With the potential exception of mycobacterial infections, unmasking IRIS does not appear to be a common complication of cART initiation in high-income countries. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins