Prevention and Treatment of Hepatitis B Virus Infection in HIV-Infected Patients

We describe in a multicenter study the feasibility and effectiveness of an accelerated hepatitis B vaccination schedule compared to the standard regimen in HIV-infected patients. The results show that the compliance with an accelerated schedule is significantly better, although its efficacy is only non-inferior in patients with a CD4+ cell-count >500 cells/mm3. In all HIV-infected patients a better response rate is provided in patients on HAART with undetectable HIV-RNA load, longer duration of HAART use, female gender and younger age. Around 50% of our HIV-infected cohort responded on initial HBV vaccination. In an attempt to achieve a higher response rate we prospectively revaccinated all non-responders three times at monthly intervals with double dose HBV vaccine. An additional 51% responded in the revaccination series. This response was more likely in patients younger than 40 years of age, irrespective of viral load, while in patients older than 40 years an undetectable HIV-RNA load is associated with a better response rate. We studied the possible relationship between HBV and influenza vaccination in HIV-infected patients. A trend for higher geometric mean titers, both in pre- and post- influenza immunization was found in HBV vaccination responders. We also retrospectively investigated the long-term efficacy of tenofovir administered as a part of antiretroviral therapy in a large cohort of HIV/HBV co-infected patients. It is shown that after five years of follow-up, approximately 90% of patients achieved undetectable HBV-DNA load. There was no significant difference between patients with or without lamivudine resistance at baseline. Furthermore, no confirmed genotypic substitutions in the HBV polymerase gene associated with decreased sensitivity to tenofovir have been identified in our cohort

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

A prospective open study of the efficacy of high-dose recombinant hepatitis B rechallenge vaccination in HIV-infected patients

Double-dose hepatitis B virus revaccination of human immunodeficiency virus (HIV) -infected patients proved to be effective in 50.7% of 144 patients who had previously failed to respond to standard doses. In the multivariate analysis, female patients were found to have a significantly better response (P = .03). The effect of age on the response depended on the viral load at the time of revaccination. For patients with a detectable HIV RNA load, the effect of age was stronger (odds ratio [ OR], 0.34 per 10 years older [ 95% confidence interval {CI}, 0.16-0.72]; P = .005) than for patients with an undetectable HIV RNA load (OR, 0.74 per 10 years older [ 95% CI, 0.50-1.09]; P = .12)