Incidence and risk factors for invasive pneumococcal disease in HIV-infected and non-HIV-infected individuals before and after the introduction of combination antiretroviral therapy: persistent high risk among HIV-infected injecting drug users.

BACKGROUND: Invasive pneumococcal disease (IPD) is an important cause of morbidity among individuals infected with human immunodeficiency virus (HIV). We described incidence and risk factors for IPD in HIV-infected and uninfected individuals. METHODS: Nationwide population-based cohort study of HIV-infected adults treated at all Danish HIV treatment centers during 1995-2012. Nineteen population-matched controls per HIV-infected individual were retrieved. The risk of IPD was assessed using Poisson regression. RESULTS: The incidence of IPD was 304.7 cases per 100 000 person-years of follow-up (PYFU) in HIV-infected and 12.8 per 100 000 PYFU in HIV-uninfected individuals. After adjusting for confounders, HIV infection (relative risk [RR], 24.4 [95% confidence interval [CI], 23.7-25.1]), male sex (RR, 1.20 [95% CI, 1.16-1.24]), increasing age (per year) (RR, 1.03 [95% CI, 1.03-1.04]), and calendar period (pre-cART RR, 2.80 [95% CI, 2.70-2.91] compared with late cART) were significantly associated with an increased risk of IPD. Among HIV-infected individuals, male sex (RR, 1.57 [95% CI, 1.49-1.66]), smoking (RR, 1.34 [95% CI, 1.26-1.42]), and injecting drug use (RR, 2.51 [95% CI, 2.26-2.67]) were associated with an increased risk of IPD. Detectable viral loads (RR, 1.88 [95% CI, 1.79-1.98]) and a relative fall in CD4 T-cell counts were also associated with an increased risk (≥500 to 350-500 CD4 T cells/µL: RR, 1.29 [95% CI, 1.21-1.37] and <100 cells/µL: RR, 7.4 [95% CI, 6.87-8.02]). The risk of IPD declined over time, although this was not the case for IDUs where the risk remained unchanged. CONCLUSIONS: The incidence of IPD in HIV-infected individuals remained significantly higher than the incidence observed in non-HIV-infected subjects, despite the widespread use of cART. IDUs have a persistently high risk of IPD. Injecting drug use, smoking, and the receipt of cART are suitable targets for preventive measures in the future.

Impact of gender on the risk of AIDS-defining illnesses and mortality in Danish HIV-1-infected patients: a nationwide cohort study.

BACKGROUND: Gender differences in the risk of AIDS-defining illness (ADI) and mortality have been reported in the HIV-1-infected (HIV-positive) population, with conflicting findings. We aimed to assess the impact of gender on the risk of ADI and death in HIV-positive patients infected sexually. METHODS: This was a population-based, nationwide cohort study of incident Danish HIV-positive individuals infected by sexual contact. Outcomes were progression to AIDS and death. We used Cox proportional hazards models and Poisson regression analyses to calculate the risk of progression to AIDS and mortality rate ratios (MRR) between risk groups and compared these with the general Danish population. RESULTS: We identified 587 heterosexually infected women, 583 men who have sex with women (MSW), and 1089 men who have sex with men (MSM). The total follow-up time was 13,708 person-y. At the time of HIV diagnosis MSM had a lower prevalence of AIDS compared to MSW. Women and MSW presented more often with tuberculosis and less often with AIDS-defining cancers compared to MSM. In the adjusted analyses we observed no differences in progression to AIDS. In the adjusted analyses of risk of death, there were no differences between the 3 risk groups, although we saw a trend towards a higher risk of death in older MSW. MSM had a lower risk of death compared to the background population than women and MSW. CONCLUSIONS: In the Danish HIV population, gender has no major impact on progression to AIDS or mortality. Differences in these factors between women, MSW, and MSM are mainly due to confounding from race and CD4 + cell count at diagnosis.

Hepatitis C viral load, genotype 3 and interleukin-28B CC genotype predict mortality in HIV and hepatitis C-coinfected individuals.

OBJECTIVE: We hypothesized that hepatitis C virus (HCV) load and genotype may influence all-cause mortality in HIV-HCV-coinfected individuals. DESIGN AND METHODS: Observational prospective cohort study. Mortality rates were compared in a time-updated multivariate Poisson regression analysis. RESULTS: We included 264 consecutive HIV-HCV-coinfected individuals. During 1143 person years at risk (PYR) 118 individuals died [overall mortality rate 10 (95% confidence interval; 8, 12)/100 PYR]. In multivariate analysis, a 1 log increase in HCV viral load was associated with a 30% higher mortality risk [adjusted mortality rate ratio (aMRR): 1.30 (1.10,1.54)] when adjusted for sex, age, HIV exposure group, CD4 cell count, HIV RNA, HCV genotype and interleukin (IL)-28B genotype. Further, HCV genotype 3 vs. 1 [aMRR: 1.83 (1.12, 2.98)] and HIV RNA [aMRR: 3.14 (1.37,7.17) for undetectable vs. just detectable HIV RNA] were independent predictors of mortality, whereas a higher CD4 cell count was associated with a 41% reduction in mortality rate per 50 cell increase between 0 and 200 cells/µl [aMRR: 0.59 (0.48, 0.72)] and a 10% reduction for increases above 200 cells/µl [aMRR: 0.90 (0.82-0.98)]. IL28B) CC genotype was associated with 54% higher mortality risk [aMRR: 1.54 (0.89, 3.82] compared to TT genotype. CONCLUSION: High-HCV viral load, HCV genotype 3 and IL28B genotype CC had a significant influence on the risk of all-cause mortality among individuals coinfected with HIV-1. This may have consequences for the management of HIV-HCV-coinfected individuals.

[Acute lymphatic leukaemia with eosinophilia in a younger man returning from a travel in the tropics--case report]. / Eosinofil akut lymfatisk leukæmi hos yngre mand hjemvendt fra rejse i troperne.

A 22-year-old man presented with severe back pain and 60% eosinophilia after returning from the tropics. An extensive investigation for parasitic diseases was negative. Over time, his haemoglobin level and thrombocyte count fell, and the spleen and several lymph nodes were enlarged. The patient was diagnosed with acute lymphatic leukaemia with eosinophilia by bone marrow microscopy and flow cytometry. Chromosome analysis detected clonal abnormalities including t(5;14)(q31;q32). He initially responded to chemotherapy, but due to residual disease, he now awaits allogeneic bone marrow transplantation.

Impact of injecting drug use on response to highly active antiretroviral treatment in HIV-1-infected patients: a nationwide population-based cohort study.

The objective of this study was to determine the effect of highly active antiretroviral therapy (HAART) in human immunodeficiency virus (HIV)-infected patients infected through injecting drug use (injecting drug users, IDUs) compared to patients infected via other routes (non-IDUs). We conducted a nationwide population-based cohort study of all HIV-infected patients who initiated HAART during the study period of 1 January 1995 to 31 December 2007. We compared changes in CD4(+) cell counts, percentage of full viral suppression (< 500 copies/ml) and mortality from start of HAART, as well as differences in initial HAART regimen. Three thousand six hundred and fifteen patients were included in the study, representing 22,804 person-y of observation. A total of 346 (9.6%) were categorized as IDUs. Of IDUs, 55% gained full viral control within the first y after HAART compared to 76% of non-IDUs (p = 0.0002). Absolute CD4(+) cell count and survival were lower for IDUs compared to non-IDUs (adjusted mortality rate ratio 3.6 (95% CI 2.9-4.3)). IDUs were more likely to receive a first regimen based on protease inhibitors (PIs) compared to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens for non-IDUs, and IDUs initiated HAART later than non-IDUs. In conclusion, more than half of the HIV-infected patients in Denmark infected through injecting drug use gained full viral suppression after initiating HAART. Absolute CD4(+) cell count was lower and mortality higher among IDUs than non-IDUs.

Signal-averaged P wave duration and the long-term risk of permanent atrial fibrillation.

OBJECTIVE: To assess the long-term risk of developing permanent AF in relation to the signal-averaged P wave duration (SAPWD) and clinical and echocardiographic characteristics. DESIGN: In an observational study design we studied 131 patients with earlier ECG-documented AF and successfully restored sinus rhythm attending a long-term, follow-up visit at hospital or at home. Established permanent AF was examined in relation to primary clinical, echocardiographic, and electrophysiological parameters. RESULTS: Only prolonged SAPWD (p=0.006) was associated with an increased risk of development of permanent AF. The risk of permanent AF after 3 years follow-up was 0.72 with an SAPWD equal to 180 ms versus 0.39 with a normal SAPWD (130 ms). We found no prognostic effect of age, gender, dilated left atrium, long duration of AF history, or long duration of the most recent episode of AF. Co-existing hypertension reduced the risk of permanent AF; this could be explained by concomitant treatment with angiotensin-converting-enzyme-inhibitors. CONCLUSION: Prolonged SAPWD (a marker of atrial remodelling) appears to be a risk factor for long-term development of permanent AF.