Objective: To assess the use of two-drug antiretroviral regimens (2DR) and virologic and immunologic outcomes compared with three-drug regimens (3DR) in the EuroSIDA cohort. Design: Multicentre, prospective cohort study. Methods: Logistic regression was used to analyse the uptake and outcomes among HIV-positive individuals who started or switched to a 2DR compared with those on a 3DR. Virologic outcomes were assessed on-treatment as the proportion of individuals with controlled viral load (<400 copies/ml), or with a composite modified FDA snapshot endpoint (mFDA), with mFDA success defined as controlled viral load at 6 months or 12 months for individuals with a known viral load, no regimen changes, AIDS or death. Immunologic response was defined as a 100 cells/mu l or a 25% increase in CD4(+) cell counts from baseline. Results: Between 1 July 2010 and 31 December 2016, 423 individuals started or switched to a 2DR (eight antiretroviral-naive) and 4347 started a 3DR (566 naive). Individuals on 2DR tended to have suppressed viral load, higher CD4(+) cell counts and more comorbidities at baseline compared with those on 3DR. There were no differences in the proportions of individuals who obtained on-treatment or mFDA success, and no significant differences in the adjusted odds ratios for mFDA success or immunologic responses between the 2DR and 3DR groups at 6 months or 12 months. Conclusion: In routine clinical practice, 2DR were largely used for virologically suppressed individuals with higher cumulative exposure to antiretrovirals and comorbidities. Virologic and immunologic outcomes were similar among those on 2DR or 3DR, although confounding by indication cannot be fully excluded due to the observational nature of the study.

A1 Introduction to the 2nd synchronicity forum of GHRI/CHVI-funded Canadian and African HIV prevention and vaccine teams

Background: CD163, a monocyteand macrophage-specific scavenger receptor, is shed as soluble CD163 (sCD163) during the proinflammatory response. Here, we assessed the association of plasma sCD163 levels in HIV-1 infection to AIDS and all-cause mortality. Methods: Plasma sCD163 levels were measured in 933 HIV-1 infected individuals. Hazard ratios (HR) with 95% confidence intervals (95% CI) associated with mortality were computed by Cox proportional hazards regression. Results: At baseline, 86% were on antiretroviral treatment, 73% had plasma HIV RNA < 50 copies/mL and the median CD4 T cell count was 503 cells/μl. During 10.5 years of follow up there were 167 (17.9%) deaths. Plasma sCD163 was higher in non-survivors than in survivors (4.92 mg/L (3.29-8.65) vs. 3.16 mg/L (2.16-4.64), P=0.0001). The cumulative incidence of death increased with increasing plasma sCD163 levels corresponding to a 6% or 35% increased risk of death for each mg/L or quartile increase in baseline plasma sCD163 (adjusted HR: 1.06 (95% CI: 1.03-1.09) and 1.35 (95% CI: 1.13-1.63), respectively). Conclusion: Plasma sCD163 was an independent marker of all-cause mortality in a cohort of HIV-1 infected individuals suggesting that monocyte/macrophage activation may play a role in HIV pathogenesis and be a target of intervention. by Jles L evin on July 1, 2016 http://jidrdjournals.org/ D ow nladed from

Citation for pulished version (APA): Rasmussen, L. J. H., Knudsen, A., Katzenstein, T. L., Gerstoft, J., Obel, N., Rye Jørgensen, N., ... Lebech, A-M. (2016). Soluble urokinase plasminogen activator receptor (suPAR) is a novel, independent predictive marker of myocardial infarction in HIV-1-infected patients: a nested case-control study. HIV Medicine, 17(5), 350–357 . https://doi.org/10.1111/hiv.12315

Background : Impaired renal function is a concern in HIV-infected patients treated with tenofovir. We undertook this study to investigate the prognosis ofrenal function, risk of dialysis and mortality in HIV patients developing moderately reduced renal function while on tenofovir or abacavir. Methods : From a population based cohort of Danish HIV patients, we identified all patients who for the first time had an estimated glomerular filtration rate (eGFR)<50 ml/min per 1.73 m 2 while on tenofovir or abacavir. We calculated median eGFR and the fraction of patients with eGFR<60 ml/min per 1.73 m 2 during followup in the two groups. Cox regression was used to estimate unadjusted and adjusted mortality rate ratios (MRR). Results : We identified 61 patients on tenofovir and 55 on abacavir who developed impaired renal function. Throughout the 2-year study period, the tenofovir group contributed with 87.6 years and the abacavir group with 79.4 years of follow-up. We found no difference between the groups regarding median eGFR or proportions of patients having eGFR <60 ml/min per 1.73 m 2 over time. Five patients in the tenofovir group and two in the abacavir group initiated dialyses within two years after study inclusion. Our study did not indicate that the tenofovir group had increased risk of death (adjusted MRR=0.66, 95% CI: 0.37-1.17). Conclusions : Within the current clinical setting, we were not able to detect a statistical significant difference in renal outcome and mortality between patients developing reduced renal function while on tenofovir or abacavir.

Objectives The objective was to estimate the utilization of psychotropic drugs in HIV ‐infected individuals compared with that in the background population. Methods Using data obtained from the D anish HIV C ohort S tudy and the D anish N ational P rescription R egistry, we analysed aggregated data on redeemed prescription of psychotropic drugs during 1995–2009. We primarily focused our analyses on HIV ‐infected individuals with no history of injecting drug use ( IDU ) or hepatitis C virus ( HCV ) infection. Drug utilization was expressed as defined daily doses per 1000 person‐days ( DDD /1000 PD ). The utilization rate ratio ( URR ) was calculated as utilization in the HIV ‐infected cohort compared with that in the comparison cohort. We estimated longitudinal trends in utilization and potential associations with HIV and exposure to highly active antiretroviral therapy ( HAART ), especially efavirenz. Results During 1995–2009, 54.5% of the HIV ‐infected cohort ( 3615 non‐ IDU /non‐ HCV ‐infected HIV ‐infected individuals) and 29.2% of the comparison cohort (32 535 individuals) had at least one prescription of a psychotropic drug. HIV infection was associated with a URR of 1.13 for antipsychotics, 1.76 for anxiolytics, 4.42 for hypnotics and sedatives, and 2.28 for antidepressants. Antidepressants were confined primarily to men who have sex with men ( MSM ). Older age, more recent calendar time, and increased time after HIV diagnosis were associated with increased drug utilization. However, no association with exposure to HAART or efavirenz was found. Conclusions HIV ‐infected individuals had a higher utilization of psychotropic drugs than the background population, which was not confined to individuals with a history of IDU or HCV infection. This emphasizes the need to focus on diagnosis of, and appropriate psychopharmacological interventions for, mental disorders in this population.

Objectives Recent studies have reported faster progression of HIV infection than anticipated based on results from earlier studies. The aim of the present study was to examine if the virulence of HIV-1 infection changed in the period 1995-2010 among chronically HIV-infected individuals in Denmark. Methods We included all patients registered in the Danish HIV Cohort Study, who were diagnosed in 1995-2009, had a CD4 count >100 cells/L at diagnosis and had at least two CD4 measurements prior to initiation of antiretroviral therapy (ART). Changes in viral set point and rate of CD4 cell decline from enrolment until the initiation of ART by calendar year of HIV diagnosis were analysed. Time to first CD4 count <350 cells/L was compared among patients diagnosed in 1995-2000, 2001-2005 and 2006-2010. Results We followed 1469 HIV-infected patients for a total of 5783 person-years. The median viral set point was 4.27 log10 HIV-1 RNA copies/mL [interquartile range (IQR) 3.58-4.73 log10 copies/mL]. The median CD4 cell decline per year was 57 cells/L (IQR 10-139 cells/L). In analyses adjusted for age, gender, origin, route of transmission and CD4 count at diagnosis, there were no associations between year of diagnosis and viral set point or CD4 cell decline. Time to first CD4 count <350 cells/L did not change in the study period [incidence rate ratio (IRR) 0.90 (95% confidence interval (CI) 0.76-1.06) for 2001-2005 and 1.09 (95% CI 0.79-1.34) for 2006-2010 compared with 1995-2000]. Conclusions We found no evidence of changing trends in viral set point, CD4 cell decline or time to CD4 count <350 cells/L during the period 1995-2010 in a cohort of chronically HIV-infected individuals.

Brucella species are a frequent cause of laboratory-acquired infections. This report describes the handling of a laboratory exposure of 17 laboratory staff members exposed to Brucella melitensis in a large microbiology laboratory in a brucella-non-endemic area. We followed the US Centers for Disease Control and Prevention guidelines, but, of 14 staff members classified as high-risk exposure, none accepted post-exposure prophylaxis. However, in a period of 6 months of follow-up, none of the exposed laboratory workers developed brucellosis and all obtained sera were negative for antibrucella antibodies. We therefore question the value of routine serological follow-up.

Purpose To compare the mortality and causes of death in human immunodeficiency syndrome (HIV) patients with the background population. Methods All adult HIV patients treated in Danish HIV centers from 1995 to 2008 and 14 controls for each HIV patient were included. Age-adjusted mortality rates (MR) and mortality rate ratios (MRR) were estimated using direct standardization and Poisson regression analyses. Up to four contributory causes of death for each person were included in analyses of cause-specific MR. Results A total of 5,137 HIV patients and 71,918 controls were followed for 37,838 and 671,339 person-years (PY), respectively. Among non-injection drug use (IDU) HIV patients, the acquired immune deficiency syndrome (AIDS)-related MR/1,000 PY declined dramatically from 122.9 [95 % confidence interval (CI) 106.8–141.4] in 1995 to 5.0 (95 % CI 3.1–8.1) in 2008. The non-AIDS-related MR did not change substantially from 6.9 (95 % CI 3.8–12.5) to 5.6 (95 % CI 3.6–8.8). The MR of unnatural causes declined from 6.9 (95 % CI 3.8–12.5) to 2.7 (95 % CI 1.4–5.1). The MRR of infections declined from 46.6 (95 % CI 19.6–110.9) to 3.3 (95 % CI 1.6–6.6). The MRR of other natural causes of death remained constant. Conclusions After the introduction of highly active antiretroviral therapy (HAART), the AIDS-related mortality has decreased substantially, but the long-term exposure to HIV and HAART has not translated into increasing mortality from malignancy, cardiovascular, and hepatic diseases.

BackgroundVirological failure of first‐generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) can compromise the efficacy of etravirine as a result of the accumulation of NNRTI resistance mutations. How quickly NNRTI resistance accumulates in patients with a delayed switch from nevirapine or efavirenz despite virological failure, when these drugs are used as a component of combination antiretroviral therapy (cART), remains unclear.MethodsThe rate of NNRTI resistance accumulation was estimated in patients in EuroSIDA with at least two available genotypic resistance tests (GRTs), provided that (1) the date of the first GRT (t0) was after the date of the first virological failure (VF) of an NNRTI, and (2) patients were receiving an NNRTI and HIV RNA was >500 HIV‐1 RNA copies/mL in all measurements between GRTs.ResultsA total of 227 patients were included in the study, contributing 467 GRT pairs. At baseline‐t0, a median of 3 months after VF, 66% of patients had at least one NNRTI mutation: 103N (34%), 181C (22%) and 190A (20%) were the most common mutations. Overall, 180 additional NNRTI mutations were found to have accumulated over 295 years [1 new/1.6 years; 95% confidence interval (CI) 1.5–1.8]. The rate of accumulation was faster in the first 6 months from VF (1 new/1.1 years), and slower in patients exposed to nevirapine vs. those receiving efavirenz [relative risk (RR) 0.66; 95% CI 0.46–0.95; P=0.03].ConclusionsThere is an initial phase of rapid accumulation of NNRTI mutations close to the time of VF followed by a phase of slower accumulation. We predict that it should take approximately one year of exposure to a virologically failing first‐generation NNRTI‐based cART regimen to reduce etravirine activity from fully susceptible to intermediate resistant, and possibly longer in patients kept on a failing nevirapine‐containing regimen.

Objectives Incidence rates (IRs) of Staphylococcus aureus bacteraemia (SAB) are known to be higher in HIV‐infected individuals than in the general population, but have not been assessed in the era of highly active antiretroviral therapy. Methods From 1 January 1995 to 31 December 2007, all Danish HIV‐infected individuals ( n =4871) and population controls ( n =92 116) matched on age and sex were enrolled in a cohort and all cases of SAB were registered. IRs and risk factors were estimated using time‐updated Poisson regression analysis. Results We identified 329 cases of SAB in 284 individuals, of whom 132 individuals were infected with HIV and 152 were not [crude IR ratio (IRR) 24.2; 95% confidence interval (CI) 19.5–30.0, for HIV‐infected vs . non‐HIV‐infected individuals]. Over time, IR declined for HIV‐infected individuals (IRR 0.40). Injecting drug users (IDUs) had the highest incidence and the smallest decline in IR, while men who have sex with men (MSM) had the largest decline over time. Among HIV‐infected individuals, a latest CD4 count <100 cells/μL was the strongest independent predictor of SAB (IRR 10.2). Additionally, HIV transmission group was associated with risk of SAB. MSM were more likely to have hospital‐acquired SAB, a low CD4 cell count and AIDS at the time of HIV acquisition compared with IDUs. Conclusions We found that the incidence of SAB among HIV‐infected individuals declined during the study period, but remained higher than that among HIV‐uninfected individuals. There was an unevenly distributed burden of SAB among HIV transmission groups (IDU>MSM). Low CD4 cell count and IDU were strong predictors of SAB among HIV‐infected individuals.