Patient-reported outcomes in the single-tablet regimen (STaR) trial of rilpivirine/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate in antiretroviral treatment-naive adults infected with HIV-1 through 48 weeks of treatment.

This 96-week, randomized, open-label study was designed to assess the efficacy and safety of two single-tablet regimens in treatment naïve HIV-1-infected adults: rilpivirine (RPV) + emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) and efavirenz (EFV) + FTC/TDF. Assessments included patient-reported Medication Adherence Self-Report Inventory, SF-12v2 Quality of Life assessment, HIV Treatment Satisfaction Questionnaire, and HIV Symptom Index Questionnaire through Week 48. Additional evaluations included study drug discontinuations due to treatment-emergent adverse events (TEAEs). A total of 786 participants (n=394 RPV/FTC/TDF, n=392 EFV/FTC/TDF) were included. Fewer RPV/FTC/TDF-treated than EFV/FTC/TDF-treated participants discontinued study drug due to TEAEs (2.5% vs. 8.7%), with 41% (14/34) TEAE-related discontinuations in the EFV/FTC/TDF group occurring within the first four weeks of treatment. Treatment adherence and satisfaction remained high through Week 48 and quality of life improved from baseline in both groups. There were no significant between-group differences in virologic success (HIV-1 RNA <50 copies/mL) regardless of adherence (<95% or ≥95%). Significant between-group differences favouring RPV/FTC/TDF were observed for the HIV SIQ symptoms of difficulty falling or staying asleep (p = .022) and diarrhea or loose bowel movements (p = .002). In conclusion, 48-week treatment with RPV/FTC/TDF or EFV/FTC/TDF was associated with high adherence, high treatment satisfaction, and improved quality of life. TEAE-related discontinuations and patient-reported symptoms indicate that RPV/FTC/TDF may be somewhat better tolerated than EFV/FTC/TDF.

Systematic Review: The Effectiveness of Interventions to Reduce Falls and Improve Balance in Adults With Multiple Sclerosis.

OBJECTIVES: To evaluate the effectiveness of interventions in reducing falls and/or improving balance as a falls risk in multiple sclerosis (MS). DATA SOURCES: Computer-based and manual searches included the following medical subject heading keywords: "Multiple Sclerosis AND accidental falls" OR "Multiple Sclerosis AND postural balance" OR "Multiple Sclerosis AND exercise" OR "Multiple Sclerosis AND physical/physio therapy" NOT animals. All literature published to November 2014 with available full-text details were included. STUDY SELECTION: Studies were reviewed against the PICO (participants, interventions, comparisons, outcomes) selection criteria: P, adults with MS; I, falls management/balance rehabilitation interventions; C, randomized/quasi-randomized studies comparing intervention with usual care or placebo control; O, falls outcomes and measures of balance. Fifteen articles of the original 529 search results were included. DATA EXTRACTION: Two reviewers independently extracted data and assessed methodological quality using the Cochrane Risk of Bias tool. DATA SYNTHESIS: Random-effects meta-analysis indicated a small decrease in falls risk (risk ratio, .74), although the 95% confidence interval (CI) crossed 1 (95% CI, .12-4.38). The pooled standardized mean difference (SMD) for balance outcomes was .55 (95% CI, .35-.74). SMD varied significantly between exercise subgroupings; gait, balance, and functional training interventions yielded the greatest pooled effect size (ES) (SMD=.82; 95% CI, 0.55-1.10). There was a moderate positive correlation between program volume (min/wk) and ES (Cohen's d) (r=.70, P=.009), and a moderate negative correlation between program duration in weeks and ES (r=-.62, P=.03). Variations in interventions and outcomes and methodological limitations mean that results must be viewed with caution. CONCLUSIONS: This review suggests that balance may improve through exercise interventions, but that the magnitude of the improvements achieved in existing programs may not be sufficient to impact falls outcomes. Supporting participants to achieve an appropriate intensity of practice of highly challenging balance activities appears to be critical to maximizing effectiveness.

Frequency, characteristics, and consequences of falls in multiple sclerosis: findings from a cohort study.

OBJECTIVE: To evaluate falls rate and the characteristics of falls (including fall-related injuries) in a multiple sclerosis (MS) cohort. DESIGN: As part of a study evaluating falls risk, a cohort of 150 participants prospectively recorded actual and near fall events using a daily diary over 3 months, as well as the circumstances of each fall including related injuries. SETTING: Community setting. PARTICIPANTS: A population-based sample of people (N=150) with a confirmed diagnosis of MS (Expanded Disability Status Scale, 3.5-6.5) was recruited via a patient-centered longitudinal study database of disease course in people with MS. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Rate of actual and near falls, circumstances and consequences of falls (including rates and type of injury plus follow-up care). RESULTS: The response rate for the falls diary was 92.7%. A total of 672 actual falls and 3785 near falls were recorded, with a moderate correlation between the numbers of actual and near falls per person (ρ=.474; 95% confidence interval, .34-.59). Men recorded significantly more falls than women. Falls were associated with a range of activities, although 27.6% occurred during general mobility activities such as walking, turning, and moving between positions. Injuries occurred in 11.1% of falls, with 6 individuals requiring medical attention. CONCLUSIONS: People with MS experience high numbers of falls, with associated injuries. Falls occur during a wide range of activities, reflecting their potential impact on daily life. Evaluating the characteristics of individuals who experience frequent near falls but few actual falls may be valuable for research and clinical practice.

Global validation of data-assimilative electron ring current nowcast for space weather applications.

The hazardous plasma environment surrounding Earth poses risks to satellites due to internal charging and surface charging effects. Accurate predictions of these risks are crucial for minimizing damage and preparing for system failures of satellites. To forecast the plasma environment, it is essential to know the current state of the system, as the accuracy of the forecast depends on the accuracy of the initial condition of the forecast. In this study, we use data assimilation techniques to combine observational data and model predictions, and present the first global validation of a data-assimilative electron ring current nowcast during a geomagnetic storm. By assimilating measurements from one satellite and validating the results against another satellite in a different magnetic local time sector, we assess the global response and effectiveness of the data assimilation technique for space weather applications. Using this method, we found that the simulation accuracy can be drastically improved at times when observations are available while eliminating almost all of the bias previously present in the model. These findings contribute to the construction of improved operational models in estimating surface charging risks and providing realistic 'source' populations for radiation belt simulations.

Risk factors for falls in multiple sclerosis: an observational study.

BACKGROUND: People with multiple sclerosis (MS) experience frequent falls, which are associated with impairments and limitations to activities and participations. OBJECTIVE: The objective of this paper is to evaluate falls risk factors using robust clinical measures. METHODS: A total of 150 individuals (confirmed MS diagnosis, Expanded Disability Status Scale (EDSS) 3.5-6.5) were recruited, with 148 participants included in the final analysis. Demographic data were collected and performance assessed in eight predictor measures (Physiological Profile Assessment (PPA), Brief Ataxia Rating scale, Ashworth scale (Ashworth), Modified Falls Efficacy scale, Symbol Digit Modalities Test, dual-task interference, lying/standing blood pressure, static/dynamic visual acuity). Participants prospectively recorded falls over three months using a daily diary. People were classified as "fallers" based on reports of ≥ two falls. RESULTS: A total of 104 participants recorded 672 falls; 78 (52.7%) reported ≥ two falls. Continence issues, previous falls history and use of prescribed medications were each associated with increased risk of being a "faller". Ashworth and PPA risk score contributed significantly to a logistic regression model predicting faller/non-faller classification. The reduced model (Ashworth, PPA, EDSS) showed fair-to-good predictive ability (ROC c-statistic 0.73, sensitivity 70%, specificity 69%). CONCLUSION: This study confirms the high prevalence of falls in ambulant people with MS. Important potentially modifiable risk factors are identified, suggesting aspects to target in falls interventions.

A missing dusk-side loss process in the terrestrial electron ring current.

The Earth's magnetic field traps charged particles which are transported longitudinally around Earth, generating a near-circular current, known as the ring current. While the ring current has been measured on the ground and space for many decades, the enhancement of the ring current during geomagnetic storms is still not well understood, due to many processes contributing to its dynamics on different time scales. Here, we show that existing ring current models systematically overestimate electron flux observations of 10-50 keV on the nightside during storm onset. By analyzing electron drift trajectories, we show that this systematic overestimation of flux can be explained through a missing loss process which operates in the pre-midnight sector. Quantifying this loss reveals that the theoretical upper limit of loss has to be reached over a broad region of space in order to reproduce the observations. This missing loss may be attributed to inaccuracies in the parameterization of the loss due to chorus wave interactions, combined with the scattering by electrostatic electron cyclotron harmonic waves which is currently not included in ring current models.

Similar But Different: Integrated Phylogenetic Analysis of Austrian and Swiss HIV-1 Sequences Reveal Differences in Transmission Patterns of the Local HIV-1 Epidemics.

OBJECTIVES: Phylogenetic analyses of 2 or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics. METHODS: A maximum-likelihood phylogenetic tree was built using pol -sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: (1) domestic cherries; (2) international cherries; and (3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared with the respective distribution expected from a random distribution of patients on the phylogeny. RESULTS: The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. Although international cherries in the SHCS were dominated by heterosexuals with men who have sex with men being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user and the other one non-intravenous drug user were underrepresented. CONCLUSIONS: In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by men who have sex with men in the AHIVOS, and by heterosexuals in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV.

The effect of closed-kinetic chain exercises and open-kinetic chain exercise on the muscle activity of vastus medialis oblique and vastus lateralis.

Patellofemoral pain syndrome (PFPS) is one of the most prevalent musculoskeletal conditions of the lower limb. The muscle imbalance between the vastus medialis oblique (VMO) and vastus lateralis (VL) muscles is one of the main factors leading to the development of PFPS. The disparity in research and the necessity to add to the existing literature base led to the development of this study. The aim of this study was to investigate the effect of 2 closed kinetic chain exercises and 1 open kinetic chain exercise on VMO and VL muscle activity. Twenty-two healthy asymptomatic individuals participated in this study. The surface electromyography (EMG) of VMO and VL was measured and used to calculate the VMO:VL ratio during 3 different quadriceps-strengthening exercises (a double leg squat with isometric hip adduction exercise, an open kinetic chain knee extension exercise, and a lunge exercise). The double leg squat with isometric hip adduction exercise was shown to produce a significantly greater VMO:VL ratio (1.14:1) than the other 2 exercises (p = 0.015 and p = 0.005). The open kinetic chain knee extension exercises produced significantly greater activation of VL than the lunge exercise (p = 0.001 and p = 0.036). The lunge exercise produced the VMO:VL ratio (1.18:1) closest to the idealized ratio of 1:1. Potential clinical recommendations can be made proposing the lunge exercise as a key tool in early rehabilitation when restoring preferential VMO:VL ratio is essential. The double leg squat with isometric hip adduction exercise would be useful in maintaining correct patella tracking and selectively strengthening VMO.

Experiences of people with Parkinson's disease and their views on physical activity interventions: a qualitative systematic review.

OBJECTIVE: The objective of the review was to synthesize the best available qualitative evidence on the experiences and preferences of people with Parkinson's disease for physical activity, their perceived motivators and barriers to engagement, as well as their views on support mechanisms and behavior change interventions designed to sustain participation. INTRODUCTION: National and international guidelines recommend regular physical activity to improve health and wellbeing and to prevent disease. Research on Parkinson's disease indicates that physical activity programs can be beneficial in addressing both physical symptoms and overall wellbeing. However, despite recommendations, sustained engagement in regular physical activity among people with Parkinson's disease is limited. To promote physical activity it is important to understand their perspectives on this topic. INCLUSION CRITERIA: This review considered studies that included a qualitative evaluation of the experiences and views of people with Parkinson's disease regarding physical activity and interventions designed to sustain participation. METHODS: The databases MEDLINE, Embase, CINAHL, AMED, Scopus and Web of Science, and unpublished studies in sources of grey literature (Google, OpenGrey, MedNar, Conference Paper Index, PQDT) were searched. Language limiters were restricted to English and dates ranged from the inception of the database to June 30, 2017. Two reviewers assessed studies that met the inclusion criteria independently, using the criteria of the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Qualitative Research. One reviewer completed data extraction using the standardized qualitative data extraction tool. This was checked for accuracy by a second reviewer. The qualitative research findings were pooled using JBI methodology. The JBI process of meta-aggregation was used to identify categories and synthesized findings. RESULTS: Nineteen studies were included in this review following assessment of the methodological quality of each study. Two studies were excluded after the methodological review as the findings were not supported by illustrations of the participant voice. Subsequently, 105 findings were extracted and aggregated into 20 categories and eight synthesized findings. Methodological quality was variable and overall confidence in the findings was determined to be low. CONCLUSION: This review revealed that people with Parkinson's disease viewed physical activity as an enjoyable and positive experience, which aided with control of their symptoms and enhanced their wellbeing and quality of life. Aligned with evidence from older adults and those with long-term conditions, this review identified disease presentation, intrapersonal characteristics, program design, external support and the social and physical environment as contributory factors which influenced the ability of people with Parkinson's disease to sustain engagement in physical activity. The unique contribution and weighting of these factors will affect an individual's participation in physical activity. This review provides important insights into the challenges of undertaking physical activity while living with a progressive and fluctuating disease. These qualitative findings give healthcare providers an insight into the views and experiences of people with Parkinson's disease and are useful, alongside quantitative evidence of effectiveness, for the design of physical activity programs that are meaningful for this population. However, a limitation of this review is that it does not address the views and experiences of people with Parkinson's disease who are inactive.

The reliability and validity of the L-test in people with Parkinson's disease.

OBJECTIVE: To evaluate the test-retest and concurrent validity of the L-test in a group of participants with mild to moderate Parkinson's disease. The L-test is an extended version of the Timed up and Go test, incorporating a longer walking distance and turns in two directions. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: 16 participants (13 male), mean age 75 (SD 6.7) mean duration since diagnosis 7.1 years (±2.8). Disease severity was mild to moderate on the Hoehn and Yahr scale (mean 2.1; mode 2; range 1-3). 14 participants (12 male) completed the study. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A Bland and Altman plot examined the agreement between first and second testing occasion of the L-test. Intra-class correlation coefficients (ICC) assessed the test-retest reliability. Concurrent validity was established by correlating the L-test with the Timed up and Go test (TUG). The Minimal Detectable Change with 95% confidence interval (MDC95) was calculated to determine the true change not due to chance. RESULTS: The L-test showed excellent test-retest reliability on the Bland & Altman plot and the ICC. There was a high degree of agreement between measurements taken on days 1 and 2. The L-test correlated strongly with the Timed up and Go test on both measurement days with r=0.97 (p<0.001) and r=0.96 (p<0.001). The MDC95 was 5.31seconds. CONCLUSIONS: The L-test is a reliable and valid outcome measurement for the assessment of walking ability in participants with mild to moderate Parkinson's disease.

Single-measurement therapeutic drug monitoring of the HIV/AIDS drugs abacavir, zidovudine, lamivudine, efavirenz, nevirapine, lopinavir and nelfinavir.

BACKGROUND: There is currently no consensus about the significance of therapeutic drug monitoring (TDM) in the management of human immunodeficiency virus (HIV) infection. OBJECTIVES: In this study, single drug levels from routine clinical samples were determined in order to add further data on the therapeutic plasma level range and on drug levels under anti-HIV therapy in general. MATERIALS AND METHODS: A total of 215 plasma samples obtained from patients with HIV infection for whom TDM was requested for the first time were evaluated. Plasma values were determined for abacavir and zidovudine between 1 and 3 h after drug intake. Lamivudine, efavirenz, nevirapine, lopinavir and nelfinavir plasma values were determined between 1 and 12 h after drug intake. Drug levels were determined with a home-brewed assay based on high-performance liquid chromatography. RESULTS: Plasma concentrations of HIV drugs showed a large variability. Plasma concentrations of abacavir, zidovudine and lamivudine were found to be similar to those reported recently. For efavirenz and nevirapine, 37 and 61% of the samples did not meet the minimum trough levels suggested. For lopinavir and nelfinavir, the majority of the samples (78 and 80%) were found to be within the therapeutic plasma level range. CONCLUSION: Despite a large variation of anti-HIV drug plasma concentrations, single-measurement TDM may be sufficient in the routine management of the majority of patients.

Development of a balance, safe mobility and falls management programme for people with multiple sclerosis.

PURPOSE: To utilise stakeholder input to inform the structure, format and approach of a multiple sclerosis (MS) balance, safe mobility and falls management programme. MATERIALS AND METHODS: Using a three-round nominal group technique, participants individually rated their agreement with 20 trigger statements, followed by a facilitated group discussion and re-rating. Three mixed groups included service users (n = 15) and providers (n = 19). Quantitative analysis determined agreement, whilst qualitative responses were analysed thematically. RESULTS: Median scores for each of the 20 trigger statements did not change significantly over sequential rounds, however, deviations around the medians indicated more agreement amongst participants over time. Key recommendations were: Aims and approach: The programme should be tailored to the needs of people with MS. Falls and participation-based outcomes are equally important. Structure and format: The programme should balance expected burden and anticipated benefit, moving away from models requiring weekly attendance and promoting and supporting self-efficacy. Optimising engagement: Support to maintain engagement and intensity of practice over the long term is essential. Sustainability: Adequate funding is necessary. Staff should have MS specific knowledge and experience. CONCLUSIONS: Participants collaboratively identified critical components of a MS balance, safe mobility and falls management programme. They also highlighted the importance of a collaborative, user-centred, MS-specific approach. Implications for Rehabilitation People with multiple sclerosis need condition-specific interventions focussed on maximising balance and safe mobility and reducing falls. Programme design should support self-efficacy and flexible engagement. Adequate support and funding are seen as essential by both service users and providers.

Experiences of people with Parkinson's disease and their views of physical activity interventions: a qualitative systematic review protocol.

REVIEW QUESTION/OBJECTIVES: This review aims to explore the experiences of people with Parkinson's disease (pwPD) participation in physical activity and their views of interventions designed to engage and sustain engagement. Synthesis of the best available evidence will be used to determine any gaps in the research literature and make recommendations on approaches to increase and maintain engagement in physical activity in pwPD living in a community setting. The specific objectives are to.

First identification of a recombinant form of hepatitis C virus in Austrian patients by full-genome next generation sequencing.

Hepatitis C virus (HCV) intergenotypic recombinant forms have been reported for various HCV genotypes/subtypes in several countries worldwide. In a recent study, four patients living in Austria had been identified to be possibly infected with a recombinant HCV strain. To clarify results and determine the point of recombination, full-genome next-generation sequencing using the Illumina MiSeq v2 300 cycle kit (Illumina, San Diego, CA, USA) was performed in the present study. Samples of all of the patients contained the recombinant HCV strain 2k/1b. The point of recombination was found to be within the HCV NS2 gene between nucleotide positions 3189-3200 based on H77 numbering. While three of four patients were male and had migration background from Chechnya (n = 2) and Azerbaijan (n = 1), the forth patient was a female born in Austria. Three of the four patients including the female had intravenous drug abuse as a risk factor for HCV transmission. While sequencing techniques are limited to a few specialized laboratories, a genotyping assay that uses both ends of the HCV genome should be employed to identify patients infected with a recombinant HCV strain. The correct identification of recombinant strains also has an impact considering the tailored choice of anti-HCV treatment.

Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results.

In 2 double-blind phase 3 trials, 1733 antiretroviral-naive adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95% confidence interval: 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P < 0.001), with no cases of proximal tubulopathy for TAF vs 4 for TDF. There were greater increases in lipids with TAF vs TDF, with no difference in the total cholesterol to high-density lipoprotein ratio. For initial HIV therapy, E/C/F/TAF is superior to E/C/F/TDF in efficacy and bone and renal safety.

A Single Quantifiable Viral Load Is Predictive of Virological Failure in Human Immunodeficiency Virus (HIV)-Infected Patients on Combination Antiretroviral Therapy: The Austrian HIV Cohort Study.

Background. Viral loads (VLs) detectable at low levels are not uncommon in patients on combination antiretroviral therapy (cART). We investigated whether a single quantifiable VL predicted virological failure (VF). Methods. We analyzed patients receiving standard regimens with at least 1 VL measurement below the limit of quantification (BLQ) in their treatment history. The first VL measurement after 6 months of unmodified cART served as baseline VL for the subsequent analyses of the time to reach single VL levels of ≥200, ≥400, and ≥1000 copies/mL. Roche TaqMan 2.0 was used to quantify human immunodeficiency virus-1 ribonucleic acid. Factors associated with VF were determined by Cox proportional hazards models. Results. Of 1614 patients included in the study, 68, 44, and 34 experienced VF ≥200, ≥400, and ≥1000 copies/mL, respectively. In multivariable analyses, compared with patients who were BLQ, a detectable VL ≤ 50 and VL 51-199 copies/mL predicted VF ≥ 200 copies/mL (hazards ratio [HR] = 2.19, 95% confidence interval [CI] = 1.06-4.55 and HR = 4.21, 95% CI = 2.15-8.22, respectively). In those with VL 51-199 copies/mL, a trend for an increased risk of VF ≥400 and VF ≥1000 copies/mL could be found (HR = 2.13, 95% CI = 0.84-5.39 and HR = 2.52, 95% CI = 0.96-6.60, respectively). Conclusions. These findings support closer monitoring and adherence counseling for patients with a single measurement of quantifiable VL <200 copies/mL.

Characterization of HIV Transmission in South-East Austria.

To gain deeper insight into the epidemiology of HIV-1 transmission in South-East Austria we performed a retrospective analysis of 259 HIV-1 partial pol sequences obtained from unique individuals newly diagnosed with HIV infection in South-East Austria from 2008 through 2014. After quality filtering, putative transmission linkages were inferred when two sequences were ≤1.5% genetically different. Multiple linkages were resolved into putative transmission clusters. Further phylogenetic analyses were performed using BEAST v1.8.1. Finally, we investigated putative links between the 259 sequences from South-East Austria and all publicly available HIV polymerase sequences in the Los Alamos National Laboratory HIV sequence database. We found that 45.6% (118/259) of the sampled sequences were genetically linked with at least one other sequence from South-East Austria forming putative transmission clusters. Clustering individuals were more likely to be men who have sex with men (MSM; p<0.001), infected with subtype B (p<0.001) or subtype F (p = 0.02). Among clustered males who reported only heterosexual (HSX) sex as an HIV risk, 47% clustered closely with MSM (either as pairs or within larger MSM clusters). One hundred and seven of the 259 sequences (41.3%) from South-East Austria had at least one putative inferred linkage with sequences from a total of 69 other countries. In conclusion, analysis of HIV-1 sequences from newly diagnosed individuals residing in South-East Austria revealed a high degree of national and international clustering mainly within MSM. Interestingly, we found that a high number of heterosexual males clustered within MSM networks, suggesting either linkage between risk groups or misrepresentation of sexual risk behaviors by subjects.

Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

BACKGROUND: In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV) and virological failure (VF) under combined antiretroviral therapy (cART). MATERIALS AND METHODS: We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL) measurement below the quantification limit (BLQ) in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥ 200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models. RESULTS: Of 2276 participants, 1972 (86.6%) were BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI): 4.19 (2.07-8.49); for 10.000-99.999 copies/mL: aOR (95% CI): 2.52 (1.23-5.19)] and shorter cART duration [for <9 months: aOR (95% CI): 2.59 (1.38-4.86)]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI): 2.76 (1.03-7.35); for 30-50 years: aOR (95% CI): 2.70 (1.26-5.79)], people originating from high prevalence countries [aOR (95% CI): 2.20 (1.09-4.42)] and in male injecting drug users [aOR (95% CI): 2.72 (1.38-5.34)]. CONCLUSIONS: For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.

Difference in factors associated with low-level viraemia and virological failure: results from the Austrian HIV Cohort Study.

INTRODUCTION: For some patients, it remains a challenge to achieve complete virological suppression which is the goal of antiretroviral therapy (ART). Identifying factors associated with low-level viraemia (LLV) and virological failure (VF) under ART might help to optimize management of these patients. MATERIALS AND METHODS: We investigated patients from the Austrian HIV Cohort Study receiving unmodified ART for >6 months with two nucleoside reverse-transcriptase inhibitors (NRTIs) with either a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) or an integrase inhibitor (INSTI) between 1 July 2012 and 1 July 2013 with at least one viral load (VL) measurement below the limit of detection (BLD) or below level of quantification (BLQ) in their treatment history. VF was defined as HIV-RNA levels ≥200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLD and BLQ were identified by using logistic regression models. RESULTS: Of the 2,276 patients analyzed, 1,972 (86.6%) were BLD or BLQ, 222 (9.8%) showed LLV and 82 (3.6%) had VF. A higher risk for LLV and VF was found in patients with ART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from a centre which uses Abbott RealTime HIV-1 assay compared to the other centres measuring VL by the Roche Cobas AmpliPrep/Cobas TaqMan 2.0. A higher risk for LLV but not for VF was found in patients with a higher VL before ART and shorter ART duration. A higher risk for VF but not for LLV was found in patients of younger age, originating from a high prevalence country, with a lower CD4 count and in male injecting drug users. CONCLUSIONS: This study of well-defined patients on stable ART over a period of more than six months gives insights into the different factors associated with LLV and VF. In patients with VF, factors associated with adherence play a prominent role, whereas in patients with LLV, the biology of viral replication comes additionally into effect. Despite its observational design, it has implications for patient management and forms the basis for future outcome studies.

Treatment modification in HIV-Infected individuals starting antiretroviral therapy between 2011 and 2014.

INTRODUCTION: While antiretroviral therapy (ART) has increased the survival of HIV patients and turned HIV infection into a chronic condition, treatment modifications and poor adherence might limit this therapeutic success. METHODS: Patients from the Austrian HIV Cohort Study, who started their first ART after Rilpivirine became available in February 2011, were analyzed for factors associated with treatment modification which could be either a change of drugs or a stop of the regimen. A drug was considered as stopped when the regimen was interrupted for more than eight days. Drugs of particular interest were Darunavir (DRV), Atazanavir (ATV), Raltegravir (RAL), Rilpivirine (RPV) and Efavirenz (EFV). RPV and EFV were analyzed only when taken as single tablet regimen. Other drugs were summarized as "other." Proportional hazards regression methods were used to identify predictors of discontinuation and Kaplan-Meier estimates were used to calculate probabilities of discontinuation. Patients who died were censored at the date of death. RESULTS: 965 patients started ART, 282 with DRV, 161 with ATV, 96 with RAL, 108 with RPV and 118 with EFV. Median time for taking initial ART is 11.6 months. 322 (33.4%) patients modified their initial ART. The overall probability of modification at one year was 28.7%, at two years 40.0% and at three years 49.8%. In a multivariable proportional hazards regression analysis, AIDS diagnosis at baseline and injecting drug use (IDU) of men compared with men who have sex with men (MSM) have a higher risk of switch/stop. Compared with DRV, RPV showed a much lower and ATV and particularly "other" a higher risk for discontinuation (Table 1). CONCLUSION: Rates of modification and interruption were still high in recent years, particularly in the first year of ART. The decreased rate of modification found in patients treated with Rilpivirine may be attributed to selection of patients according to guidelines.