Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

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

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Early green narratives and the rise of bioregionalism : an ecocritical perspective on British fiction, 1880-1920

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

A systematic review of the effectiveness and cost-effectiveness of peer-based interventions to maintain and improve offender health in prison settings

Background: Offender health is deemed a priority issue by the Department of Health. Peer support is an established feature of prison life in England and Wales; however, more needs to be known about the effectiveness of peer-based interventions to maintain and improve health in prison settings. Objectives: The study aimed to synthesise the evidence on peer-based interventions in prison settings by carrying out a systematic review and holding an expert symposium. Review questions were (1) what are the effects of peer-based interventions on prisoner health and the determinants of prisoner health?, (2) what are the positive and negative impacts on health services within prison settings of delivering peer-based interventions?, (3) how do the effects of peer-based approaches compare with those of professionally led approaches? and (4) what are the costs and cost-effectiveness of peer-based interventions in prison settings? Data sources: For the systematic review, 20 electronic databases including MEDLINE, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature and EMBASE were searched from 1985. Grey literature and relevant websites were also searched. To supplement the review findings 58 delegates, representing a variety of organisations, attended an expert symposium, which provided contextual information. Review methods: Two reviewers independently selected studies using the following inclusion criteria: population – prisoners resident in prisons and young offender institutions; intervention – peer-based interventions; comparators: review questions 3 and 4 compared peer-led and professionally led approaches; outcomes – prisoner health or determinants of health, organisational/process outcomes or views of prison populations; study design: quantitative, qualitative and mixed-methods evaluations. Two reviewers extracted data and assessed validity using piloted electronic forms and validity assessment criteria based on published checklists. Results from quantitative studies were combined using narrative summary and meta-analysis when appropriate; results from qualitative studies were combined using thematic synthesis. Results: A total of 15,320 potentially relevant papers were identified of which 57 studies were included in the effectiveness review and one study was included in the cost-effectiveness review; most were of poor methodological quality. A typology of peer-based interventions was developed. Evidence suggested that peer education interventions are effective at reducing risky behaviours and that peer support services provide an acceptable source of help within the prison environment and have a positive effect on recipients; the strongest evidence came from the Listener scheme. Consistent evidence from many predominantly qualitative studies suggested that being a peer deliverer was associated with positive effects across all intervention types. There was limited evidence about recruitment of peer deliverers. Recurring themes were the importance of prison managerial and staff support for schemes to operate successfully, and risk management. There was little evidence on the cost-effectiveness of peer-based interventions. An economic model, developed from the results of the effectiveness review, although based on data of variable quality and a number of assumptions, showed the cost-effectiveness of peer-led over professionally led education in prison for the prevention of human immunodeficiency virus (HIV) infection. Limitations: The 58 included studies were, on the whole, of poor methodological quality. Conclusions: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health. Peer support services can also provide an acceptable source of help within the prison environment and can have a positive effect on recipients. This was confirmed by expert evidence. Research into cost-effectiveness is sparse but a limited HIV-specific economic model, although based on a number of assumptions and evidence of variable quality, showed that peer interventions were cost-effective compared with professionally led interventions. Well-designed intervention studies are needed to provide robust evidence including assessing outcomes for the target population, economic analysis of cost-effectiveness and impacts on prison health services. More research is needed to examine issues of reach, utilisation and acceptability from the perspective of recipients and those who choose not to receive peer support. Study registration: This study was registered as PROSPERO CRD42012002349. Funding: The National Institute for Health Research Health Services and Delivery Research programme

Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

International audienceBackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.ResultsAmong 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.ConclusionsIn virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes