Young people in HIV care in Ukraine: a national survey on characteristics and service provision [version 1; peer review: 2 approved]

Background: Ukraine’s perinatally HIV-infected (PHIV) young people are ageing into adolescence/young adulthood and, alongside those with behaviourally-acquired infections (BHIV), require transitional and other support services. We aimed to map this population and policies/ service provision at specialist HIV centres, to inform future service development. Methods: A national survey was conducted of 28 HIV/AIDS centres on number, characteristics (age group, HIV acquisition mode) and care setting (paediatric/adult) of 10-24 year olds in HIV care in each of 24 regions in January 2016. Information was collected on policies/ service provision at each centre. Results: Of 13,286 young people aged 10-24 years registered for HIV care nationally in Ukraine in January 2016, 1,675 were aged 10-18 years. Three-quarters of ≤19 year olds were PHIV, while 72% of 20-24-year-olds had sexually-acquired infection. Five regions accounted for two-thirds of 10-18 year olds in paediatric and 85% of 19-24 year olds in adult services. In 2015, 97 young people transitioned from paediatric to adult services nationally, typically at 18 years although with flexibility in timing at 17/28 centres. At 27/28 centres, BHIV young people aged <18 years began their HIV care in paediatric services sometimes (5) or always (22). Transition support most commonly consisted of a joint appointment with paediatrician and adult doctor, and support from a psychologist/social worker (both at 24/28 centres). Only 5/28 centres offered routine HIV care during the evening or weekend, and availability of integrated sexual/reproductive health and harm reduction services was uneven. Of 16/28 centres selectively following-up patients who did not attend for care, 15 targeted patients in paediatric services. Conclusions: Heterogeneity in the population and in service availability at the main regional/municipal HIV/ AIDS centres has implications for potential structural barriers to HIV care, and development of services for this group

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment

Background: A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. / Methods: People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody–negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA–negative); or HCV treatment failures (HCV RNA–positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non–acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). / Results: There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1–13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0–6.9) for CVD, 6.5 (95% CI 6.1–6.9) for NADM, and 3.1 (95% CI 2.8–3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14–0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36–1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02–2.13) or treatment failure (aIRR 1.80, 95% CI 1.22–2.66) had significantly raised rates of ESLD, compared to those who were cured. / Conclusions: Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD

Anxiety symptoms and felt stigma among young people living with perinatally or behaviourally-acquired HIV in Ukraine: A cross-sectional survey

BACKGROUND: Ukraine has the second largest European HIV epidemic. This study aimed to describe stigma, demographic and social factors and their association with anxiety among perinatally and behaviourally-HIV-infected (PHIV; BHIV) young people in Kiev and Odessa. METHODS: 104 PHIV and 100 BHIV young people aged 13-25 years completed a confidential tablet-based survey. Survey tools included the Hospital Anxiety and Depression Scale (HADS) (anxiety sub-scale scores of 8-10 indicating mild and ≥11 moderate/severe symptoms in last 7 days), Rosenberg Self-Esteem Scale (RSES) and HIV Stigma Scale (HSS) (short version, composite of disclosure, negative self-image and public attitudes sub-scales). Unadjusted Poisson regression models were fitted to explore factors associated with moderate/severe anxiety symptoms. RESULTS: PHIV and BHIV young people were of median age 15.5 [IQR 13.9-17.1] and 23.0 [21.0-24.3] years, having registered for HIV care a median 12.3 [10.3-14.4] and 0.9 [0.2-2.4] years previously; 97% (97/100) and 66% (65/99) respectively were on ART. Overall 43% (95%CI 36-50%) reported any and 13% (95%CI 9-19%) moderate/severe anxiety symptoms, with no difference by HIV acquisition mode (p = 0.405) or gender (p = 0.700). 42% (75/180) reported history of an emotional health problem for which they had not been referred/attended for care. Moderate/severe anxiety symptoms were associated with HIV-related stigma (prevalence ratio (PR) 1.24 95%CI 1.14-1.34 per HSS unit increase), lower self-esteem (PR 0.83 95%CI 0.78-0.90 per RSES point increase), CD4 ≤350 cells/mm3 (PR 2.29 95%CI 1.06-4.97), having no-one at home who knew the respondent's HIV status (PR 9.15 95%CI 3.40-24.66 vs all know) and, among BHIV, less stable living situation (PR 6.83 95%CI 1.99-23.48 for ≥2 vs no home moves in last 3 years) and history of drug use (PR 4.65 95%CI 1.83-11.85). CONCLUSIONS: Results indicated unmet need for psychosocial support. Further work is needed to explore strategies for mental health support, particularly around disclosure, self-esteem and stigma

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.Peer reviewe

Management of MDR-TB in HIV co-infected patients in Eastern Europe: Results from the TB:HIV study

Objectives Mortality among HIV patients with tuberculosis (TB) remains high in Eastern Europe (EE), but details of TB and HIV management remain scarce. Methods In this prospective study, we describe the TB treatment regimens of patients with multi-drug resistant (MDR) TB and use of antiretroviral therapy (ART). Results A total of 105 HIV-positive patients had MDR-TB (including 33 with extensive drug resistance) and 130 pan-susceptible TB. Adequate initial TB treatment was provided for 8% of patients with MDR-TB compared with 80% of those with pan-susceptible TB. By twelve months, an estimated 57.3% (95%CI 41.5\u201374.1) of MDR-TB patients had started adequate treatment. While 67% received ART, HIV-RNA suppression was demonstrated in only 23%. Conclusions Our results show that internationally recommended MDR-TB treatment regimens were infrequently used and that ART use and viral suppression was well below the target of 90%, reflecting the challenging patient population and the environment in which health care is provided. Urgent improvement of management of patients with TB/HIV in EE, in particular for those with MDR-TB, is needed and includes widespread access to rapid TB diagnostics, better access to and use of second-line TB drugs, timely ART initiation with viral load monitoring, and integration of TB/HIV care

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe

Infection-related and -unrelated malignancies, HIV and the aging population

Funding Information: Conflicts of interest: JR reports personal fees from Abbvie, Bionor, BMS, Boehringer, Gilead, Merck, Janssen, Tobira, Tibotec and ViiV, outside the submitted work. OK has received honoraria, consultancy and/or lecture fees from Abbott, Gilead, GSK, Janssen, Merck, Tibotec and Viiv outside the submitted work. All other authors state no commercial or other associations that may pose a conflict of interest. Funding: Primary support for EuroSIDA is provided by the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), 5th Framework (QLK2-2000-00773), 6th Framework (LSHP-CT-2006-018632) and 7th Framework (FP7/2007?2013; EuroCoord n? 260694) programmes. Current support also includes unrestricted grants from Janssen R&D, Merck and Co. Inc., Pfizer Inc. and GlaxoSmithKline LLC. The participation of centres in Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The authors have no financial disclosures to make. Author contributions: LS developed the project, analysed the data, and was responsible for writing the manuscript. ?HB and OK contributed to the study design and analysis, interpretation of the data and writing of the manuscript. JL proposed the project and contributed to the study design, ideas for analysis, interpretation of the data and writing of the manuscript. BL, PD, AC, JR, BK, JT and IK contributed to national coordination, study design and writing of the manuscript. AM supervised the project and contributed to the study design and analysis, interpretation of the data and writing of the manuscript. Publisher Copyright: © 2016 British HIV AssociationObjectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.publishersversionPeer reviewe

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

Peer reviewe

Multiple Myeloma Treatment in Real-world Clinical Practice : Results of a Prospective, Multinational, Noninterventional Study

Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: The authors would like to thank all patients and their families and all the EMMOS investigators for their valuable contributions to the study. The authors would like to acknowledge Robert Olie for his significant contribution to the EMMOS study. Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc. Funding Information: M.M. has received personal fees from Janssen, Celgene, Amgen, Bristol-Myers Squibb, Sanofi, Novartis, and Takeda and grants from Janssen and Sanofi during the conduct of the study. E.T. has received grants from Janssen and personal fees from Janssen and Takeda during the conduct of the study, and grants from Amgen, Celgene/Genesis, personal fees from Amgen, Celgene/Genesis, Bristol-Myers Squibb, Novartis, and Glaxo-Smith Kline outside the submitted work. M.V.M. has received personal fees from Janssen, Celgene, Amgen, and Takeda outside the submitted work. M.C. reports honoraria from Janssen, outside the submitted work. M. B. reports grants from Janssen Cilag during the conduct of the study. M.D. has received honoraria for participation on advisory boards for Janssen, Celgene, Takeda, Amgen, and Novartis. H.S. has received honoraria from Janssen-Cilag, Celgene, Amgen, Bristol-Myers Squibb, Novartis, and Takeda outside the submitted work. V.P. reports personal fees from Janssen during the conduct of the study and grants, personal fees, and nonfinancial support from Amgen, grants and personal fees from Sanofi, and personal fees from Takeda outside the submitted work. W.W. has received personal fees and grants from Amgen, Celgene, Novartis, Roche, Takeda, Gilead, and Janssen and nonfinancial support from Roche outside the submitted work. J.S. reports grants and nonfinancial support from Janssen Pharmaceutical during the conduct of the study. V.L. reports funding from Janssen Global Services LLC during the conduct of the study and study support from Janssen-Cilag and Pharmion outside the submitted work. A.P. reports employment and shareholding of Janssen (Johnson & Johnson) during the conduct of the study. C.C. reports employment at Janssen-Cilag during the conduct of the study. C.F. reports employment at Janssen Research and Development during the conduct of the study. F.T.B. reports employment at Janssen-Cilag during the conduct of the study. The remaining authors have stated that they have no conflicts of interest. Publisher Copyright: © 2018 The AuthorsMultiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits.publishersversionPeer reviewe

Clinical Outcomes in Persons Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus: Impact of Hepatitis C Virus Treatment.

BACKGROUND A hepatitis C (HCV) cure is associated with changes in lipids and inflammatory biomarkers, but its impact on clinical endpoints among treated human immunodeficiency virus (HIV)/HCV coinfected persons is unclear. METHODS People living with HIV from EuroSIDA with a known HCV status after January 2001 were classified into strata based on time-updated HCV RNA measurements and HCV treatment, as either HCV antibody-negative; spontaneously resolved HCV; chronic, untreated HCV; cured HCV (HCV RNA-negative); or HCV treatment failures (HCV RNA-positive). Poisson regression was used to compare incidence rates between HCV groups for end-stage liver disease (ESLD; including hepatocellular carcinoma [HCC]), non-acquired immunodeficiency virus defining malignancy (NADM; excluding HCC), and cardiovascular disease (CVD). RESULTS There were 16 618 persons included (median follow-up 8.3 years, interquartile range 3.1-13.7). There were 887 CVD, 902 NADM, and 436 ESLD events; crude incidence rates/1000 person-years follow-up were 6.4 (95% confidence interval [CI] 6.0-6.9) for CVD, 6.5 (95% CI 6.1-6.9) for NADM, and 3.1 (95% CI 2.8-3.4) for ESLD. After adjustment, there were no differences in incidence rates of NADM or CVD across the 5 groups. HCV-negative individuals (adjusted incidence rate ratio [aIRR] 0.22, 95% CI 0.14-0.34) and those with spontaneous clearance (aIRR 0.61, 95% CI 0.36-1.02) had reduced rates of ESLD compared to cured individuals. Persons with chronic, untreated HCV infections (aIRR 1.47, 95% CI 1.02-2.13) or treatment failure (aIRR 1.80, 95% CI 1.22-2.66) had significantly raised rates of ESLD, compared to those who were cured. CONCLUSIONS Incidences of NADM or CVD were independent of HCV group, whereas those cured had substantially lower incidences of ESLD, underlining the importance of successful HCV treatment for reducing ESLD