Predictors of virological failure among people living with HIV receiving first line antiretroviral treatment in Myanmar: retrospective cohort analysis.

BACKGROUND: Progress toward the global target for 95% virological suppression among those on antiretroviral treatment (ART) is still suboptimal. We describe the viral load (VL) cascade, the incidence of virological failure and associated risk factors among people living with HIV receiving first-line ART in an HIV cohort in Myanmar treated by the Médecins Sans Frontières in collaboration with the Ministry of Health and Sports Myanmar. METHODS: We conducted a retrospective cohort study, including adult patients with at least one HIV viral load test result and having received of at least 6 months' standard first-line ART. The incidence rate of virological failure (HIV viral load ≥ 1000 copies/mL) was calculated. Multivariable Cox's regression was performed to identify risk factors for virological failure. RESULTS: We included 25,260 patients with a median age of 33.1 years (interquartile range, IQR 28.0-39.1) and a median observation time of 5.4 years (IQR 3.7-7.9). Virological failure was documented in 3,579 (14.2%) participants, resulting in an overall incidence rate for failure of 2.5 per 100 person-years of follow-up. Among those who had a follow-up viral load result, 1,258 (57.1%) had confirmed virological failure, of which 836 (66.5%) were switched to second-line treatment. An increased hazard for failure was associated with age ≤ 19 years (adjusted hazard ratio, aHR 1.51; 95% confidence intervals, CI 1.20-1.89; p < 0.001), baseline tuberculosis (aHR 1.39; 95% CI 1.14-1.49; p < 0.001), a history of low-level viremia (aHR 1.60; 95% CI 1.42-1.81; p < 0.001), or a history of loss-to-follow-up (aHR 1.24; 95% CI 1.41-1.52; p = 0.041) and being on the same regimen (aHR 1.37; 95% CI 1.07-1.76; p < 0.001). Cumulative appointment delay was not significantly associated with failure after controlling for covariates. CONCLUSIONS: VL monitoring is an important tool to improve programme outcomes, however limited coverage of VL testing and acting on test results hampers its full potential. In our cohort children and adolescents, PLHIV with history of loss-to-follow-up or those with low-viremia are at the highest risk of virological failure and might require more frequent virological monitoring than is currently recommended.

Does community-wide water chlorination reduce hepatitis E virus infections during an outbreak? A geospatial analysis of data from an outbreak in Am Timan, Chad (2016-2017).

Hepatitis E Virus (HEV) genotype 1 and 2 infect an estimated 20 million people each year, via the faecal-oral transmission route. An urban outbreak of HEV occurred in Am Timan, Chad, between September 2016 and April 2017. As part of the outbreak response, Médecins Sans Frontières and the Ministry of Health implemented water and hygiene interventions, including the chlorination of town water sources. We aimed to understand whether these water treatment activities had any impact on the number of HEV infections, using geospatial analysis of epidemiological and water treatment monitoring data. By conducting cluster analysis we investigated whether there were areas of particularly high and low infection risk during the outbreak and explored the reasons for this. We observed two high-risk spatial clusters of suspected cases and one high-risk cluster of confirmed cases. Our main finding was that confirmed HEV cases had a higher median number of days of exposure to unsafe water compared to suspected and non-confirmed cases (Kruskal-Wallis Chi Square: 15.5; p < 0.001). Our study confirms the mixed, but shifting, transmission routes during this outbreak. It also highlights the spatial and temporal analytical methods, which can be employed in future outbreaks to improve understanding of HEV transmission.

Learning from water treatment and hygiene interventions in response to a hepatitis E outbreak in an open setting in Chad.

In September 2016, Médecins Sans Frontières responded to a hepatitis E (HEV) outbreak in Chad by implementing water treatment and hygiene interventions. To evaluate the coverage and use of these interventions, we conducted a cross-sectional study in the community. Our results showed that 99% of households interviewed had received a hygiene kit from us, aimed at improving water handling practice and personal hygiene and almost all respondents had heard messages about preventing jaundice and handwashing. Acceptance of chlorination of drinking water was also very high, although at the time of interview, we were only able to measure a safe free residual chlorine level (free chlorine residual (FRC) ≥0.2 mg/L) in 43% of households. Households which had refilled water containers within the last 18 hours, had sourced water from private wells or had poured water into a previously empty container, were all more likely to have a safe FRC level. In this open setting, we were able to achieve high coverage for chlorination, hygiene messaging and hygiene kit ownership; however, a review of our technical practice is needed in order to maintain safe FRC levels in drinking water in households, particularly when water is collected from multiple sources, stored and mixed with older water.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Associations between national viral hepatitis policies/programmes and country-level socioeconomic factors: a sub-analysis of data from the 2013 WHO viral hepatitis policy report.

BACKGROUND: As more countries worldwide develop national viral hepatitis strategies, it is important to ask whether context-specific factors affect their decision-making. This study aimed to determine whether country-level socioeconomic factors are associated with viral hepatitis programmes and policy responses across WHO Member States (MS). METHODS: WHO MS focal points completed a questionnaire on national viral hepatitis policies. This secondary analysis of data reported in the 2013 Global Policy Report on the Prevention and Control of Viral Hepatitis in WHO Member States used logistic regression to examine associations between four survey questions and four socioeconomic factors: country income level, Human Development Index (HDI), health expenditure and physician density. RESULTS: This analysis included 119 MS. MS were more likely to have routine viral hepatitis surveillance and to have a national strategy and/or policy/guidelines for preventing infection in healthcare settings if they were in the higher binary categories for income level, HDI, health expenditure and physician density. In multivariable analyses, the only significant finding was a positive association between having routine surveillance and being in the higher binary HDI category (adjusted odds ratio 26; 95% confidence interval 2.0-340). CONCLUSION: Countries with differing socioeconomic status indicators did not appear to differ greatly regarding the existence of key national policies and programmes. A more nuanced understanding of the multifaceted interactions of socioeconomic factors, health policy, service delivery and health outcomes is needed to support country-level efforts to eliminate viral hepatitis.

Are the testing needs of key European populations affected by hepatitis B and hepatitis C being addressed? A scoping review of testing studies in Europe.

AIM: To investigate whether or not key populations affected by hepatitis B and hepatitis C are being tested sufficiently for these diseases throughout the European region. METHODS: We searched MEDLINE and EMBASE for studies on HBV and HCV testing in the 53 Member States of the World Health Organization European Region following PRISMA criteria. RESULTS: 136 English-language studies from 24 countries published between January 2007 and June 2013 were found. Most studies took place in 6 countries: France, Germany, Italy, the Netherlands, Turkey, and the United Kingdom. 37 studies (27%) addressed HBV, 46 (34%) HCV, and 53 (39%) both diseases. The largest categories of study populations were people who use drugs (18%) and health care patient populations (17%). Far fewer studies focused on migrants, prison inmates, or men who have sex with men. CONCLUSIONS: The overall evidence base on HBV and HCV testing has considerable gaps in terms of the countries and populations represented and validity of testing uptake data. More research is needed throughout Europe to guide efforts to provide testing to certain key populations.

Shigellosis in refugees, Austria, July to November 2015.

We report on a cluster of shigellosis including 21 cases in refugees and two in local residents who worked in refugee transit centres, detected in Austria in 2015, between calendar weeks 29 and 47. The species isolated from the cluster cases, including one mixed infection, were S. sonnei (n = 13), S. flexneri (n = 10) and S. boydii (n = 1). Eleven of 18 tested isolates were extended spectrum beta-lactamase (ESBL)-positive, including five of six ciprofloxacin-resistant and three azithromycin-resistant isolates.

Policy responses to viral hepatitis B and C among people who inject drugs in Member States of the WHO European region: a sub-analysis of the WHO 2013 global hepatitis policy survey.

BACKGROUND: Unsafe injections, through infectious bodily fluids, are a major route of transmission for hepatitis B and C. Viral hepatitis burden among people who inject drugs is particularly high in many Member States of central and Eastern Europe while national capacity and willingness to address it varies greatly. METHODS: The initial survey included 43 questions covering awareness, data, prevention, and screening and treatment. It was sent in five languages to identified national focal points. This sub-analysis included 11 questions and 53 Member States in the WHO European Region. Descriptive analyses of national activities are presented. As a secondary outcome bivariate analyses of differences between Member States of the European Union (EU) and European Free Trade Association (EFTA) compared to those not in said grouping are presented. RESULTS: Forty-four of the 53 Member States responded to the survey (response rate of 83%). More than three-quarters reported offering publicly-funded treatment for HBV or HCV (82% and 80%, respectively), with a significantly higher proportion of EU/EFTA Member States (P=0.004 and P=0.010, respectively). Half of Member States (53%) reported the existence of a national policy for hepatitis prevention and control; however less than one-third (27%) reported having written national strategies. Under half of the responding Member States reported holding events for World Hepatitis Day 2012. One-fifth reported offering hepatitis B and C testing free of charge, with less than one-third reportedly conducting regular serosurveys among people who inject drugs. CONCLUSIONS: Findings highlight key gaps requiring attention in order to improve national policies and programmes in the region and ensure an adequate response to injection drug use-associated viral hepatitis. Further studies are required to assess quality and impact of national policies and services.

Correction: Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

[This corrects the article DOI: 10.1371/journal.pone.0271910.].

Advanced HIV disease and associated attrition after re-engagement in HIV care in Myanmar from 2003 to 2019: a retrospective cohort study.

BACKGROUND: The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known. METHODS: We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition. RESULTS: Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU. CONCLUSIONS: Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.

Viraemic-time predicts mortality among people living with HIV on second-line antiretroviral treatment in Myanmar: A retrospective cohort study.

INTRODUCTION: Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar. METHODS: We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories. RESULTS: Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20-49%, and 50-79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30-3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11-4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12-2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50-79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21-7.10, p = 0.02 and aHR 2.71, 95% CI 1.22-6.01, p = 0.01). This association was not observed in those with viraemic-time <50%. CONCLUSIONS: Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.

A large outbreak of Hepatitis E virus genotype 1 infection in an urban setting in Chad likely linked to household level transmission factors, 2016-2017.

BACKGROUND: In September 2016, three acutely jaundiced (AJS) pregnant women were admitted to Am Timan Hospital, eastern Chad. We described the outbreak and conducted a case test-negative study to identify risk factors for this genotype of HEV in an acute outbreak setting. METHODS: Active case finding using a community based surveillance network identified suspected AJS cases. Pregnant or visibly ill AJS cases presenting at hospital were tested with Assure® IgM HEV rapid diagnostic tests (RDTs) and some with Polymerase Chain Reaction (PCR) in Amsterdam; confirmed cases were RDT-positive and controls were RDT-negative. All answered questions around: demographics, household makeup, area of residence, handwashing practices, water collection behaviour and clinical presentation. We calculated unadjusted odds ratios (ORs) and 95% confidence intervals (95% CI). RESULTS: Between September and April 2017, 1443 AJS cases (1293 confirmed) were detected in the town(attack rate: 2%; estimated 65,000 population). PCR testing confirmed HEV genotype 1e. HEV RDTs were used for 250 AJS cases; 100 (40%) were confirmed. Risk factors for HEV infection, included: having at least two children under the age of 5 years (OR 2.1, 95%CI 1.1-4.3), having another household member with jaundice (OR 2.4, 95%CI 0.90-6.3) and, with borderline significance, living in the neighbourhoods of Riad (OR 3.8, 95%CI 1.0-1.8) or Ridina (OR 3.3, 95%CI 1.0-12.6). Cases were more likely to present with vomiting (OR 3.2, 9%CI 1.4-7.9) than controls; possibly due to selection bias. Cases were non-significantly less likely to report always washing hands before meals compared with controls (OR 0.33, 95%CI 0.1-1.1). DISCUSSION: Our study suggests household factors and area of residence (possibly linked to access to water and sanitation) play a role in HEV transmission; which could inform future outbreak responses. Ongoing sero-prevalence studies will elucidate more aspects of transmission dynamics of this virus with genotype 1e.

Anthropometric indices and selenium status in British adults: the U.K. National Diet and Nutrition Survey.

Recent studies have raised concern over possible associations between high selenium (Se) status and excess adiposity, known to be linked to adverse cardiometabolic outcomes. Studies of Se status in relation to adiposity are scarce in the United Kingdom. This study examined cross-sectional associations of anthropometric indices with Se-status biomarkers in a nationally representative sample of 1045 (577 female, 468 male) British Caucasian adults ages 19-64 who participated in the 2000-2001 National Diet and Nutrition Survey. Median (first, third quartile) values for whole-blood glutathione peroxidase (GPx) activity and plasma and erythrocyte Se concentrations were 120.0 (103.0, 142.4) nmol mg Hb(-1) min(-1), 1.08 (0.98, 1.20) µmol/L, and 1.62 (1.38, 1.91) µmol/L, respectively. For males, values were 119.0 (100.0, 141.0) nmol mg Hb(-1) min(-1), 1.09 (0.99, 1.22) µmol/L, and 1.54 (1.34, 1.79) µmol/L, respectively; for females 121.0 (105.0, 145.0) nmol mg Hb(-1) min(-1), 1.07 (0.97, 1.18) µmol/L, and 1.71 (1.43, 1.99) µmol/L, respectively. Multivariate adjusted mean differences (95% CI) in whole-blood GPx between the highest (>30 kg/m(2)) and the lowest (<25 kg/m(2)) categories of body mass index and the highest (96.5-139.2 cm) and the lowest (52.2-78.1cm) quartiles of waist circumference (WC) were -7.9 (-13.2, -2.7) and -9.7 (-16.2, -3.2) nmol mg Hb(-1) min(-1), respectively. Difference (95% CI) in plasma Se between the third (87.5-96.4 cm) and the lowest quartiles of WC was -0.04 (-0.08, -0.03) µmol/L. Difference (95% CI) in red blood cell (RBC) Se between the highest (0.91-1.11) and the lowest (0.53-0.76) quartiles of waist-to-hip ratio (WHR) was 0.10 (0.00, 0.20) µmol/L. Similar results were observed in gender and menopausal-status subgroup analyses. The inverse association between plasma Se and WC and the positive association between RBC Se and WHR will need confirmation. The findings suggest associations between low whole-blood GPx activity and higher measures of general and central adiposity. Further experimental and randomized studies are needed to deduce the mechanisms and infer causality.