Liver stiffness and virologic outcomes after introducing tenofovir as part of antiretroviral therapy in lamivudine-experienced adults with HIV and hepatitis B virus (HBV) co-infection in Ghana: four-year follow up of the prospective HEPIK cohort

Introduction Until recently lamivudine was the only available agent to treat hepatitis B in the context of HIV infection in sub‐Saharan Africa. Tenofovir is gradually becoming available although access remains far from universal. Long‐term outcomes of introducing tenofovir as part of antiretroviral therapy (ART) in subjects previously extensively exposed to lamivudine as the sole HBV‐active agent in the region are unknown. Methods We report from a prospective cohort of HIV/HBV co‐infected adults attending for HIV care in Kumasi, Ghana, where HBsAg prevalence is 14%. HBsAg‐positive subjects were invited to attend for transient elastography (TE) and blood sampling before the introduction of tenofovir (TO) as part of ART, and within 1 year (T1) and 4 years (T2) of starting tenofovir. Adherence and alcohol consumption were determined by a questionnaire‐based interview. Results Overall 178 patients underwent evaluation at T0/T1, of whom 98 (55%) also attended for assessment at T2. Remaining patients were lost to follow up (50; 28%); had died (10; 6%); declined to attend (17; 10%); or were excluded due to pregnancy (2; 1 %) or invalid TE (1; 1 %). Of the 98 subjects, 94 had started tenofovir‐based ART and had received tenofovir for median 4 years (IQR 3.8, 4.1), while continuing previous lamivudine (Table 1). By multivariable linear regression, female gender, no history of alcohol excess, and higher HBV DNA level, higher liver stiffness, and lower platelet count at T0/T1 were significant predictors of decreasing liver stiffness between TO/1 and T2. No treatment‐emergent resistance mutations in HBV polymerase were observed by Sanger sequencing among subjects with HBV DNA>100 lU/ml at T2; one subject showed M204V+V173L+L180M at both TO and T2. Conclusions This is the first report of the long‐term impact on liver stiffness and virologic parameters of introducing tenofovir as part of ART in extensively lamivudine exposed HIV/HBV co‐infected patients in sub‐Saharan Africa. Significant reductions in liver stiffness and improved HBV control were observed at four years

Outcomes of COVID-19 related hospitalization among people with HIV in the ISARIC WHO Clinical Characterization Protocol (UK): a prospective observational study

BACKGROUND: Evidence is conflicting about how HIV modulates COVID-19. We compared the presentation characteristics and outcomes of adults with and without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the ISARIC WHO CCP study. METHODS: We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, ten individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy). RESULTS: Among 47,592 patients, 122 (0.26%) had confirmed HIV infection and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 versus 74 years; p<0.001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive vs. HIV-negative groups (26.7% vs. 32.1%; p=0.16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; p<0.001 [log-rank test]). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.01-2.14; p=0.05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; p=0.008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; p<0.001). CONCLUSIONS: HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19

Hepatitis B vaccination impact and the unmet need for antiviral treatment in Blantyre, Malawi

BACKGROUND: Hepatitis B is the leading cause of cirrhosis and liver cancer in sub-Saharan Africa. To reduce hepatitis-associated mortality, antiviral treatment programmes are needed. We estimated prevalence, vaccine impact and need for antiviral treatment in Blantyre, Malawi to inform an effective public health response. METHODS: We conducted a household study in Blantyre in 2016-2018. We selected individuals from a census using random sampling and estimated age-sex-standardised HBsAg seroprevalence. Impact of infant hepatitis B vaccination, which began in 2002, was estimated by binomial log-linear regression comparing individuals born before and after vaccine implementation. In HBsAg-positive adults, eligibility for antiviral therapy was assessed. RESULTS: Of 97,386 censused individuals, 6,073 (median age 18 years; 56.7% female) were sampled. HBsAg seroprevalence was 5.1% (95% CI 4.3-6.1) among adults and 0.3% (0.1-0.6) among children born after vaccine introduction. Estimated vaccine impact was 95.8% (70.3-99.4). Of HBsAg-positive adults, 26% were HIV-positive. Among HIV-negative individuals, 3%, 6% and 9% were eligible for hepatitis B treatment by WHO, European and American hepatology association criteria, respectively. CONCLUSIONS: Infant HBV vaccination has been highly effective in reducing HBsAg prevalence in urban Malawi. Up to 9% of HBsAg-positive HIV-negative adults are eligible, but have an unmet need, for antiviral therapy

Organic Farming Improves Pollination Success in Strawberries

Pollination of insect pollinated crops has been found to be correlated to pollinator abundance and diversity. Since organic farming has the potential to mitigate negative effects of agricultural intensification on biodiversity, it may also benefit crop pollination, but direct evidence of this is scant. We evaluated the effect of organic farming on pollination of strawberry plants focusing on (1) if pollination success was higher on organic farms compared to conventional farms, and (2) if there was a time lag from conversion to organic farming until an effect was manifested. We found that pollination success and the proportion of fully pollinated berries were higher on organic compared to conventional farms and this difference was already evident 2–4 years after conversion to organic farming. Our results suggest that conversion to organic farming may rapidly increase pollination success and hence benefit the ecosystem service of crop pollination regarding both yield quantity and quality

Benthic pH gradients across a range of shelf sea sediment types linked to sediment characteristics and seasonal variability

This study used microelectrodes to record pH profiles in fresh shelf sea sediment cores collected across a range of different sediment types within the Celtic Sea. Spatial and temporal variability was captured during repeated measurements in 2014 and 2015. Concurrently recorded oxygen microelectrode profiles and other sedimentary parameters provide a detailed context for interpretation of the pH data. Clear differences in profiles were observed between sediment type, location and season. Notably, very steep pH gradients exist within the surface sediments (10–20 mm), where decreases greater than 0.5 pH units were observed. Steep gradients were particularly apparent in fine cohesive sediments, less so in permeable sandier matrices. We hypothesise that the gradients are likely caused by aerobic organic matter respiration close to the sediment–water interface or oxidation of reduced species at the base of the oxic zone (NH4+, Mn2+, Fe2+, S−). Statistical analysis suggests the variability in the depth of the pH minima is controlled spatially by the oxygen penetration depth, and seasonally by the input and remineralisation of deposited organic phytodetritus. Below the pH minima the observed pH remained consistently low to maximum electrode penetration (ca. 60 mm), indicating an absence of sub-oxic processes generating H+ or balanced removal processes within this layer. Thus, a climatology of sediment surface porewater pH is provided against which to examine biogeochemical processes. This enhances our understanding of benthic pH processes, particularly in the context of human impacts, seabed integrity, and future climate changes, providing vital information for modelling benthic response under future climate scenarios

An empirical model for probabilistic decadal prediction: global attribution and regional hindcasts

Empirical models, designed to predict surface variables over seasons to decades ahead, provide useful benchmarks for comparison against the performance of dynamical forecast systems; they may also be employable as predictive tools for use by climate services in their own right. A new global empirical decadal prediction system is presented, based on a multiple linear regression approach designed to produce probabilistic output for comparison against dynamical models. A global attribution is performed initially to identify the important forcing and predictor components of the model . Ensemble hindcasts of surface air temperature anomaly fields are then generated, based on the forcings and predictors identified as important, under a series of different prediction ‘modes’ and their performance is evaluated. The modes include a real-time setting, a scenario in which future volcanic forcings are prescribed during the hindcasts, and an approach which exploits knowledge of the forced trend. A two-tier prediction system, which uses knowledge of future sea surface temperatures in the Pacific and Atlantic Oceans, is also tested, but within a perfect knowledge framework. Each mode is designed to identify sources of predictability and uncertainty, as well as investigate different approaches to the design of decadal prediction systems for operational use. It is found that the empirical model shows skill above that of persistence hindcasts for annual means at lead times of up to 10 years ahead in all of the prediction modes investigated. It is suggested that hindcasts which exploit full knowledge of the forced trend due to increasing greenhouse gases throughout the hindcast period can provide more robust estimates of model bias for the calibration of the empirical model in an operational setting. The two-tier system shows potential for improved real-time prediction, given the assumption that skilful predictions of large-scale modes of variability are available. The empirical model framework has been designed with enough flexibility to facilitate further developments, including the prediction of other surface variables and the ability to incorporate additional predictors within the model that are shown to contribute significantly to variability at the local scale. It is also semi-operational in the sense that forecasts have been produced for the coming decade and can be updated when additional data becomes available