Frequency of False Positive Rapid HIV Serologic Tests in African Men and Women Receiving PrEP for HIV Prevention: Implications for Programmatic Roll-Out of Biomedical Interventions

Background

Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.

Methods

We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.

Results

A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.

Conclusions

When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.     

Global environmental change effects on plant community composition trajectories depend upon management legacies

The contemporary state of functional traits and species richness in plant communities depends on legacy effects of past disturbances. Whether temporal responses of community properties to current environmental changes are altered by such legacies is, however, unknown. We expect global environmental changes to interact with land‐use legacies given different community trajectories initiated by prior management, and subsequent responses to altered resources and conditions. We tested this expectation for species richness and functional traits using 1814 survey‐resurvey plot pairs of understorey communities from 40 European temperate forest datasets, syntheses of management transitions since the year 1800, and a trait database. We also examined how plant community indicators of resources and conditions changed in response to management legacies and environmental change. Community trajectories were clearly influenced by interactions between management legacies from over 200 years ago and environmental change. Importantly, higher rates of nitrogen deposition led to increased species richness and plant height in forests managed less intensively in 1800 (i.e., high forests), and to decreases in forests with a more intensive historical management in 1800 (i.e., coppiced forests). There was evidence that these declines in community variables in formerly coppiced forests were ameliorated by increased rates of temperature change between surveys. Responses were generally apparent regardless of sites’ contemporary management classifications, although sometimes the management transition itself, rather than historic or contemporary management types, better explained understorey responses. Main effects of environmental change were rare, although higher rates of precipitation change increased plant height, accompanied by increases in fertility indicator values. Analysis of indicator values suggested the importance of directly characterising resources and conditions to better understand legacy and environmental change effects. Accounting for legacies of past disturbance can reconcile contradictory literature results and appears crucial to anticipating future responses to global environmental change.     

An intraspecific application of the leaf‐height‐seed ecology strategy scheme to forest herbs along a latitudinal gradient

We applied the leaf‐height‐seed (LHS) ecology strategy scheme (a combination of three ecologically important traits: specific leaf area (SLA), seed mass and plant height) intraspecifically to two widespread European forest herbs along a latitudinal gradient. The aims of this study were to quantify LHS trait variation, disentangle the environmental factors affecting these traits and compare the within‐species LHS trait relationships with latitude to previously established cross‐species comparisons. We measured LHS traits in 41 Anemone nemorosa and 44 Milium effusum populations along a 1900–2300 km latitudinal gradient from N France to N Sweden. We then applied multilevel models to identify the effects of regional (temperature, latitude) and local (soil fertility and acidity, overstorey canopy cover) environmental factors on LHS traits. Both species displayed a significant 4% increase in plant height with every degree northward shift (almost a two‐fold plant height difference between the southernmost and northernmost populations). Neither seed mass nor SLA showed a significant latitudinal cline. Temperature had a large effect on the three LHS traits of Anemone. Latitude, canopy cover and soil nutrients were related to the SLA and plant height of Milium. None of the investigated variables appeared to be related to the seed mass of Milium. The variation in LHS traits indicates that the ecological strategy determined by the position of each population in this three‐factor triangle is not constant along the latitudinal gradient. The significant increase in plant height suggests greater competitive abilities for both species in the northernmost populations. We also found that the studied environmental factors affected the LHS traits of the two species on various scales: spring‐flowering Anemone was affected more by temperature, whereas early‐summer flowering Milium was affected more by local and other latitude‐related factors. Finally, previously reported cross‐species correlations between LHS traits and latitude were generally unsupported by our within‐species approach.     

Soil phosphorus availability determines the contribution of small,individual grassland remnants to the conservation of landscape-scale biodiversity

Questions

Small, remnant habitats embedded in degraded, human-dominated landscapes are generally not a priority in conservation, despite their potential role in supporting landscape-scale biodiversity. To warrant their inclusion in conservation management and policy, we question under which conditions they may exhibit the largest conservation value.

Location

Nine landscapes spread across the counties of Stockholm and Södermanland, Sweden.

Methods

Per landscape, plant communities were surveyed in 6 and 12 1 × 1 m² plots across large, intact semi-natural grasslands and small remnant grasslands, respectively. These two contrasting grassland types served as a model system. A topsoil sample was taken in each plot to determine habitat quality in terms of soil pH, plant-available P, and C:N ratio. We used a joint species distribution model to analyse the extent to which grassland type and habitat quality define and predict resident community diversity and composition, including whether they support grassland specialists.

Results

At the landscape scale, the combined remnant grasslands sustained diverse plant communities which did include a significant subset of habitat specialists. Yet, the contribution of individual remnants clearly varied with local-scale habitat quality; soil phosphorus availability lowered plot-level species richness, mostly by constraining the occurrence of grassland specialists. Semi-natural grassland communities were comparatively insensitive to variation in soil phosphorus availability.

Conclusions

The combined habitat amount and the significant number of habitat specialists sustained by remnant grasslands with high habitat quality, shows they can represent a valuable resource to support landscape-scale biodiversity conservation. This offers no wildcard to neglect the continued biotic and abiotic threats on semi-natural grassland plant diversity such as chronic and accumulating P eutrophication, discontinuation of management or poor matrix permeability, as semi-natural grasslands harbour the majority of habitat specialists, while sourcing surrounding remnant grassland communities.

     

Tree diversity is key for promoting the diversity and abundance of forest-associated taxa in Europe

Plant diversity is an important driver of diversity at other trophic levels, suggesting that cascading extinctions could reduce overall biodiversity. Most evidence for positive effects of plant diversity comes from grasslands. Despite the fact that forests are hotspots of biodiversity, the importance of tree diversity, in particular its relative importance compared to other management related factors, in affecting forest-associated taxa is not well known. To address this, we used data from 183 plots, located in different forest types, from Mediterranean to Boreal, and established along a climatic gradient across six European countries (FunDivEUROPE project). We tested the influence of tree diversity, tree functional composition (i.e. functional trait values), forest structure, climate and soil on the diversity and abundance/activity of nine taxa (bats, birds, spiders, microorganisms, earthworms, ungulates, foliar fungal pathogens, defoliating insects and understorey plants) and on their overall diversity and abundance/activity (multidiversity, multiabundance/activity). Tree diversity was a key driver of taxon-level and overall forest-associated biodiversity, along with tree functional composition, forest structure, climate and soil. Both tree species richness and functional diversity (variation in functional trait values) were important. The effects of tree diversity on the abundance/activity of forest-associated taxa were less consistent. Nonetheless, spiders, ungulates and foliar fungal pathogens were all more abundant/active in diverse forests. Tree functional composition and structure were also important drivers of abundance/activity: conifer stands had lower overall multidiversity (although the effect was driven by defoliating insects), while stands with potentially tall trees had lower overall multiabundance/activity. We found more synergies than tradeoffs between diversity and abundance/activity of different taxa, suggesting that forest management can promote high diversity across taxa. Our results clearly show the high value of mixed forest stands for multiple forest-associated taxa and indicate that multiple dimensions of tree diversity (taxonomic and functional) are important.     

Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis

Introduction

Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick “go/no go” decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials.

Methods

The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n = 21) and peripheral SpA with etanercept (cohort 3, n = 20).

Results

Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (−1.26), good for hs-CRP (−0.96) and moderate for MMP-3 (−0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively.

Conclusions

Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA.     

Nutrient input from hemiparasitic litter favors plant species with a fast-growth strategy

Aims

Hemiparasitic plants often produce nutrient-rich litter with high decomposition rates, and thus can enhance nutrient availability. When plant species have differential affinities for this nutrient source, hemiparasitic litter might influence species composition in addition to the parasitic suppression of host species. We expected that species adapted to fertile habitats derive a higher proportion of nutrients from the hemiparasitic litter compared to other species.

Methods

¹⁵N-labeled litter of Rhinanthus angustifolius and Pedicularis sylvatica was added to experimental field plots and adjacent litter bags. We examined N release from the litter, N uptake by the vegetation 2, 4 and 12 months after litter addition and differences in the proportion of N taken up from the litter (N_L) between co-occurring species.

Results

The percentage of N in shoots of co-occurring plant species that is derived from the added hemiparasitic litter (N_L) strongly differed between the species (0.1–6.2 %). After exclusion of species with an alternative N source (legumes as well as ectomycorrhizal and ericoid mycorrhizal species), N_L was positively related (p?<?0.001) with specific leaf area (SLA) and at Pedicularis sites with leaf N concentration (LNC) and leaf phosphorus concentration (LPC) (p?<?0.05), i.e. leaf traits associated with a fast-growth strategy and adaptation to high-nutrient environments.

Conclusions

Our results suggest that nutrient release from hemiparasitic litter favors plant species with a fast-growth strategy adapted to high-nutrient environments compared to species with a slow-growth strategy. Whether continued hemiparasitic litter inputs are able to change species composition in the long term requires further research.