Participants on Dolutegravir Resuppress Human Immunodeficiency Virus RNA After Virologic Failure: Updated Data from the ADVANCE Trial.

Following evidence of HIV RNA re-suppression on DTG-based regimens, we assess the re-suppressive capacity of ADVANCE participants on TAF/FTC+DTG, TDF/FTC+DTG, and TDF/FTC/EFV. Viraemic participants were able to re-suppress within 3 follow-up visits of protocol-defined virological failure (PDVF) in 77/121 (64%), 85/126 (67%), and 44/138 (32%) cases respectively (DTG regimens vs. TDF/FTC/EFV; P < 0.001).

Risk Factors for Bud Perennation of Podosphaera macularis on Hop.

The hop powdery mildew fungus Podosphaera macularis persists from season to season in the Pacific Northwestern United States through infection of crown buds because only one of the mating types needed to produce the ascigerous stage is presently found in this region. Bud infection and successful overwintering of the fungus leads to the emergence of heavily infected shoots in early spring (termed flag shoots). Historical data of flag shoot occurrence and incidence in Oregon and Washington State during 2000 to 2017 were analyzed to identify their association with the incidence of powdery mildew, growers' use of fungicides, autumn and winter temperature, and other production factors. During this period, flag shoots were found on 0.05% of plants evaluated in Oregon and 0.57% in Washington. In Oregon, the incidence of powdery mildew on leaves was most severe and the number of fungicide applications made by growers greatest in yards where flag shoots were found in spring. Similarly, the incidence of plants with powdery mildew in Washington was significantly associated with the number of flag shoots present in early spring, although the number of fungicide applications made was independent of flag shoot occurrence. The occurrence of flag shoots was associated with prior occurrence of flag shoots in a yard, the incidence of foliar powdery mildew in the previous year, grower pruning method, and, in Washington, winter temperature. A census of hop yards in the eastern extent of the Oregon production region during 2014 to 2017 found flag shoots in 27 of 489 yards evaluated. In yards without flag shoots, 338 yards (73.2%) were chemically pruning or not pruned, whereas the remaining 124 (26.8%) were mechanically pruned. Of the 27 yards with flag shoots, 22 were either chemically pruned or not pruned and 4 were mechanically pruned in mid-April, well after the initial emergence of flag shoots. The prevalence of yards with flag shoots also was related to thoroughness of pruning in spring (8.1% of yards with incomplete pruning versus 1.9% of yards with thorough pruning). A Bayesian logistic regression model was fit to the data from the intensively assessed yards in Oregon, with binary risk factors for occurrence of a flag shoot in the previous year, occurrence of foliar mildew in the previous year, and thoroughness of pruning in spring. The model indicated that the median and 95% highest posterior density interval of the probability of flag shoot occurrence was 0.0008 (0.0000 to 0.0053) when a yard had no risk factors but risk increased to 0.0065 (0.0000 to 0.0283) to 0.43 (0.175 to 0.709) when one to all three of the risk factors were present. The entirety of this research indicates that P. macularis appears to persist in a subset of chronically affected hop yards, particularly yards where spring pruning is conducted poorly. Targeted management of the disease in a subset of fields most at risk for producing flag shoots could potentially influence powdery mildew development regionwide.

Susceptibility of Hop Crown Buds to Powdery Mildew and its Relation to Perennation of Podosphaera macularis.

In the Pacific Northwestern United States, the hop powdery mildew fungus, Podosphaera macularis, survives overwintering periods in association with living host tissue because the ascigerious stage of the pathogen is not known to occur in this region. Field experiments were conducted over a 5-year period to describe the overwintering process associated with crown bud infection and persistence of P. macularis. Surface crown buds increased in abundance and size beginning in early July and continuing until mid-September. Buds of varying sizes remained susceptible to powdery mildew until late September to early October in each of 3 years of experiments, with susceptibility decreasing substantially thereafter. Potted plants were inoculated sequentially during early summer to autumn, then evaluated in the following year for development of shoots colonized by the powdery mildew fungus (termed flag shoots) due to bud perennation. Emergence of flag shoots was asynchronous and associated with shoot emergence and elongation. Flag shoots emerged over a protracted period from late February to early June, year dependent. In all 4 years of experiments, some infected buds broke and produced flag shoots after chemical desiccation of shoots in spring, a common horticultural practice in hop production conducted to set training timing and eliminate initial inoculum. Flag shoots were most numerous when plants were inoculated with P. macularis in early summer and, consequently, when powdery mildew was present throughout the entire period of crown bud development. The number of flag shoots produced was reduced from 6.8- to 46.6-fold when comparing the latest versus earliest inoculation dates. However, all inoculation timings yielded flag shoots at some level, suggesting that bud infection that occurs over an extended period of time in the previous season may allow the fungus to perennate. In studies in two commercial hop yards in Washington State, fungicide applications made after harvest reduced the level of powdery mildew on leaves in the current year but did not significantly reduce flag shoots in the following year. Given that bud infection occurred over a 10-week period, flag shoots developed even when plants were exposed to inoculum in October and some flag shoots survived chemical pruning practices, management efforts seem best directed to both preventative measures to reduce the likelihood of bud infection and remedial practices to physically eliminate infected crown buds in the ensuing year.

Pre- and Postinfection Activity of Fungicides in Control of Hop Downy Mildew.

Optimum timing and use of fungicides for disease control are improved by an understanding of the characteristics of fungicide physical mode of action. Greenhouse and field experiments were conducted to quantify and model the duration of pre- and postinfection activity of fungicides most commonly used for control of hop downy mildew (caused by Pseudoperonospora humuli). In greenhouse experiments, control of downy mildew on leaves was similar among fungicides tested when applied preventatively but varied depending on both the fungicide and the timing of application postinfection. Disease control decreased as applications of copper were made later after inoculation. In contrast, cymoxanil, trifloxystrobin, and dimethomorph reduced disease with similar efficacy when applied 48 h after inoculation compared with preventative applications of these fungicides. When fungicides were applied 72 h after inoculation, only dimethomorph reduced the sporulating leaf area similarly to preinoculation application timing. Adaxial chlorosis, necrosis, and water soaking of inoculated leaves, indicative of infection by P. humuli, were more severe when plants were treated with cymoxanil, trifloxystrobin, and dimethomorph 48 to 72 h after inoculation, even though sporulation was suppressed. Trifloxystrobin and dimethomorph applied 72 h after inoculation suppressed formation of sporangia on sporangiophores as compared with all other treatments. In field studies, dimethomorph, fosetyl-Al, and trifloxystrobin suppressed development of shoots with systemic downy mildew to the greatest extent when applied near the timing of inoculation, although the duration of preventative and postinfection activity varied among the fungicides. There was a small reduction in efficacy of disease control when fosetyl-Al was applied 6 to 7 days after inoculation as compared with protective applications. Trifloxystrobin had 4 to 5 days of preinfection activity and limited postinfection activity. Dimethomorph had the longest duration of protective activity. Percent disease control was reduced progressively with increasing time between inoculation and application of dimethomorph. These findings provide guidance to the use of fungicides when applications are timed with forecasted or post hoc disease hazard warnings, as well as guidance on tank-mixes of fungicides that may be suitable both for resistance management considerations and extending intervals between applications.

Association of Spring Pruning Practices with Severity of Powdery Mildew and Downy Mildew on Hop.

Downy mildew (caused by Pseudoperonospora humuli) and powdery mildew (caused by Podosphaera macularis) are important diseases of hop in the Pacific Northwest United States, and cultural practices may affect the severity of both diseases. The association of spring pruning quality and timing with severity of downy mildew and powdery mildew was assessed through analysis of survey data collected from commercial hop yards in Oregon and Washington. Among 149 hop yards surveyed, the most common pruning method was chemical desiccation (48% of yards), mechanical pruning (23%), or a combination of these practices (15%). The quality of pruning was assessed using a three-category ordinal scale ("excellent", "moderate", or "poor") based on the amount of foliage remaining on plants following pruning. Excellent pruning quality was attained more often in yards pruned twice (74.6 to 82.1% of yards) versus once (33.8% of yards), independent of pruning method. Seasonal severity of downy mildew in Oregon increased approximately twofold with reduction in pruning quality from excellent to moderate to poor. Pruning quality was not significantly related to levels of powdery mildew on leaves or cones in Oregon. Under more severe disease pressure in Washington, however, seasonal severity of powdery mildew on leaves and the incidence of cones with powdery mildew were significantly greater in yards that had poor pruning compared with excellent pruning. Moreover, yards that had excellent pruning quality received, on average, 1.1 to 1.5 fewer fungicide applications per season for downy mildew or powdery mildew compared with yards that had moderate or poor pruning quality. This savings was associated with delayed initiation of the first application by 7.5 to 14.2 days in yards with excellent pruning quality. Replicated experiments in commercial yards in Oregon quantified the effect of delaying pruning timing 5 to 21 days compared with growers' standard practices on the diseases and yield. Downy mildew suppression by delayed pruning was dependent on cultivar and year of sampling, being significantly reduced fivefold only in 'Willamette' in 2007. Severity of powdery mildew and cone yield was similar between plots that received the delayed or standard pruning timing treatments. Collectively, these studies emphasize that early spring sanitation measures are associated with reduced primary inoculum and are critically important for managing both downy mildew and powdery mildew. A savings of at least one fungicide application per year appears achievable when spring pruning is conducted thoroughly and slightly delayed compared with growers' current practices.

Predicting Damage to Hop Cones by Tetranychus urticae (Acari: Tetranychidae).

Twospotted spider mite (Tetranychus urticae Koch) is a cosmopolitan pest of numerous plants, including hop (Humulus lupulus L.). The most costly damage from the pest on hop results from infestation of cones, which are the harvested product, which can render crops unsalable if cones become discolored. We analyzed 14 yr of historical data from 312 individual experimental plots in western Oregon to identify risk factors associated with visual damage to hop cones from T. urticae. Logistic regression models were fit to estimate the probability of cone damage. The most predictive model was based on T. urticae-days during mid-July to harvest, which correctly predicted occurrence and nonoccurrence of cone damage in 91 and 93% of data sets, respectively, based on Youden's index. A second model based on the ratio of T. urticae to predatory arthropods late in the season correctly predicted cone damage in 92% of data sets and nonoccurrence of damage in 77% of data sets. The model based on T. urticae abundance performed similarly when validated in 23 commercial hop yards, whereas the model based on the predator:prey ratio was relatively conservative and yielded false-positive predictions in 11 of the 23 yards. Antecedents of these risk factors were explored and quantified by structural equation modeling. A simple path diagram was constructed that conceptualizes T. urticae invasion of hop cones as dependent on prior density of the pest on leaves in early spring and summer, which in turn influences the development of predatory arthropods that mediate late-season density of the pest. In summary, the biological insights and models developed here provide guidance to pest managers on the likelihood of visual cone damage from T. urticae that can inform late-season management based on both abundance of the pest and its important predators. This is critically important because a formal economic threshold for T. urticae on hop does not exist and current management efforts may be mistimed to influence the pest when crop damage is most probable. More broadly, this research suggests that current management practices that target T. urticae early in the season may in fact predispose yards to later outbreaks of the pest.

Development of partial ontogenic resistance to powdery mildew in hop cones and its management implications.

Knowledge of processes leading to crop damage is central to devising rational approaches to disease management. Multiple experiments established that infection of hop cones by Podosphaera macularis was most severe if inoculation occurred within 15 to 21 days after bloom. This period of infection was associated with the most pronounced reductions in alpha acids, cone color, and accelerated maturation of cones. Susceptibility of cones to powdery mildew decreased progressively after the transition from bloom to cone development, although complete immunity to the disease failed to develop. Maturation of cone tissues was associated with multiple significant affects on the pathogen manifested as reduced germination of conidia, diminished frequency of penetration of bracts, lengthening of the latent period, and decreased sporulation. Cones challenged with P. macularis in juvenile developmental stages also led to greater frequency of colonization by a complex of saprophytic, secondary fungi. Since no developmental stage of cones was immune to powdery mildew, the incidence of powdery mildew continued to increase over time and exceeded 86% by late summer. In field experiments with a moderately susceptible cultivar, the incidence of cones with powdery mildew was statistically similar when fungicide applications were made season-long or targeted only to the juvenile stages of cone development. These studies establish that partial ontogenic resistance develops in hop cones and may influence multiple phases of the infection process and pathogen reproduction. The results further reinforce the concept that the efficacy of a fungicide program may depend largely on timing of a small number of sprays during a relatively brief period of cone development. However in practice, targeting fungicide and other management tactics to periods of enhanced juvenile susceptibility may be complicated by a high degree of asynchrony in cone development and other factors that are situation-dependent.