Background Acute human immunodeficiency virus type 1 (HIV-1) infection is a major contributor to transmission of HIV-1. An understanding of acute HIV-1 infection may be important in the development of treatment strategies to eradicate HIV-1 or achieve a functional cure. Methods We performed twice-weekly qualitative plasma HIV-1 RNA nucleic acid testing in 2276 volunteers who were at high risk for HIV-1 infection. For participants in whom acute HIV-1 infection was detected, clinical observations, quantitative measurements of plasma HIV-1 RNA levels (to assess viremia) and HIV antibodies, and results of immunophenotyping of lymphocytes were obtained twice weekly. Results Fifty of 112 volunteers with acute HIV-1 infection had two or more blood samples collected before HIV-1 antibodies were detected. The median peak viremia (6.7 log10 copies per milliliter) occurred 13 days after the first sample showed reactivity on nucleic acid testing. Reactivity on an enzyme immunoassay occurred at a median of 14 days. The nadir of viremia (4.3 log10 copies per milliliter) occurred at a median of 31 days and was nearly equivalent to the viral-load set point, the steady-state viremia that persists durably after resolution of acute viremia (median plasma HIV-1 RNA level, 4.4 log10 copies per milliliter). The peak viremia and downslope were correlated with the viral-load set point. Clinical manifestations of acute HIV-1 infection were most common just before and at the time of peak viremia. A median of one symptom of acute HIV-1 infection was recorded at a median of two study visits, and a median of one sign of acute HIV-1 infection was recorded at a median of three visits. Conclusions The viral-load set point occurred at a median of 31 days after the first detection of plasma viremia and correlated with peak viremia. Few symptoms and signs were observed during acute HIV-1 infection, and they were most common before peak viremia. (Funded by the Department of Defense and the National Institute of Allergy and Infectious Diseases.)

Background Gut microbiota may play a role in the natural history of cow’s milk allergy Objective To examine the association between early life gut microbiota and the resolution of cow’s milk allergy Methods We studied 226 children with milk allergy who were enrolled at infancy in the Consortium of Food Allergy (CoFAR) observational study of food allergy. Fecal samples were collected at age 3–16 months, and the children were followed longitudinally with clinical evaluation, milk-specific IgE levels, and milk skin prick test performed at enrollment, 6 months, 12 months, and yearly thereafter up until age 8 years. Gut microbiome was profiled by 16s rRNA sequencing and microbiome analyses performed using QIIME (Quantitative Insights into Microbial Ecology), PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States), and STAMP (Statistical Analysis of Metagenomic Profiles). Results Milk allergy resolved by age 8 years in 128 (56.6%) of the 226 children. Gut microbiome composition at age 3–6 months was associated with milk allergy resolution by age 8 years (PERMANOVA P = 0.047), with enrichment of Clostridia and Firmicutes in the infant gut microbiome of subjects whose milk allergy resolved. Metagenome functional prediction supported decreased fatty acid metabolism in the gut microbiome of subjects whose milk allergy resolved (η2 = 0.43, ANOVA P = 0.034). Conclusions Early infancy is a window during which gut microbiota may shape food allergy outcomes in childhood. Bacterial taxa within Clostridia and Firmicutes could be studied as probiotic candidates for milk allergy therapy.

Background Although studies of oral immunotherapy (OIT) for food allergy have shown promise, treatment is frequently complicated by adverse reactions and, even when successful, has limited long-term efficacy as benefits usually diminish when treatment is discontinued. Objective We sought to examine whether the addition of omalizumab to milk OIT (MOIT) reduces treatment-related reactions and/or improves outcomes. Methods This was a double-blind placebo-controlled trial with subjects randomized to omalizumab or placebo. Open-label MOIT was initiated after 4 months of omalizumab/placebo with escalation to maintenance over 22–40 weeks, followed by daily maintenance dosing through month-28. At month-28, omalizumab was discontinued and subjects passing an oral food challenge (OFC) continued OIT for 8 weeks, after which OIT was discontinued with re-challenge at month-32 to assess sustained unresponsiveness (SU). Results Fifty-seven subjects (7–32 years) were randomized, with no significant baseline differences in age, milk-specific IgE, skin tests, or OFCs. At month-28, 24 (88.9%) omalizumab-treated subjects and 20 (71.4%) placebo-treated subjects passed the 10 gram “desensitization” OFC (p=0.18). At month-32, SU was demonstrated in 48.1% in the omalizumab group and 35.7% in the placebo group (p=0.42). Adverse reactions were markedly reduced during OIT escalation in omalizumab subjects for percent doses/subject provoking symptoms (2.1% versus 16.1%; p=0.0005), dose-related reactions requiring treatment (0.0% versus 3.8%, p=0.0008), and doses required to achieve maintenance (198 versus 225; p=0.008). Conclusions In this first randomized double-blinded placebo-controlled trial of omalizumab in combination with food OIT, we found significant improvements in measurements of safety, but not in outcomes of efficacy (desensitization and SU). Trial Registration OIT and XolairR (Omalizumab) in Cow’s Milk Allergy, NCT01157117, http://clinicaltrials.gov/show/NCT01157117

BackgroundHistory and severity of atopic dermatitis (AD) are risk factors for peanut allergy. Recent evidence suggests that children can become sensitized to food allergens through an impaired skin barrier. Household peanut consumption, which correlates strongly with peanut protein levels in household dust, is a risk factor for peanut allergy.ObjectiveWe sought to assess whether environmental peanut exposure (EPE) is a risk for peanut sensitization and allergy and whether markers of an impaired skin barrier modify this risk.MethodsPeanut protein in household dust (in micrograms per gram) was assessed in highly atopic children (age, 3-15 months) recruited to the Consortium of Food Allergy Research Observational Study. History and severity of AD, peanut sensitization, and likely allergy (peanut-specific IgE, ≥5 kUA/mL) were assessed at recruitment into the Consortium of Food Allergy Research study.ResultsThere was an exposure-response relationship between peanut protein levels in household dust and peanut skin prick test (SPT) sensitization and likely allergy. In the final multivariate model an increase in 4 log2 EPE units increased the odds of peanut SPT sensitization (1.71-fold; 95% CI, 1.13- to 2.59-fold; P = .01) and likely peanut allergy (PA; 2.10-fold; 95% CI, 1.20- to 3.67-fold; P < .01). The effect of EPE on peanut SPT sensitization was augmented in children with a history of AD (OR, 1.97; 95% CI, 1.26-3.09; P < .01) and augmented even further in children with a history of severe AD (OR, 2.41; 95% CI, 1.30-4.47; P < .01); the effect of EPE on PA was also augmented in children with a history of AD (OR, 2.34; 95% CI, 1.31-4.18; P < .01).ConclusionExposure to peanut antigen in dust through an impaired skin barrier in atopically inflamed skin is a plausible route for peanut SPT sensitization and PA.

Peanut EPIT administration was safe and associated with a modest treatment response after 52 weeks, with the highest responses among younger children. This, when coupled with a high adherence and retention rate and significant changes in immune pathways, supports further investigation of this novel therapy.

Background There are few studies on the natural history of egg allergy and most are single site, not longitudinal, and have not identified early predictors of outcomes. Objective To describe the natural course of egg allergy and to identify early prognostic markers. Methods Children aged 3–15 months were enrolled in a multicenter observational study with either a convincing history of an immediate allergic reaction to egg and/or milk with a positive prick skin test (SPT) to the trigger food; and/or moderate-severe atopic dermatitis and a positive SPT to egg or milk. Children enrolled with a clinical history of egg allergy were followed longitudinally and resolution was established by successful ingestion. Results The egg-allergic cohort consists of 213 children followed to a median age of 74 months. Egg allergy resolved in 105 (49.3%), at a median age of 72 months. Factors that were most predictive of resolution included the following: initial reaction characteristics (isolated urticaria/angioedema vs other presentations), baseline egg-specific IgE level, egg SPT wheal size, atopic dermatitis severity, IgG4 and IL-4 response (all P<0.05). Numerous additional baseline clinical and demographic factors and laboratory assessments were not associated with resolution. Multivariate analysis identified baseline egg-specific IgE and initial reaction characteristics as strongly associated with resolution; a calculator to estimate resolution probabilities using these variables was established. Conclusions In this cohort of infants with egg allergy, about one half had resolved over 74 months of follow-up. Baseline egg-specific IgE and initial reaction characteristics were important predictors of the likelihood of resolution.

I INTRODUCTIONThis paper examines the influence of television on attendance at English FA Premier League football matches in the 1993-1994 season. It finds that satellite television has a significant net negative effect on such attendances.' This has potential consequences for the growing number of professional sports that are now broadcast live by satellite and/or cable television companies.'There have been numerous studies of sports attendance by economists. One of the major, but largely neglected, issues is the influence of television on the demand for tickets, which has potential significance for attendances together with the finances of individual clubs. In a system where earnings from television alone have increased by 3,0000/0 over the brief history of live coverage in the UK, there 'This is not to suggest, however, that the overall financial outcome is detrimental to football. The deal between the English Football Association and BSkyB is worth €214 million over the period 1992-1997. This is approximately six times the magnitude of the previous arrangement with terrestrial television. The payments system is analogous to a multipart tariff with each club receiving a fixed fee together with a sliding scale dependent on final position.'Satellite television began in the UK at the end of the 198Os, initially offering three channels dedicated to sport. Deregulation raised concerns that satellite companies would outbid terrestrial stations for major sporting events (Whannel, 1992).

Departments of the Army and Defense and National Institute of Allergy and Infectious Diseases.