Facilitating Next-Generation Pre-Exposure Prophylaxis Clinical Trials Using HIV Recent Infection Assays: A Consensus Statement from the Forum HIV Prevention Trial Design Project

Standard-of-care HIV pre-exposure prophylaxis (PrEP) is highly efficacious, but uptake of and persistence on a daily oral pill is low in many settings. Evaluation of alternate PrEP products will require innovation to avoid the unpractically large sample sizes in noninferiority trials. We propose estimating HIV incidence in people not on PrEP as an external counterfactual to which on-PrEP incidence in trial subjects can be compared. HIV recent infection testing algorithms (RITAs), such as the limiting antigen avidity assay plus viral load used on specimens from untreated HIV positive people identified during screening, is one possible approach. Its feasibility is partly dependent on the sample size needed to ensure adequate power, which is impacted by RITA performance, the number of recent infections identified, the expected efficacy of the intervention, and other factors. Screening sample sizes to support detection of an 80% reduction in incidence for 3 key populations are more modest, and comparable to the number of participants in recent phase III PrEP trials. Sample sizes would be significantly larger in populations with lower incidence, where the false recency rate is higher or if PrEP efficacy is expected to be lower. Our proposed counterfactual approach appears to be feasible, offers high statistical power, and is nearly contemporaneous with the on-PrEP population. It will be important to monitor the performance of this approach during new product development for HIV prevention. If successful, it could be a model for preventive HIV vaccines and prevention of other infectious diseases

The associations between serum adiponectin, leptin, C-reactive protein, insulin, and serum long-chain omega-3 fatty acids in Labrador Retrievers

Renee M Streeter,1 Angela M Struble,1 Sabine Mann,2 Daryl V Nydam,2 John E Bauer,3 Marta G Castelhano,1 Rory J Todhunter,1 Bethany P Cummings,4 Joseph J Wakshlag11Department of Clinical Sciences, 2Department of Population Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA; 3Department of Clinical Sciences, Texas A&M University, College Station, TX, USA; 4Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, USAAbstract: Obesity has been associated with an increased inflammatory response and insulin resistance due to adipose tissue–derived adipokines and increases in C-reactive protein (CRP). Dogs appear to be similar to other species with the exception of adiponectin, which might not be affected by obesity status. Serum long-chain polyunsaturated fatty acid concentrations have been positively and negatively associated with serum adipokines. The aim of the study was to examine the relationship between leptin, CRP, adiponectin, and insulin to body condition score (BCS) and to the long-chain omega-3 fatty acids in serum lipoproteins, including alpha-linolenic acid, eicosapentaenoic acid (EPA), docosapentanenoic acid (DPA), and docosahexaenoic acid (DHA) as a reflection of dietary omega-3 status in the Labrador Retriever. Seventy-seven Labrador Retrievers were evaluated for BCS, percent fasting serum lipoprotein fatty acid concentrations, as well as serum leptin, adiponectin, insulin, and CRP. A multivariable general linear regression model was constructed to examine the association between the dependent variables leptin, CRP, adiponectin, and insulin and the predictor variables of BCS, age, and sex, as well as concentrations of alpha-linolenic acid, EPA, DHA, and DPA. Adiponectin concentration was positively associated with age (P<0.0008), EPA (P=0.027) and negatively associated with DHA (P=0.008). Leptin concentration was positively associated with an increased DHA (P=0.009), BCS (P<0.0001), age (P=0.02), and decreased DPA (P=0.06). Insulin concentration was only associated with BCS (P<0.0001), and no meaningful associations were found for CRP. Longer chain omega-3 fatty acids may play a role in regulating adiponectin concentrations in dogs. However, because insulin concentrations were associated only with BCSs, further examination of the role of adiponectin in canine obesity is warranted. EPA and DPA may reduce the overall inflammatory state in dogs as these omega-3 fatty acids reflect increased adiponectin (increased EPA and decreased DHA) and decreased leptin (decreased DHA and increased DPA).Keywords: dog, obesity, adiponectin, omega-3 fatty acid, insulin, lepti