Mycobacteriophages are viruses that infect mycobacterial hosts such as Mycobacterium smegmatis and Mycobacterium tuberculosis. All mycobacteriophages characterized to date are dsDNA tailed phages, and have either siphoviral or myoviral morphotypes. However, their genetic diversity is considerable, and although sixty-two genomes have been sequenced and comparatively analyzed, these likely represent only a small portion of the diversity of the mycobacteriophage population at large. Here we report the isolation, sequencing and comparative genomic analysis of 18 new mycobacteriophages isolated from geographically distinct locations within the United States. Although no clear correlation between location and genome type can be discerned, these genomes expand our knowledge of mycobacteriophage diversity and enhance our understanding of the roles of mobile elements in viral evolution. Expansion of the number of mycobacteriophages grouped within Cluster A provides insights into the basis of immune specificity in these temperate phages, and we also describe a novel example of apparent immunity theft. The isolation and genomic analysis of bacteriophages by freshman college students provides an example of an authentic research experience for novice scientists.

BackgroundMen who have sex with men (MSM) frequently seek partners through mobile apps (geosocial networking [GSN] apps). However, it is unclear whether GSN apps’ use is associated with the increase in HIV incidence among MSM.ObjectiveThe aim of this study was to clarify the characteristics of GSN apps’ users and to determine the association and putative mechanisms between GSN apps’ use behavior and HIV incidence.MethodsWe conducted an 18-month prospective cohort study of MSM in Shenyang, China, and the participants were surveyed every 3 months from March 2015 to December 2016. An in-person interview collected information on sociodemographics, GSN apps’ use, recreational drug use, and sexual behaviors. In addition, blood was drawn to test for HIV and syphilis. We used a multivariable Cox regression model to determine possible predictors for increased HIV incidence.ResultsOf the enrolled 686 HIV-negative MSM, 431 (431/686, 62.8%) were GSN apps’ users. Compared with GSN apps’ nonusers, GSN apps’ users were younger; had an earlier age of sexual debut; and in the past 3 months, were more likely to have used recreational drugs, more likely to have had 5 or more casual partners (CPs), more likely to have had group sex with males, and more likely to have had condomless anal intercourse (CAI) with male steady partners (SPs). In addition, 59.4% (256/431) of the GSN apps’ users were willing to accept HIV and AIDS prevention information push services through GSN apps. In total, 19 MSM seroconverted to HIV during the follow-up period; the HIV incidence density rate was 8.5 (95% CI 5.0-13.5) per 100 person-years (PY) among GSN apps’ users and 2.0 (95% CI 0.4-5.8) per 100 PY among nonusers. New HIV infections were independently associated with ever using GSN apps to seek male sexual partners (P=.04) and in the past 3 months, using recreational drugs (P=.048), having group sex with males (P=.01), and having CAI with male CPs (P=.02).ConclusionsGSN apps’ use is associated with higher HIV incidence and may be mediated through recreational drug use and having multiple CPs. Researchers must develop an intervention propagated through GSN apps to reach this high-risk population to mitigate the HIV epidemic in the MSM community.

Background Pre-exposure prophylaxis (PrEP) is a promising and effective tool to prevent human immunodeficiency virus (HIV) transmission; however, context-specific data to guide optimal implementation are currently lacking in China. This study aims to systematically collect comprehensive, empirical data to determine effective ways to implement PrEP among at-risk men who have sex with men (MSM) in China. Methods The CROPrEP project, a real-world study of PrEP use, will recruit 1000 high-risk HIV-negative MSM participants from four cities in China, who will be able to choose between daily or event-driven dosing regimens, according to their preference. Participants will be followed up at months 1, 3, 6, 9, and 12 for PrEP provision, clinical evaluation, laboratory testing (e.g., emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) concentrations, and HIV/sexually transmitted infections), alongside detailed, self-administered online questionnaires regarding sexual behaviors, adherence, and attitudes. Online weekly notes will be used to record pill use and sexual practice. Various measurements will be triangulated to assess adherence, including: self-reported adherence, pill count, and drug concentration. A propensity score matching model will be fitted to examine the effectiveness of PrEP use in HIV seroconversion compared with non-PrEP users selected from a local expanding cohort study of HIV-1-negative MSM at participating research centers. Analyses using a generalized estimating equation model will focus on elucidation of the cascade of PrEP implementation, effectiveness, safety, and possible effects of PrEP use on sexual behaviors. This study will provide a comprehensive assessment of real-world PrEP use among Chinese MSM, to develop guidelines and strategies for PrEP implementation in China. Discussion The CROPrEP project is the first study of the TDF/FTC combination as PrEP in China, which will provide primary data on PrEP implementation, including: the cascade of PrEP use, “real-world” effectiveness, adherence, and safety. The findings from this study have potential to be vital for promoting the integration of PrEP within the portfolio of HIV prevention interventions and developing guidance on PrEP implementation in China. Trial registration ChiCTR-IIN-17013762 (Chinese Clinical Trial Registry). Date of registration: 8 December 2017.

Background: Assisted partner notification (PN) is an effective approach for increasing HIV testing among heterosexual partners. There is sparse evidence on its effect among sexual partners of men who have sex with men (MSM). Methods: A randomized controlled trial was conducted to compare the effect of assisted PN and passive PN interventions on uptake of HIV testing among male and female sexual partners of newly HIVdiagnosed MSM. In the passive PN group, participants were encouraged to disclose their HIV status and refer and persuade sexual partners to access HIV testing services (HTS). In the assisted PN group, participants were further provided with HIV self-testing kits for sexual partners to take a test at home or allow a community health worker from MSM-serving community-based organization (CBO) to anonymously refer and persuade their sexual partners to access HTS. The primary outcome was the proportion of index cases who had any sexual partner accessing HTS within four months after randomization. This trial is registered with chictr.org.cn, ChiCTR180 0 017813. Findings: Between August 2017 and January 2019, 187 MSM newly diagnosed with HIV in a large city Shenyang in northern China were enrolled in the study and randomly assigned to either passive PN (n = 90) or assisted PN (n = 97) study groups. The proportion of index cases who disclosed their HIV status to any sexual partners within three months of randomization was similar between passive PN (57%, 95% confidence interval [CI]: 46-67%) and assisted PN groups (58%, 95% CI: 4 8-6 8%). During four months of follow-up, the number of sexual partners named, referred to HTS, tested and testing positive per index case was 3 • 2, 0 • 7, 0 • 2 and 0 • 03 in the passive PN group, and 4 • 0, 1 • 0, 0 • 5 and 0 • 10 in the assisted PN group. Thirty-five percent of index cases in the assisted PN group had any sexual partners accessing HIV testing compared to 17% in the passive PN group (P = 0 • 004); 49% sexual partners who were disclosed by index cases in the assisted PN group had access HTS compared to 28% in the passive PN group (P = 0 • 007). Interpretation: The assisted PN strategy incorporating HIV self-testing and CBO outreach can increase uptake of HIV testing among sexual partners of MSM who were recently diagnosed with HIV.

Stochastic transmission dynamic models are needed to quantify the uncertainty in estimates and predictions during outbreaks of infectious diseases. We previously developed a calibration method for stochastic epidemic compartmental models, called Multiple Shooting for Stochastic Systems (MSS), and demonstrated its competitive performance against a number of existing state-of-the-art calibration methods. The existing MSS method, however, lacks a mechanism against filter degeneracy, a phenomenon that results in parameter posterior distributions that are weighted heavily around a single value. As such, when filter degeneracy occurs, the posterior distributions of parameter estimates will not yield reliable credible or prediction intervals for parameter estimates and predictions. In this work, we extend the MSS method by evaluating and incorporating two resampling techniques to detect and resolve filter degeneracy. Using simulation experiments, we demonstrate that an extended MSS method produces credible and prediction intervals with desired coverage in estimating key epidemic parameters (e.g. mean duration of infectiousness and R0) and short- and long-term predictions (e.g. one and three-week forecasts, timing and number of cases at the epidemic peak, and final epidemic size). Applying the extended MSS approach to a humidity-based stochastic compartmental influenza model, we were able to accurately predict influenza-like illness activity reported by U.S. Centers for Disease Control and Prevention from 10 regions as well as city-level influenza activity using real-time, city-specific Google search query data from 119 U.S. cities between 2003 and 2014.