Best practice recommendations for the management of anxiety during the pegvaliase journey.

BACKGROUND: Pegvaliase, an enzyme substitution therapy, is a treatment option for phenylketonuria (PKU). Due to the neuropathophysiology and disease burden of PKU, individuals can experience baseline anxiety unrelated to pegvaliase therapy. In addition, there are aspects of pegvaliase therapy that may be anxiety-inducing for those considering or receiving treatment. The aim of this manuscript is to present best practice recommendations for the identification and management of anxiety symptoms that can occur along the pegvaliase journey. METHODS: A modified Delphi approach was used to seek consensus among a multidisciplinary panel of experts. To this end, an in-person meeting was held that was preceded by a medical specialist- and patient-specific survey to develop preliminary recommendations on ways to address anxiety along the pegvaliase journey. After the meeting, an additional survey was conducted to rank the proposed solutions and mitigation strategies from which a set of recommendations was developed. All recommendations were voted on with the aim of consensus generation, defined as achieving ≥75% agreement among experts. RESULTS: The panel reached consensus on a total of 28 best practice recommendations for the management of anxiety during the pre-treatment, induction and titration, early maintenance (pre-efficacy), and late maintenance (post-efficacy) stages. The recommendations offer strategies to identify and address the most common causes of pegvaliase-related anxiety, including self-injection, side effects, the titration schedule, prescribed dietary changes, and variable time to efficacy. Overall, managing anxiety in those considering or receiving pegvaliase involves patient-centered communication, shared decision-making, and personalized treatment plans. CONCLUSIONS: The best practice recommendations described herein can guide healthcare providers in proactively addressing anxiety during the different stages of pegvaliase treatment, and support providers with initiating and managing pegvaliase in individuals who may experience baseline and treatment-related anxiety.

Murine GFP-Mx1 forms nuclear condensates and associates with cytoplasmic intermediate filaments: Novel antiviral activity against VSV.

Type I and III interferons induce expression of the "myxovirus resistance proteins" MxA in human cells and its ortholog Mx1 in murine cells. Human MxA forms cytoplasmic structures, whereas murine Mx1 forms nuclear bodies. Whereas both HuMxA and MuMx1 are antiviral toward influenza A virus (FLUAV) (an orthomyxovirus), only HuMxA is considered antiviral toward vesicular stomatitis virus (VSV) (a rhabdovirus). We previously reported that the cytoplasmic human GFP-MxA structures were phase-separated membraneless organelles ("biomolecular condensates"). In the present study, we investigated whether nuclear murine Mx1 structures might also represent phase-separated biomolecular condensates. The transient expression of murine GFP-Mx1 in human Huh7 hepatoma, human Mich-2H6 melanoma, and murine NIH 3T3 cells led to the appearance of Mx1 nuclear bodies. These GFP-MuMx1 nuclear bodies were rapidly disassembled by exposing cells to 1,6-hexanediol (5%, w/v), or to hypotonic buffer (40-50 mosm), consistent with properties of membraneless phase-separated condensates. Fluorescence recovery after photobleaching (FRAP) assays revealed that the GFP-MuMx1 nuclear bodies upon photobleaching showed a slow partial recovery (mobile fraction: ∼18%) suggestive of a gel-like consistency. Surprisingly, expression of GFP-MuMx1 in Huh7 cells also led to the appearance of GFP-MuMx1 in 20-30% of transfected cells in a novel cytoplasmic giantin-based intermediate filament meshwork and in cytoplasmic bodies. Remarkably, Huh7 cells with cytoplasmic murine GFP-MuMx1 filaments, but not those with only nuclear bodies, showed antiviral activity toward VSV. Thus, GFP-MuMx1 nuclear bodies comprised phase-separated condensates. Unexpectedly, GFP-MuMx1 in Huh7 cells also associated with cytoplasmic giantin-based intermediate filaments, and such cells showed antiviral activity toward VSV.

Same-Day HIV Pre-Exposure Prophylaxis (PrEP) Initiation During Drop-in Sexually Transmitted Diseases Clinic Appointments Is a Highly Acceptable, Feasible, and Safe Model that Engages Individuals at Risk for HIV into PrEP Care.

OBJECTIVE: Strategies to increase pre-exposure prophylaxis (PrEP) uptake are needed. We hypothesized that same-day PrEP initiation in a sexually transmitted diseases (STD) clinic would be acceptable, feasible, and safe, and that individuals would engage in ongoing PrEP care. METHOD: Individuals aged ≥ 18 years were evaluated for PrEP. Exclusion criteria were HIV, history of renal dysfunction or chronic hepatitis B infection, pregnancy, indications for HIV post-exposure prophylaxis, or positive screen for acute HIV symptoms. One hundred individuals received a free 30-day PrEP starter pack and met with a patient navigator to establish ongoing care. Bivariate analysis and multivariable logistic regression were used to compare individuals who did and did not attend at least 1 PrEP follow-up appointment within 180 days of enrollment. Client satisfaction surveys were given 3 months after enrollment. RESULTS: The majority (78%) of participants completed at least 1 PrEP follow-up appointment, and 57% attended at least 2 follow-up appointments. After adjusting for race and ethnicity, age, health insurance status, and annual income, only income was associated with follow-up appointment attendance. Each additional $10,000 increase in income was associated with a 1.7-fold increase in the odds of attending a PrEP follow-up appointment (95% confidence interval, 1.07-2.66, P = .02). The majority (54%) of individuals completed the satisfaction survey and all respondents liked the option of same-day PrEP initiation. CONCLUSIONS: Our study suggests STD clinic-based, same-day PrEP initiation is acceptable, feasible, safe, and links a high proportion of individuals into ongoing PrEP care. Additional resources may be needed to support low-income individuals' retention in care.

Acute Trigeminal Neuralgia Associated with Initiation of Emtricitabine/Tenofovir for HIV Pre-Exposure Prophylaxis.

HIV pre-exposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) fixed-dose combination (FTC/TDF) is undergoing rapid scale-up in the United States. While FTC/TDF is typically well tolerated, to our knowledge, cranial nerve pathology associated with FTC/TDF has not been previously described. We report the case of a 35-year-old patient who began FTC/TDF PrEP and developed acute trigeminal neuralgia. The neurologic symptoms resolved after treatment discontinuation and recurred upon rechallenge, resulting in permanent discontinuation of PrEP treatment.

Sexually Transmitted Disease Testing of Human Immunodeficiency Virus-Infected Men Who Have Sex With Men: Room for Improvement.

BACKGROUND: In the United States, sexually transmitted infection (STI) testing is recommended at least annually for sexually active men who have sex with men (MSM). We evaluated human immunodeficiency virus (HIV) providers' STI testing practices and frequency of positive test results. METHODS: We analyzed data from HIV Outpatient Study (HOPS) participants who, from 2007 to 2014, completed a confidential survey about risk behaviors. Using medical records data, we assessed the frequency of gonorrhea, chlamydia, and syphilis testing and positive results during the year after the survey for MSM who reported sex without a condom in the prior 6 months. We compared testing frequency and positivity for men having 1, 2 to 3, and 4 or more sexual partners. Correlates of STI testing were assessed using general linear model to derive relative risks (RR) with associated 95% confidence intervals (CI). RESULTS: Among 719 MSM, testing frequency was 74.5%, 74.3%, and 82.9% for gonorrhea, chlamydia, and syphilis, respectively, and was higher in those men who reported more sexual partners (P < 0.001 for all). In multivariable analysis, testing for gonorrhea was significantly more likely among non-Hispanic black versus white men (RR, 1.17; 95% CI, 1.03-1.33), among men seen in private versus public clinics (RR, 1.16; 95% CI, 1.05-1.28), and among men with 2 to 3 and 4 or more sexual partners versus 1 partner (RR, 1.12; 95% CI, 1.02-1.23, and RR, 1.18; 95% CI, 1.08-1.30, respectively). Correlates of chlamydia and syphilis testing were similar. Test positivity was higher among men with more sexual partners: for gonorrhea 0.0%, 3.0%, and 6.7% for men with 1, 2 to 3, and 4 or more partners, respectively (P < 0.001, syphilis 3.7%, 3.8% and 12.5%, P < 0.001). CONCLUSIONS: Among HIV-infected MSM patients in HIV care who reported sex without a condom, subsequent testing was not documented in clinic records during the following year for up to a quarter of patients. Exploring why STI testing did not occur may improve patient care.

HIV Viral Load Monitoring Frequency and Risk of Treatment Failure among Immunologically Stable HIV-Infected Patients Prescribed Combination Antiretroviral Therapy.

The authors sought to assess whether viral load (VL) monitoring frequency was associated with differential rates of virologic failure (VF) among HIV Outpatient Study (HOPS) participants seen during 1999 to 2013, who had maintained VL <50 copies/mL, CD4 counts ≥300 cells/mm(3), and been prescribed a stable combination antiretroviral regimen for at least 2 years. The authors required VL and CD4 testing to have occurred regularly for the entire 2-year period. The authors assessed rates of VF comparing patients who maintained a frequent VL testing (≥3 VLs) to those who shifted to a less frequent schedule (2 VL) after the 2-year period. Virologic failure was observed among 116 of 573 participants. The authors did not detect statistically significant difference in frequency of VF among patients undergoing frequent (21.0%) versus less frequent VL testing (19.6%), even after multivariable adjustment. Biannual VL monitoring for stable patients with aviremia could generate substantial cost savings without the increased risk of VF.