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The prevention of HIV and unintended pregnancies is a public health priority. Multi-purpose prevention technologies capable of long-acting HIV and pregnancy prevention are desirable for women. Here, we utilized a preclinical macaque model to evaluate the pharmacokinetics of biodegradable ε-polycaprolactone implants delivering the antiretroviral islatravir (ISL) and the contraceptive etonogestrel (ENG). Three implants were tested: ISL-62 mg, ISL-98 mg, and ENG-33 mg. Animals received one or two ISL-eluting implants, with doses of 42, 66, or 108 µg of ISL/day with or without an additional ENG-33 mg implant (31 µg/day). Drug release increased linearly with dose with median [range] plasma ISL levels of 1.3 [1.0-2.5], 1.9 [1.2-6.3] and 2.8 [2.3-11.6], respectively. The ISL-62 and 98 mg implants demonstrated stable drug release over three months with ISL-triphosphate (ISL-TP) concentr54ations in PBMCs above levels predicted to be efficacious for PrEP. Similarly, ENG implants demonstrated sustained drug release with median [range] plasma ENG levels of 495 [229-1110] pg/mL, which suppressed progesterone within two weeks and showed no evidence of altering ISL pharmacokinetics. Two of the six ISL-98 mg implants broke during the study and induced implant-site reactions, whereas no reactions were observed with intact implants. We show that ISL and ENG biodegradable implants are safe and yield sufficient drug levels to achieve prevention targets. The evaluation of optimized implants with increased mechanical robustness is underway for improved durability and vaginal efficacy in a SHIV challenge model.

Ultra-long-acting delivery platforms for HIV pre-exposure prophylaxis (PrEP) may increase adherence and maximize public health benefit. We report on an injectable, biodegradable, and removable in-situ forming implant (ISFI) that is administered subcutaneously and can release the integrase inhibitor cabotegravir (CAB) above protective benchmarks for more than 6 months. CAB ISFIs are well-tolerated in female mice and female macaques showing no signs of toxicity or chronic inflammation. In macaques, median plasma CAB concentrations exceed established PrEP protection benchmarks within 3 weeks and confer complete protection against repeated rectal SHIV challenges. Implant removal via a small incision in 2 macaques at week 12 results in a 7- to 48-fold decrease in plasma CAB levels within 72 hours. Modeling to translate CAB ISFI dosing suggests that a 3 mL injection would exceed protective benchmarks in humans for over 5 months post administration. Our results support the clinical advancement of CAB ISFIs for ultra-long-acting PrEP in humans., (© 2023. The Author(s).)

Approximately 67% of U.S. households have pets. Limited data are available on SARS-CoV-2 in pets. We assessed SARS-CoV-2 infection in pets during a COVID-19 household transmission investigation. Pets from households with ≥1 person with laboratory-confirmed COVID-19 were eligible for inclusion from April-May 2020. We enrolled 37 dogs and 19 cats from 34 households. All oropharyngeal, nasal, and rectal swabs tested negative by rRT-PCR; one dog's fur swabs (2%) tested positive by rRT-PCR at the first sampling. Among 47 pets with serological results, eight (17%) pets (four dogs, four cats) from 6/30 (20%) households had detectable SARS-CoV-2 neutralizing antibodies. In households with a seropositive pet, the proportion of people with laboratory-confirmed COVID-19 was greater (median 79%; range: 40-100%) compared to households with no seropositive pet (median 37%; range: 13-100%) ( p = 0.01). Thirty-three pets with serologic results had frequent daily contact (≥1 h) with the index patient before the person's COVID-19 diagnosis. Of these 33 pets, 14 (42%) had decreased contact with the index patient after diagnosis and none were seropositive; of the 19 (58%) pets with continued contact, four (21%) were seropositive. Seropositive pets likely acquired infection after contact with people with COVID-19. People with COVID-19 should restrict contact with pets and other animals.

Objective: To evaluate and compare outcome in dogs that underwent single-incision laparoscopic-assisted intestinal surgery (SILAIS) and open laparotomy (OL) for simple foreign body removal., Study Design: Retrospective study., Animals: Twenty-eight client-owned dogs that underwent SILAIS (n = 13) or OL (n = 15)., Methods: Foreign body removal via SILAIS was performed with a commercially available single-port device. After laparoscopic evaluation, a wound retraction device (WRD) was inserted. The small intestine was extracorporeally explored, and foreign body removal was performed. The surgeon's hand was inserted through the WRD to palpate portions of the gastrointestinal tract not able to be extracorporeally evaluated. Open laparotomy with foreign body removal was performed via a ventral midline approach. Medical records were retrospectively reviewed, and perioperative data were collected. Follow-up data were collected with a standardized questionnaire with the referring veterinarian and/or owner via telephone interview., Results: No postoperative complications were encountered in either the SILAIS or the OL group, and all dogs were successfully discharged from the hospital. Conversion from SILAIS to OL occurred in 3/13 cases. There was no significant difference in duration of hospitalization, duration of time to recovery, or surgical time between surgical approaches (SILAIS vs OL)., Conclusion: Single-incision laparoscopic-assisted intestinal surgery for foreign body removal was not significantly different from OL in a variety of outcome measures in this cohort of dogs. Diagnostic imaging including ultrasonography or computed tomography may improve appropriate case selection for SILAIS for simple foreign body removal., Clinical Significance: Single-incision laparoscopic-assisted intestinal surgery offers a minimally invasive technique for simple small intestinal foreign body removal. Additional study is required to compare SILAIS with OL., (© 2018 The American College of Veterinary Surgeons.)

Objectives: To determine the influence of age, year of graduation, and video game experience on baseline laparoscopic psychomotor skills., Study Design: Cross-sectional., Sample Population: Licensed veterinarians (n = 38) and registered veterinary technicians (VTs) (n = 49)., Methods: A laparoscopic box trainer was set up at the 2016 Ontario Veterinary Medical Association (OVMA) and the 2016 Ontario Association of Veterinary Technicians (OAVT) conferences held in Toronto, Ontario, Canada. Participants volunteered to perform a single repetition of a peg transfer (PT) exercise. Participants were given a short demonstration of the PT task prior to testing. A Spearman's rank correlation (r s ) was used to identify associations between baseline psychomotor skills and self-reported surgical and non-surgical experiences collected via survey. Mann-Whitney U tests were used to compare PT scores in veterinarians and VTs. A P-value of < .05 was considered significant., Results: The mean age of participants was 36 years (range 21-67) and the majority were female (83%). In veterinarians, PT scores were highest in the most recent graduates (P = .01, r s  = 0.42), and PT scores increased with self-reported VG experience (P = .02, r s  = 0.38). PT scores correlated inversely with age (P = .02, r s  = -0.37). No associations were observed in VTs (P > .05). Veterinary technicians that frequently used chopsticks scored higher than those without chopstick experience (P = .04)., Conclusions: Age and year of graduation correlated inversely, while self-reported VG experience correlated positively with laparoscopic psychomotor skills of veterinarians, when assessed on a simulator. The use of chopsticks may contribute to the acquisition of psychomotor skills in VTs., (© 2017 The American College of Veterinary Surgeons.)