Unified model of short- and long-term HIV viral rebound for clinical trial planning.

Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. Typically suspension of therapy is rapidly followed by rebound of viral loads to high, pre-therapy levels. Indeed, a recent study showed that approximately 90% of treatment interruption study participants show viral rebound within at most a few months of therapy suspension, but the remaining 10%, showed viral rebound some months, or years, after ART suspension. Some may even never rebound. We investigate and compare branching process models aimed at gaining insight into these viral dynamics. Specifically, we provide a theory that explains both short- and long-term viral rebounds, and post-treatment control, via a multitype branching process with time-inhomogeneous rates, validated with data from Li et al. (Li et al. 2016 AIDS30, 343-353. (doi:10.1097/QAD.0000000000000953)). We discuss the associated biological interpretation and implications of our best-fit model. To test the effectiveness of an experimental intervention in delaying or preventing rebound, the standard practice is to suspend therapy and monitor the study participants for rebound. We close with a discussion of an important application of our modelling in the design of such clinical trials.

Comparison of animal daily doses and days of therapy for antimicrobials in species of veterinary importance.

Characterizing antimicrobial use in animal populations is critical for purposes of antimicrobial stewardship. While dose-based metrics such as the animal daily dose (ADD) are typically used for such purposes, duration of therapy is emerging as a critical and more intuitive metric. In theory, the number of ADDs should approximate the number of days of therapy (DOTs), but no studies have examined whether this is the case. The objective of this study was to compare antimicrobial ADDs with antimicrobial DOTs in three populations: canine patients, large animal hospital patients, and dairy herds. In the first two populations, dose-based metrics were calculated using administrative hospital records while duration-based metrics were ascertained from manual chart review of individual animals. In the dairy herds, both metrics were obtained via farmer self-report. We found that the correlation between the number of ADDs and DOTs was poor for hospital patients (Lin correlation coefficients of 0.16 and 0.18 for small and large animals, respectively) and that there were often large differences between the two metrics for all populations, with ADDs most often overestimating the number of DOTs. While the median (IQR) differences between the number of DOTs and ADDs were relatively small (-9.4 (-25.7-(-0.92)), 0.34 (-5.0-4.0), and 0.0 (-18.0-9.0) among canine patients, large animal hospital patients, and dairy herds, respectively), the limits of agreement (-89.4-13.2, -37.7-9.9, and -100.0-53.0, respectively) were likely too large to be acceptable for most investigative purposes. Increased discrepancies between the two metrics were significantly associated with certain animal species (e.g., dogs, small ruminants) and drug classes (e.g., penicillins, cephalosporins, macrolides), decreased animal weight, and increased length of hospital stay. While the number of ADDs can approximate the number of DOTs under certain circumstances, the large limits of agreement between these two measurements suggest that the ADD is generally not a reliable proxy for the duration of therapy.

Pet Ownership Protects Against Recurrence of Clostridioides difficile Infection.

BACKGROUND: Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated and health care-associated diarrhea in humans. Recurrent CDI (R-CDI) occurs in ~20%-30% of patients with CDI and results in increased morbidity, mortality, and hospital costs. Genomic analyses have shown overlap of C. difficile isolates from animals and people, suggesting that a zoonotic reservoir may contribute to recurrence. The objective of this study was to determine whether pet ownership is a risk factor for recurrence of CDI. METHODS: We conducted a case-control study among patients with recurrent CDI (cases; n = 86) and patients with nonrecurrent CDI (controls; n = 146). Multivariable logistic regression modeling was used to determine the association between recurrence of CDI and pet ownership while accounting for patient-level risk factors. RESULTS: Pet ownership was not significantly associated with recurrence of CDI (odds ratio [OR], 1.02; 95% confidence interval [CI], 0.38-2.72; P = 0.965) among all patients (n = 232). However, among the subset of patients with community-associated or community-onset health care facility-acquired CDI (n = 127), increasing contact with pets was increasingly protective against recurrence: for every point increase in a pet contact score (out of 7 possible points), the odds of recurrence decreased by 14% (OR, 0.86; 95% CI, 0.74-1.00; P = 0.051). CONCLUSIONS: Close interactions with pets appear protective against the recurrence of community-acquired CDI. A potential mechanism may involve beneficial contributions to the microbiota of pet owners afflicted with CDI, as has been observed for other conditions such as atopy, obesity, and food allergies. However, more research is needed to understand the interactions between pets, owners, and their microbiota.