Real-world use of long-acting cabotegravir and rilpivirine: 12-month results of the inJectable Antiretroviral therapy feasiBility Study (JABS).

OBJECTIVES: The inJectable Antiretroviral feasiBility Study (JABS) aimed to evaluate the implementation of long-acting regimens in a 'real world' Australian setting, with inclusion of participants with complex medical needs, social vulnerability and/or historical non-adherence. METHODS: JABS was a 12-month, single-centre, single-arm, open-label phase IV study of long-acting cabotegravir 600 mg plus rilpivirine 900 mg administered intramuscularly every 2 months to adults with treated HIV-1 infection. The primary endpoint was the proportion of attendances and administration of injections within a 14-day dosing window over 12 months, out of the total prescribed doses. Secondary endpoints included proportions of missed appointments, use of oral bridging, discontinuations, virological failures, adverse events and participant-reported outcomes. A multidisciplinary adherence programme embedded in the clinical service known as REACH provided support to JABS participants. RESULTS: Of 60 participants enrolled by May 2022, 60% had one or more complexity or vulnerability factors identified, including absence of social supports (50%), mental health issues, alcohol or drug use (30%) and financial hardship or instability (13%), among others. Twenty-seven per cent of participants had historical non-adherence to antiretroviral therapy. Out of 395 prescribed doses, 97.2% of injections were administered within correct dosing windows at clinic visits. Two courses of short-term oral bridging were required. The rate of injection site reactions was 29%, the majority being grade 1-2. There were no virological failures, no serious adverse events and only one injection-related study discontinuation. High baseline treatment satisfaction and acceptability of injections increased by month 12. Those with vulnerability factors had similar adherence to injections as those without such factors. Ninety-eight per cent of the participants who completed 12 months on the study have maintained long-acting therapy, virological suppression and retention in care. CONCLUSIONS: Long-acting cabotegravir plus rilpivirine was associated with very high adherence, maintenance of virological suppression, safety and treatment satisfaction in a diverse Australian clinic population, comparable to results of phase III randomized clinical trials. Individuals with vulnerability factors can achieve adherence to injections with individualized support. Long-acting therapies in this group can increase the subsequent engagement in clinical care.

Impact of continuous low-dose antibiotic prophylaxis on growth in children with vesicoureteral reflux.

BACKGROUND: Continuous antibiotic prophylaxis (CAP) is a mainstay of treatment for children with vesicoureteral reflux (VUR). There has been an increasing focus on the effect of antibiotics on gut microbiota and subsequent repercussions on growth. Continuous antibiotic prophylaxis is generally considered safe; however, its impact on growth in children with VUR remains unknown. OBJECTIVE: This objective of this study was to determine whether CAP altered height, weight, or body mass index (BMI) in children with VUR. STUDY DESIGN: Children diagnosed with primary VUR were identified. Demographics including weight and height percentiles, BMI and BMI percentiles, age, gender, antibiotic class, prior antibiotic use, urinary tract infection history, and breakthrough infections were tested in univariate and multivariate analyses. Primary outcome was change in BMI as well as weight, height, and BMI percentiles. RESULTS: One hundred eighty patients (146 girls, 34 boys) were prescribed CAP at mean age of 29.2 ± 26.2 months. Mean follow-up on CAP was 4.1 ± 3.3 years, with median follow-up of 3.08 years. Mean increase in weight percentile was 1.49 (2.02 males, 1.37 females; P = 0.46). Mean decrease in height percentile was -4.44 (-2.18 males, -4.95 females; P = 0.51). Age at diagnosis (P = 0.004) and history of prior treatment courses of antibiotics (P = 0.007) were associated with a significant BMI increase (Fig. 1). Body mass index percentile increased from 58.4 to 66.5; however, this increase was only significant in children aged above 1 year (P < 0.0001). Of note, children above 1 year of age were significantly more likely to have a history of prior treatment courses of antibiotics (58% vs 32%; P < 0.0001), and when controlling for prior antibiotic use, the increase in BMI percentile in those over 1 year of age did not reach significance. DISCUSSION: The use of antibiotics has been associated with alterations in pediatric growth parameters in both animal models and clinical studies. However, little information exists on the impact of prophylactic-dosed antibiotics on growth. While this study is limited by the retrospective analysis and small sample size, it was found that the use of CAP did impact growth parameters, with a stronger effect seen in children who had received prior treatment courses of antibiotics before the infection leading to the initiation of CAP. CONCLUSION: Continuous antibiotic prophylaxis was correlated with significant increase in BMI in children with prior antibiotic usage and a significant increase in BMI percentile in children aged above 1 year. Continuous antibiotic prophylaxis was also associated with decreased height percentiles, particularly in patients aged less than 1 year, though it did not reach statistical significance. Further analysis is needed to investigate whether these effects on weight, height, and BMI are persistent and clinically significant.

Effect of endoscopic white light on the developing rat retina.

OBJECTIVE: Our goal was determine the effect of endoscopic white light on the developing mammalian retina by quantitative histological analysis. STUDY DESIGN: Albino rats at postnatal days 10 (n = 16) and 16 (n = 20) were exposed to endoscopic white light for 1 h, while an equal number of littermate controls were not exposed, but otherwise treated identically. The thickness of the outer nuclear layer (ONL) and the total retinal thickness were measured light microscopically using a computer-assisted morphometry program. RESULTS: We found no statistically significant decrease in the thickness of the ONL or the total retinal thickness, nor were any significant decreases found in the ONL or the total retinal thickness for male or female groups. CONCLUSION: Endoscopic white light does not cause damage to the developing rodent neural retina detectable at the light microscopic level.

The structure of the aflatoxin B1-DNA adduct at N7 of guanine. Theoretical intercalation and covalent adduct models.

Two theoretical models are proposed for the conformational structure of both intercalated and covalent adduct complexes of aflatoxin B1, designated AFB1, with N7 of guanine of DNA. The covalent adduct model requires the DNA to kink a minimum of 39 degrees about the covalent site of the C8 and N7 atoms comprising the bond of the covalent complex. The preference of AFB1 for specific G bases within a sequence of GC content followed that of experimental studies with the added feature that for binding to the third G base of a tetramer sequence from the 3'-end, the AFB1 displayed enhanced binding at the 3' site of the targeted guanosine. Binding of AFB1 to the second G base of a tetramer sequence from the 3'-end leads to preference for a 5' site of the targeted guanosine. Inhibition of AFB1's interaction with the targeted DNA in the presence of intercalated ethidium bromide is explained by these proposed models.