Improving preparedness for introducing and scaling up long-acting HIV pre-exposure prophylaxis in Asia.

Long-acting injectable PrEP, particularly cabotegravir (CAB-LA), has the potential to enhance HIV prevention in Asia, and was the topic of a roundtable held in Singapore in June 2023. Despite proven efficacy, CAB-LA's impact in Asia is hindered by regulatory, manufacturing, and cost barriers. There is an urgent need to address these challenges to expedite CAB-LA's introduction and scale-up, including collaborative research, streamlined regulatory processes, and increased manufacturing capacity. We call for better preparedness in long-acting PrEP in research and implementation science, product licensing and accessibility, and capacity readiness for scale-up, to meet the significant demand among key populations in Asia.

Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

Safety and adherence of bictegravir/emtricitabine/tenofovir alafenamide for HIV post-exposure prophylaxis among adults in Guiyang China: a prospective cohort study.

BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).

Impact of switching to injectables cabotegravir and rilpivirine on sleep disturbances in a cohort of people living with HIV.

BACKGROUND: Recently, injectable cabotegravir/rilpivirine (ICAB/RPV) became available for HIV treatment. However, there are no real-life data on the impact of switching to ICAB/RPV on sleep disturbances (SD). Therefore, we aimed at assessing and investigating this aspect in our cohort. METHODS: A SD multidimensional assessment (Epworth Sleepiness scale, Insomnia severity Index, Berlin Questionnaire, and Pittsburg Sleep Quality Index, PSQI) was performed to all people who consented before starting ICAB/RPV and 12 wk after the switch. Demographics, life-style habits, laboratory, and clinical data were collected from medical health records. RESULTS: To June 2023, 46 people were included, 76.1% males, with a median age of 48.5 (IQR: 41-57), 50% had multimorbidity, 13% was on polypharmacy. Median age with HIV and CD4 + T cell count nadir were 10 (5-19.5) years and 360 (205-500) cell/mm3, respectively. The reason to start a long-acting strategy was person's choice in all cases. Baseline antiretroviral regimens were mostly: tenofovir alafenamide/emtricitabine/rilpivirine (39.1%) and dolutegravir/lamivudine (32.6%). No significant changes were observed in any of the scores for each questionnaire, but for a worsening PSQI. 37% people reported a subjectively improved sleep quality, even if statistically significant changes were not observed in almost all the sleep parameters. CONCLUSIONS: To the best of our knowledge, this is the first study exploring impact of switching to ICAB/RPV on SD. Despite integrase inhibitor have been associated with SD, we did not observed a negative impact on sleep quality after the switch to ICAB/RPV. More studies and with larger number of people are necessary to confirm our results.

Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

Safety analysis of Oseltamivir and Baloxavir Marboxil after market approval: a pharmacovigilance study based on the FDA adverse event reporting system.

BACKGROUND AND OBJECTIVES: Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references. METHODS: A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug. RESULTS: Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26]. CONCLUSION: Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.

Lamivudine plus dolutegravir as a switch strategy in children: three case reports.

Lamivudine (3TC)/dolutegravir (DTG) single tablet regimen (STR) has shown long-term efficacy and tolerability in people living with HIV (PLWH). Dolutegravir has been approved for use in children, while data on the efficacy of 3TC plus DTG in maintaining virological suppression in this population are still under evaluation. In this case series, we describe three children with perinatally acquired HIV who maintained virological suppression after switching antiretroviral therapy to DTG/3TC. We present three case reports of three children enrolled in the Italian Register for HIV Infection in Children: a 9-year-old boy, a 10-year-old girl, and a 2-year-old girl with perinatally acquired HIV who immediately started antiretroviral therapy with a three-drug regimen upon diagnosis, which occurred at delivery, after 6 months of life, and after 2 years of life, respectively. They achieved and maintain virological suppression after 1, 6, and 7 months of therapy, respectively; then a switch strategy was performed with a two-drug regimen with DTG/3TC STR at the age of 7 years for the first child and at the age of 9 years for the second, while the third was switched to a DTG plus 3TC not STR, owing to weight requirements, at the age of 2 years and 10 months. All children maintained virological suppression at last follow-up visit (January 2024), showing an excellent growth curve and maintaining good adherence and tolerability to DTG plus 3TC. A two-drug regimen with DTG/3TC demonstrated efficacy in maintaining virological suppression in a switch strategy in these children, with important advantages such as better tolerability and comfort of taking a single tablet once daily.

PRESTIGIO RING "a 59-year-old man with multidrug resistant HIV-1 infection failing a regimen including dolutegravir, rilpivirine, atazanavir/cobicistat: successful treatment tailoring based on genotypic and phenotypic resistance tests".

Management of virological failure in heavily treatment-experienced people with multidrug-resistant (MDR) HIV infection is a serious clinical challenge. New drugs with novel mechanisms of action have recently been approved, and their use has improved the outcome of subjects with limited treatment options (LTO). In this setting, the choice of antiretroviral therapy (ART) should be tailored based on the pattern of resistance, treatment history and patients' individual characteristics. While genotypic resistance testing is the reference method for analysing residual drug susceptibility, phenotypic resistance testing can provide additional support when facing LTO. Herein, we present the case of a patient with MDR HIV-1 infection on virological failure enrolled in the PRESTIGIO Registry. The salvage ART regimen, which included drugs with novel mechanisms of action (MoA), was tailored to the patient's clinical characteristics and on the resistance pattern explored with genotypic and phenotypic investigation, allowing the achievement of viro-immunological success. The use of recently approved drugs with novel MoA, combined with an optimized background regimen, may also achieve virological suppression in people with LTO.

Racial and Ethnic Disparities in Initiation of Direct Oral Anticoagulants Among Medicare Beneficiaries.

Importance: The influence of race and ethnicity on initiation of direct oral anticoagulants (DOACs) is relatively understudied in Medicare data. Objective: To investigate disparities in the initiation of DOACs compared with warfarin by race, ethnicity, and social vulnerability. Design, Setting, and Participants: This retrospective cohort study used a 50% sample of Medicare fee-for-service data from January 1, 2010, to December 31, 2019 (mean patient enrollment duration, 7.7 years). Analysis took place between January 2023 and February 2024. A cohort of older adults (aged ≥65 years) with atrial fibrillation who newly initiated warfarin or DOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) was identified. Exposure: Patients were classified as non-Hispanic White, non-Hispanic Black, and Hispanic. Main Outcomes and Measures: The likelihood of starting use of DOACs compared with warfarin was modeled, adjusting for race, ethnicity, age, sex, county-level social vulnerability, and other clinical factors. Results: Among 950 698 anticoagulation initiations, consisting of 680 974 DOAC users and 269 724 warfarin users (mean [SD] age, 78.5 [7.6] years; 52.6% female), 5.2% were Black, 4.3% were Hispanic, and 86.7% were White. During the 10-year study period, DOAC use increased for all demographic groups. After adjustment, compared with White patients, Black patients were 23% less likely (adjusted odds ratio [AOR, 0.77; 95% CI, 0.75-0.79) and Hispanic patients were 13% less likely (AOR, 0.87; 95% CI, 0.85-0.89) to initiate DOAC use. Disparities in DOAC initiation were greatest among Black patients in the earlier years but attenuated during the study period. For instance, in 2010, the OR of Black patients initiating DOACs was 0.54 (95% CI, 0.50-0.57), attenuating linearly over time to 0.69 by 2013 (95% CI, 0.65-0.74) and 0.83 (95% CI, 0.78-0.89) by 2017. By 2019, these differences became nonsignificant (OR, 1.08; 95% CI, 0.99-1.18). Conclusions and Relevance: In this cohort study of Medicare patients with atrial fibrillation, Black and Hispanic patients were less likely to initiate DOACs for atrial fibrillation, although these differences diminished over time. Identifying the factors behind these early disparities is crucial for ensuring equitable access to novel therapies as they emerge for Black and Hispanic populations.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Low cabotegravir trough concentrations without oral lead-in in patients with HIV-1 switching to long-acting cabotegravir and rilpivirine.

In a cohort of 72 consecutive virologically-suppressed patients with HIV-1 switching to long-acting cabotegravir and rilpivirine, we observed low cabotegravir trough concentrations 1 and 3 months after the first injection, with a significant association with no oral lead-in at 1 month [odds ratio (OR) = 6.3 [95% confidence interval (CI) 1.7-29.5], P = 0.01] and three months (OR = 5.6 [95% CI 1.3-29.7], P = 0.03), and with high BMI at 1 month (OR = 1.3 [95% CI 1.1-1.6], P = 0.007).

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105.

Physiologically based absorption modeling to predict the bioequivalence of two apixaban formulations.

The equivalence of absorption rates and extents between generic drugs and their reference formulations is crucial for ensuring therapeutic comparability. Bioequivalence (BE) studies are widely utilized and play a pivotal role in substantiating the approval and promotional efforts for generic drugs. Virtual BE simulation is a valuable tool for mitigating risks and guiding clinical BE studies, thereby minimizing redundant in vivo BE assessments. Herein, we successfully developed a physiologically based absorption model for virtual BE simulations, which precisely predicts the BE of the apixaban test and reference formulations. The modeling results confirm that the test and reference formulations were bioequivalent under both fasted and fed conditions, consistent with clinical studies. This highlights the efficacy of physiologically based absorption modeling as a powerful tool for formulation screening and can be adopted as a methodological and risk assessment strategy to detect potential clinical BE risks.

Simulating BRAFV600E-MEK-ERK signalling dynamics in response to vertical inhibition treatment strategies.

In vertical inhibition treatment strategies, multiple components of an intracellular pathway are simultaneously inhibited. Vertical inhibition of the BRAFV600E-MEK-ERK signalling pathway is a standard of care for treating BRAFV600E-mutated melanoma where two targeted cancer drugs, a BRAFV600E-inhibitor, and a MEK inhibitor, are administered in combination. Targeted therapies have been linked to early onsets of drug resistance, and thus treatment strategies of higher complexities and lower doses have been proposed as alternatives to current clinical strategies. However, finding optimal complex, low-dose treatment strategies is a challenge, as it is possible to design more treatment strategies than are feasibly testable in experimental settings. To quantitatively address this challenge, we develop a mathematical model of BRAFV600E-MEK-ERK signalling dynamics in response to combinations of the BRAFV600E-inhibitor dabrafenib (DBF), the MEK inhibitor trametinib (TMT), and the ERK-inhibitor SCH772984 (SCH). From a model of the BRAFV600E-MEK-ERK pathway, and a set of molecular-level drug-protein interactions, we extract a system of chemical reactions that is parameterised by in vitro data and converted to a system of ordinary differential equations (ODEs) using the law of mass action. The ODEs are solved numerically to produce simulations of how pathway-component concentrations change over time in response to different treatment strategies, i.e., inhibitor combinations and doses. The model can thus be used to limit the search space for effective treatment strategies that target the BRAFV600E-MEK-ERK pathway and warrant further experimental investigation. The results demonstrate that DBF and DBF-TMT-SCH therapies show marked sensitivity to BRAFV600E concentrations in silico, whilst TMT and SCH monotherapies do not.

Unlocking the potential: exploring the impact of dolutegravir treatment on body mass index improvement in underweight adults with HIV in Malawi.

BACKGROUND: The introduction of dolutegravir (DTG) in treating HIV has shown enhanced efficacy and tolerability. This study examined changes in weight gain and body mass index (BMI) at 6- and 12-months after post-initiating antiretroviral therapy (ART), comparing people living with HIV (PLHIV) on DTG-based regimens with those on non-DTG-based regimens in Malawi. METHODS: Retrospective cohort data from 40 public health facilities in Malawi were used, including adult ART patients (aged ≥ 15 years) from January 2017 to March 2020. The primary outcomes were BMI changes/transitions, with secondary outcomes focused on estimating the proportion of mean weight gain > 10% post-ART initiation and BMI category transitions. Descriptive statistics and binomial regression were used to estimate the unadjusted and adjusted relative risks (RR) of weight gain of more than ( >) 10%. RESULTS: The study included 3,520 adult ART patients with baseline weight after ART initiation, predominantly female (62.7%) and aged 25-49 (61.1%), with a median age of 33 years (interquartile range (IQR), 23-42 years). These findings highlight the influence of age, ART history, and current regimen on weight gain. After 12months follow up, compared to those aged 15-24 years, individuals aged 25-49 had an Adjusted RR (ARR) of 0.5 (95% Confidence Interval (CI): 0.35-0.70), suggesting a 50% reduced likelihood of > 10% weight gain after post-ART initiation. Similarly, those aged 50 + had an ARR of 0.33 (95% CI: 0.20-0.58), indicating a 67% decreased likelihood compared to the youngest age group 15-24 years. This study highlights the positive impact of DTG-based regimens, revealing significant transitions from underweight to normal BMI categories at 6- and 12-months post-initiation. CONCLUSION: This study provides insights into weight gain patterns in patients on DTG-based regimens compared with those on non-DTG regimens. Younger individuals (15-24 years) exhibited higher odds of weight gain, suggesting a need for increased surveillance in this age group. These findings contribute to the understanding DTG's potential effects on weight gain, aiding clinical decision making. Further research is required to comprehensively understand the underlying mechanisms and long-term implications of weight gain in patients receiving DTG-based regimens.

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

BACKGROUND: The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. METHODS: In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. DISCUSSION: Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. TRIAL REGISTRATION: ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

Barriers to viral load suppression among adolescents living with HIV on anti-retroviral therapy: a retrospective study in Tanga, Tanzania.

BACKGROUND: Despite the decreased incidence of the human immunodeficiency virus (HIV) in Tanzania, the number of adolescents living with HIV is increasing. This study aimed to describe factors independently associated with viral load non-suppression among adolescents living with HIV (ALHIV) on ART in the Tanga region. METHODS: We conducted a retrospective study of routinely collected data from ALHIV on ART from October 2018 to April 2022. We extracted data from the Care and Treatment Clinics form number 2 (CTC2) database that included age, sex, BMI, World Health Organization HIV clinical disease stage, marital status, ART duration, viral load suppression, facility level, and Dolutegravir (DTG)-based regimen. We did descriptive analysis using frequencies to describe the study participants' socio-demographic and clinical characteristics. The Cox proportional hazard regression model was used to identify factors associated with viral load non-suppression (VLS). Viral load non-suppression was defined as viral load ≥ 1000 copies/ml. A total of 4735 ALHIV on ART were extracted from CTC2, then 2485 were excluded (2186 missed viral load results, 246 were lost to follow-up, and 53 deaths). RESULTS: 2250 ALHIV on ART were tested for viral load, of whom 2216 (98.62%) adolescents were on first-line ART, and 2024 (89.96%) participants were virally suppressed, while 226 (10.04%) were virally non-suppressed. In addition, 2131 (94.71%) of participants were using a DTG-based regimen; of them, 1969 (92.40%) were virally suppressed. Not using a DTG-based regimen (HR: 9.36, 95% CI 3.41-15.31) and dispensary facility level (HR: 3.61, 95% CI 1.44-7.03) were independently associated with increased hazard for viral load non-suppression. In addition, adolescents aged between 15 and 19 years are less likely to be virally suppressed (HR: 0.55, 95% CI 0.30-0.99). CONCLUSIONS: The dispensary facility level and not using a DTG-based regimen were significantly associated with viral load non-suppression. HIV intervention strategies should ensure a DTG-based regimen utilization in all adolescents living with HIV, and techniques used by higher-level health facilities should be disseminated to lower-level facilities.