INTRODUCTION:Janus kinase inhibitors (JAKIs) emerged as novel therapies for a wide range of autoimmune and myeloproliferative neoplasms. JAKIs have remarkable clinical effectiveness, but emerging safety concerns have sparked interest in precision dosing approaches and the role of therapeutic drug monitoring (TDM) remains largely unexplored. AREAS COVERED:This review summarizes the mechanisms of action, indications and adverse effects of approved JAKIs in Switzerland, namely, abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib. We discussed factors that impact the pharmacokinetics of JAKIs, as well as exposure-efficacy and toxicity relationships, to evaluate whether JAKIs are suitable candidates for TDM. Regulatory documents and a PubMed search using the terms 'drug monitoring,' 'pharmacokinetics,' and 'JAKIs (incl. abrocitinib, baricitinib, momelotinib, ritlecitinib, ruxolitinib, tofacitinib, and upadacitinib)' were used to compile data until March 2025. EXPERT OPINION:JAKIs meet the criteria for TDM as they have marked inter-individual pharmacokinetic variability, narrow therapeutic margins and exposure-response relationships. Implementing TDM in clinical practice requires to establish target concentration ranges associated with efficacy and toxicity, along with a better understanding of the pharmacokinetics of JAKIs in real-life settings.

Background: Inappropriate antibiotic use drives antimicrobial resistance and remains a global concern. Evidence suggests antibiotic use may be higher among malaria-negative patients compared to malaria-positive ones, but uncertainty persists, particularly in regions with varying malaria prevalence. This study measured antibiotic residuals in three Tanzanian regions with varying malaria epidemiology and analyzed factors influencing their presence. Methods: A cross-sectional household survey was conducted in 2015, covering a population of 6000 individuals across three regions of Tanzania. Dried blood spot samples from a subset of participants were analyzed using broad-range tandem mass spectrometry to detect residual antibiotics. Risk factors associated with antibiotic presence, including household healthcare-seeking behaviors, malaria testing, and other relevant variables, were evaluated. Results: The overall prevalence of residual antibiotics in the study population was 14.4% (438/3036; 95% CI: 11.4-15.8%). Stratified by malaria transmission intensity, antibiotic prevalence was 17.2% (95% CI: 12.9-17.2%) in Mwanza (low), 14.6% (95% CI: 10.6-15.0%) in Mbeya (moderate), and 11.2% (95% CI: 7.9-11.6%) in Mtwara (high). Trimethoprim was the most frequently detected antibiotic (6.1%), followed by sulfamethoxazole (4.4%) and penicillin V (0.001%). Conclusions: Residual antibiotic prevalence did not directly correlate with malaria endemicity but was influenced by healthcare practices, including co-prescription of antibiotics and antimalarials. The higher antibiotic use in malaria-negative cases highlights the need for improved diagnostics to reduce unnecessary use and mitigate antimicrobial resistance in malaria-endemic areas.

BackgroundLevosimendan is used off-label in pediatrics and pharmacokinetic (PK) data in this population are scarce. The only study in critically ill patients on extracorporeal membrane oxygenation (ECMO) showed altered PK parameters. Our study aimed to characterize the PK profile of levosimendan and its metabolites in critically ill children on ECMO and assess the adequacy of current dosing practices.MethodsWe conducted a prospective observational PK study in a Swiss tertiary pediatric intensive care unit. Children on ECMO for hemodynamic failure receiving continuous levosimendan infusion (0.1 µg/kg/min for 48 h) were included.ResultsFive full-term newborns and one infant were included (median age 24 days). A total of seven sets of eight blood samples were collected. Median (range) steady-state levosimendan concentration was 16.68 (7.92–18.88) ng/ml. Non-compartmental analysis revealed a median clearance (CL) of 5.99 (5.18–11.32) ml/min/kg, volume of distribution (Vd) of 1.48 (1.07–6.27) L/kg, and elimination half-life of 4.59 (3.40–6.50) hours. ECMO and body composition of our patients, mostly post-cardiac surgery neonates, might explain the increased CL and Vd in our population compared to older children not on ECMO (CL 3.60 ml/min/kg, Vd 0.35 L/kg). Active metabolite OR-1896 concentrations were markedly lower than in neonates not on ECMO.ConclusionsIn our cohort of critically ill children on ECMO, augmented CL and Vd were associated with low levosimendan concentrations. This suggests that dosage should be increased in this context, to achieve optimal exposure of levosimendan and its active metabolite.

Introduction Saliva is a promising option for therapeutic drug monitoring, with studies since the 1970s indicating a good correlation between plasma and saliva levels for early anti-seizure medications, although limited data exist for newer generation drugs. Objectives To evaluate the reliability and predictive power of saliva as a minimally invasive surrogate marker of plasma concentration for the routine therapeutic drug monitoring (TDM) of newer anti-seizure medications (ASM). Methods We collected blood samples at steady state in patients at least 6h post-dose, paired with unstimulated saliva samples. We evaluated the correlation between plasma and saliva drug levels and the positive and negative predictive value for plasma values extrapolation from saliva levels. A very low saliva level was defined as below half the plasma lower reference limit. Results 294 adult patients (53% male) with a mean age of 40 (SD: 16) were enrolled and 589 paired saliva-plasma samples were quantified. The highest significant correlations between saliva and plasma were observed for zonisamide (R2: 0.92) perampanel (0.91), brivaracetam (0.87), followed by topiramate, lamotrigine, lacosamide (0.76-0.68), and rufinamide, levetiracetam, pregabalin (0.63-0.55). No significant correlation was found for the active mono-hydroxy derivative of oxcarbazepine. Despite a good correlation coefficient, the correlations between saliva and plasma levels were generally loose, resulting in a broad predicted range of plasma levels for a given saliva level. Nonetheless, very low saliva levels exhibited strong specificity in predicting low plasma levels, with 87% to 100% accuracy, and when saliva levels fell below the limit of quantification, all corresponding plasma levels were below reference ranges. Conclusions This large newer ASM paired plasma-saliva collection allows to precise the potential use of saliva in the management of epilepsy, especially for commonly used ASM such as lamotrigine and levetiracetam. Although they correlate well, extrapolating plasma levels from saliva samples is still an imprecise approximation, making it inadequate for fine dosage adjustments. Yet, a very low saliva level has an appreciable discriminative ability for low plasma level. Unstimulated saliva represents a convenient non-invasive alternative to plasma, to readily identify compliance issues or major drug-drug interactions.

Introduction: Inappropriate antibiotic use is a big driver of bacterial antimicrobial resistance, and an increasing problem worldwide. Antibiotic use has sometimes been found to be more frequent by patients without malaria than patients with malaria. However, much uncertainty still exists, especially in places with varying malaria prevalence. In this study, the residuals of commonly used antibiotics in Tanzania were measured in samples collected from subjects living in three regions with different malaria epidemiology. Methods: A cross sectional household survey was conducted in 2015 to assess antimalarial medicine use in a population of 6000 individuals in three regions. Antibiotics residuals were measured in dried blood spots of a subset of people using broad-range tandem mass spectrometry technology. Risk factors for presence of antibiotic residuals were evaluated, including household healthcare seeking behaviors, malaria testing and other potential variables. Results: The overall prevalence of residual antibiotics in blood in the studied population was 14.4% (438/3036) with 95% CI of 11.4 – 15.8%. Stratifying by malaria transmission intensity, the antibiotic prevalence was 17.2% (95% CI: 12.9 - 17.2%) in Mwanza (low), 14.6% (95% CI: 10.6-15.0 %) in Mbeya (moderate), and 11.2% (95% CI: 7.9–11.6%) in Mtwara (high). Trimethoprim was the medication most often detected (6.1%) followed by sulfamethoxazole (4.4%), and penicillin V (0.001%).

Levosimendan is a positive inotrope and vasodilator used in patients with acute and chronic decompensated heart failure. It is metabolized into OR-1855 (inactive metabolite), which is further acetylated into OR-1896 (active metabolite having a prolonged half-life, hence a sustained effect). Levosimendan represents a valuable alternative to traditional inotropes with broad clinical applications in critically ill patients with cardiogenic shock, advanced heart failure and post-cardiac surgery. However, while levosimendan demonstrates dose- dependent hemodynamic effects, its pharmacokinetics has not yet been investigated in adult critically ill patients, a vulnerable population characterized by complex and unstable conditions that may significantly alter drug disposition. Therefore, pharmacokinetics studies of levosimendan and metabolites in critically ill patients require a reliable and sensitive quantification method. We developed and validated a highly sensitive method using ultra-high-performance liquid-chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) for the quantification of levosimendan, OR-1855 and OR-1896 in human plasma. To achieve the required analytical sensitivity, plasma sample preparation included protein precipitation with acetonitrile, subsequent supernatant's evaporation to dryness under nitrogen, and reconstitution of the solid residues with a solution of H2O:MeOH 4:1, followed by a 40 mu L-aliquot injection into the LC column. Chromatographic separation of the three analytes was achieved in a 6-minute run in gradient mode, using an Acquity UPLC BEH C18 1.7 mu m, 2.1 x 150 mm column. The method was extensively validated according to international bioanalytical assay guidelines, on a clinically relevant concentration range of 0.1-100 ng/mL, for each analyte. Considering these very low concentrations, the assay showed excellent performances in terms of trueness (94.3-105.3 %), repeatability (1.9-7.2 %) and intermediate fidelity (2.3-9.7 %). Of note, during our ex vivo studies on whole blood samples stability, acetylation of the metabolite OR-1855 into the active OR-1896 metabolite was observed in the presence of red blood cells. The UHPLC method is being applied for a prospective observational pharmacokinetics study of levosimendan in patients undergoing extracorporeal membrane oxygenation support. The benefit of levosimendan therapeutic drug monitoring in intensive care patients remains to be assessed.

Background Model-informed precision dosing (MIPD) combines population pharmacokinetic knowledge with therapeutic drug monitoring (TDM) to optimize dosage adjustment. It could improve target concentration attainment over empirical TDM, still widely practised for broad-spectrum antibiotics. Objectives To evaluate the respective performance of TDM and MIPD in achieving target piperacillin exposure. Methods Measurements from 80 courses of intermittent piperacillin infusions, each with two TDM samples, were retrospectively submitted to our MIPD software TUCUXI. We considered six dosage adjustment strategies: identical dosage for all (4000 mg q8h), actual initial dosage (chart-based), actual empirical adjustment following first TDM, a priori MIPD-based dosage, a posteriori MIPD-based adjustment after first TDM and MIPD including both TDM measurements. Dosing strategies were compared regarding daily dosage, trough levels distribution and PTA (with target trough 8-32 mg/L). Results Median trough concentration fell within 8-32 mg/L for all strategies except a priori MIPD-based dosage (42 mg/L). Distributions of trough concentrations predicted with the six dosage adjustment strategies showed significant differences, with both a posteriori MIPD-based strategies best reducing their standard deviation (P < 0.001). PTA of 32%, 32%, 55%, 29%, 83% and 94% were estimated, respectively for the six strategies (P < 0.001). Poor performance of a priori MIPD-based dosage did not hinder a posteriori MIPD-based strategies from significantly improving target attainment. Conclusions Whilst empirical TDM improves exposure standardization and target attainment compared with no TDM, MIPD can still bring further improvement. Prospective trials remain warranted to confirm MIPD benefits not only on target attainment but also on clinical endpoints.

We aimed to compare the antibiotic concentrations obtained using the volumetric absorptive microsampling (VAMS) devices with those determined in plasma from conventional venous blood collected within the frame of a pharmacokinetic study of amoxicillin (AMO), metronidazole (MET), azithromycin (AZI), commonly used for periodontal treatment. The suitability and overall, acceptability of the VAMS approach was also ascertained by both participants of the pilot study and dentist practitioners. Twelve volunteers (6 subjects without periodontal problems (PH), and 6 individuals affected with periodontitis (PP)) were administered 500 mg each of amoxicillin, metronidazole, and azithromycin. Paired venous blood (VB) and capillary VAMS samples were collected at 2-, 6-,10-, 24-, 48- and 96-hours post-antibiotics administration. Antibiotic concentrations were determined using multiplex liquid chromatography coupled tandem mass spectrometry (LC-MS/MS). Statistical analyses included Mann-Whitney U tests and t-tests. Significant differences in antibiotic concentrations were observed between VAMS and venous blood (VB) collection methods, across different time points for the three antibiotics (p < 0.05). AMO concentrations in VB were 3.5-fold higher (p < 0.01) than in VAMS at early time points (2, 6, 10 h (h)). MET levels in VB were 1.5-fold higher than in VAMS at 2 h and 6 h, (p < 0.01), but this difference disappeared after 10 h. Alternately, while AZI levels were similar in VB and VAMs 2 h after administration, AZI concentrations in VB and VAMS declined non parallelly, with VB levels decreasing to about 60 to 25

BACKGROUND:This review re-evaluates therapeutic drug monitoring (TDM) by comparing the current analytical and subsequent clinical interpretation capabilities of hospital or community medical laboratories with the emerging potential of point-of-care (POC) devices, which could become increasingly utilized in hospital wards, day-hospital units, and outpatient clinic settings. METHODS:A narrative review was conducted to identify publications that best illustrate the current trends in the development of POC TDM. RESULTS:The latest scientific and technical literature indicates that POC devices for determining drug concentrations in clinical samples are approaching the market. Several technologies are now available to develop portable sensors capable of rapidly returning concentration measurements. Interfacing these methods with artificial intelligence-based pattern recognition may enhance the identification and quantification of drugs. However, once the drug concentration is accurately measured using a portable device, dosage adjustments require consideration of the drug's pharmacokinetics and the patient's characteristics. This is accounted for in the mathematical approaches underlying model-informed precision dosing, which consider inter- and intra-individual variability and provide recommendations for treatment adjustments. These complexities necessitate the use of digital technologies, including graphical interfaces, machine learning approaches, and secure connectivity, to enhance the application of TDM in clinical practice. CONCLUSIONS:Promising emerging technologies have considerable potential to expand TDM to cover a wide range of drugs, making precision medicine accessible to many patients.

INTRODUCTION:The correlation between plasma and saliva concentration of anti-seizure medication (ASM) is well established, but variability limits the acceptance of saliva-based Therapeutic Drug Monitoring (TDM). We analysed the correlation between salivary levetiracetam and lamotrigine levels, and efficacy and tolerability. METHODS:Blood and saliva samples were collected over two years. Seizure freedom was defined as three times the longest pre-treatment inter-seizure interval or at least one year seizure-free without treatment changes. Adverse effects were assessed during visits. Lamotrigine and levetiracetam saliva and plasma concentrations were compared across groups based on treatment response and adverse effects. Response and adverse events predictors were analysed using binary logistic regression. RESULTS:Among 296 adults with epilepsy, 84 (28 %) achieved seizure freedom. These patients were older, predominantly on monotherapy, and underwent fewer ASM trials. 27 patients (9 %) reported adverse effects and were older at epilepsy onset. Seizure-free lamotrigine users had a lower dosage (median 2 vs 3.3 mg/kg, p = 0.07), and lower plasma and salivary concentrations (median plasma 2.6 vs 3.9 mg/L, p = 0.026; median saliva 1.4 vs 2.4 mg/L, p = 0.011). No association was found between lamotrigine dosage, levels, and adverse events. Levetiracetam users reporting side effects had higher salivary concentrations (median 20 vs 14.40 mg/L, p = 0.04), while seizure-free individuals showed no difference in salivary levels, although dosages and plasma levels differed. CONCLUSION:This study highlights the clinical relevance of saliva TDM, linking salivary drug levels to treatment response for lamotrigine and adverse effects for levetiracetam. Salivary ASMs levels may complement plasma TDM, enhancing individualised treatment.

BackgroundJanus kinase inhibitors (JAKIs) are small molecules used orally to treat inflammatory and hematological disorders. They have demonstrated impressive efficacy across multiple indications. However, concerns have emerged regarding their safety profile. Despite their growing clinical use, therapeutic drug monitoring is not yet established for JAKIs, but it could help address exposure-dependent efficacy and tolerability issues through individualized treatment approaches. ObjectiveThis protocol aims to characterize the pharmacokinetics of the 6 most prescribed JAKIs in Switzerland (abrocitinib, baricitinib, fedratinib, ruxolitinib, tofacitinib, and upadacitinib) and identify factors influencing drug exposure. It seeks to explore exposure-response relationships to assess the impact of drug exposure markers on efficacy and safety. Ultimately, these findings will contribute to establishing therapeutic intervals. MethodsThis prospective observational study, conducted throughout Switzerland, was approved by the Cantonal Ethics Committee in August 2023. Consenting adults (aged ≥18 years) who are capable of judgment and who are prescribed JAKIs are enrolled in the study, either for sparse sampling during routine medical visits to collect trough or random plasma concentrations or for a detailed pharmacokinetic substudy involving serial blood sampling over an 8-hour period. The characterization of JAKI pharmacokinetics, including associated variability and the effect of specific covariates, such as age, body weight, BMI, sex, disease type, drug-drug interactions, or concomitant pathophysiological conditions, will be performed using nonlinear mixed effect modeling techniques. Relationships between JAKI exposure and efficacy and safety will be assessed. ResultsBy August 2024, a total of 276 blood samples were collected from 107 patients, the majority being female individuals (n=62, 57.9%). The patients had a median age of 51 (range 17-87) years and a median body weight of 69 (range 39-132) kg. Most patients recruited were taking ruxolitinib (n=44, 41.1%), upadacitinib (n=39, 36.4%), or baricitinib (n=11, 10.3%). ConclusionsThe framework of the study will allow the characterization of the pharmacokinetic profiles of JAKIs and their variability in real-world conditions. On the basis of novel therapeutic drug monitoring approaches, we expect to explore the relationship between drug exposure, treatment response, and tolerability, providing essential information for precise dose optimization. International Registered Report Identifier (IRRID)RR1-10.2196/70312

Background Invasive fungal infections (IFIs) are severe and difficult-to-treat infections affecting immunocompromised patients. Antifungal drug penetration at the site of infection is critical for outcome and may be difficult to achieve. Data about antifungal drug distribution in infected human tissues under real circumstances of IFI are scarce.Methods Multiple samples were obtained from soft tissue abscesses of a lung transplant patient with Candida albicans invasive candidiasis who underwent recurrent procedures of drainage, while receiving different consecutive courses of antifungal therapy [itraconazole (ITC), fluconazole, caspofungin]. Antifungal drug concentrations were measured simultaneously at the site of infection (surrounding inflammatory tissue and fluid content of the abscess) and in plasma for calculation of the tissue/plasma ratio (R). The concentration within the infected tissue was interpreted as appropriate if it was equal or superior to the MIC of the causal pathogen.Results A total of 30 tissue samples were collected for measurements of ITC (n = 12), fluconazole (n = 17) and caspofungin (n = 1). Variable concentrations were observed in the surrounding tissue of the lesions with median R of 2.79 (range 0.51-15.9) for ITC and 0.94 (0.21-1.37) for fluconazole. Concentrations ranges within the fluid content of the abscesses were 0.39-1.83 for ITC, 0.66-1.02 for fluconazole and 0.23 (single value) for caspofungin. The pharmacodynamic target (tissue concentration >= MIC) was achieved in all samples for all three antifungal drugs.Conclusions This unique dataset of antifungal drug penetration in infected human soft tissue abscesses suggests that ITC, fluconazole and caspofungin could achieve appropriate concentrations in soft tissue abscesses.

BackgroundThe pharmacokinetics of long-acting rilpivirine has mostly been studied in clinical trials, which do not fully address the uncertainties that arise in routine clinical situations.Aims and methodsOur population analysis aims to establish percentile curves for rilpivirine concentrations in people with HIV (PWH) followed-up in a routine clinical setting, while identifying patient-related factors that may influence rilpivirine exposure. A total of 238 PWH enrolled in our nationwide multicenter observational study contributed to 1038 concentrations (186 and 852 concentrations after oral and intramuscular injection, respectively).ResultsRilpivirine pharmacokinetics were best described by a two-compartment model with an oral to intramuscular relative bioavailability factor. A simple zero-order absorption process was retained for oral administration while a parallel first-order absorption was used for intramuscular administration, with 27.6% of the dose released via a fast absorption pathway and the remaining fraction via a slow absorption pathway. Our model estimated that long-acting rilpivirine reaches steady-state after 2.5 years and has an elimination half-life of 18 weeks, consistent with published estimates. In females, a 45.6% reduction in the proportion of the dose absorbed via the rapid absorption pathway was observed. However, this resulted in no more than 15% difference in trough concentrations (Ctrough) compared to males, which was not considered to be clinically relevant.ConclusionOverall, our model-based simulations showed that only approximately 50% of long-acting rilpivirine Ctrough would be above the 50 ng/mL threshold associated with optimal therapeutic response, while approximately 85% of Ctrough would be above the first quartile of concentrations observed in Phase III trials (32 ng/mL).

HIV cure has been reported for five individuals who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with cells from CCR5 Delta 32 homozygous donors. By contrast, viral rebound has occurred in other people living with HIV who interrupted antiretroviral treatment after undergoing allo-HSCT, with cells mostly from wild-type CCR5 donors. Here we report the case of a male individual who has achieved durable HIV remission following allo-HSCT with cells from an unrelated HLA-matched (9 of 10 matching for HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 alleles) wild-type CCR5 donor to treat an extramedullary myeloid tumor. To date, plasma viral load has remained undetectable for 32 months after the interruption of antiretroviral treatment. Treatment with ruxolitinib has been maintained during this period to treat chronic graft-versus-host disease. Low levels of proviral DNA were detected sporadically after allo-HSCT, including defective but not intact HIV DNA. No virus could be amplified in cultures of CD4+ T cells obtained after antiretroviral treatment interruption, while CD4+ T cells remained susceptible to HIV-1 infection in vitro. Declines in HIV antibodies and undetectable HIV-specific T cell responses further corroborate the absence of viral rebound after antiretroviral treatment interruption. These results suggest that HIV remission could be achieved in the context of allo-HSCT with wild-type CCR5. HIV remission was achieved for 32 months after allogeneic hematopoietic stem cell transplantation with wild-type CCR5 donor cells.

Objectives: Children account for a significant proportion of antibiotic consumption in low- and middleincome countries, with overuse occurring in formal and informal health sectors. This study assessed the prevalence and predictors of residual antibiotics in the blood of children in the Mbeya and Morogoro regions of Tanzania. Methods: The cross-sectional community-based survey used two-stage cluster sampling to include children aged under 15 years. For each child, information on recent illness, healthcare-seeking behaviour, and use of antibiotics, as well as a dried blood spot sample, were collected. The samples underwent tandem mass spectrometry analysis to quantify the concentrations of 15 common antibiotics. Associations between survey variables and the presence of residual antibiotics were assessed using mixedeffects logistic regression. Results: In total, 1742 children were surveyed, and 1699 analysed. The overall prevalence of residual antibiotics in the blood samples was 17.4% (296/1699), the highest among children under the age of 5 years. The most frequently detected antibiotics were trimethoprim (144/1699; 8.5%), sulfamethoxazole (102/1699; 6.0%), metronidazole (61/1699; 3.6%), and amoxicillin (43/1699; 2.5%). The strongest predictors of residual antibiotics in the blood were observed presence of antibiotics at home (adjusted odds ratio [aOR] = 2.9; 95% CI, 2.0-4.1) and reported consumption of antibiotics in the last 2 weeks (aOR = 2.5; 95% CI, 1.6-3.9). However, half (145/296) of the children who had residual antibiotics in their blood, some with multiple antibiotics, had no reported history of illness or antibiotic consumption in the last 2 weeks, and antibiotics were not found at home. Discussion: This study demonstrated a high prevalence of antibiotic exposure among children in Tanzanian communities, albeit likely underestimated, especially for compounds with short half-lives. A significant proportion of antibiotic exposure was unexplained and may have been due to unreported selfmedication or environmental pathways. Incorporating biomonitoring into surveillance strategies can help better understand exposure patterns and design antibiotic stewardship interventions. Theopista Lotto, Clin Microbiol Infect 2024;30:1042 (c) 2024 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY license (http://creativecommons.org/ licenses/by/4.0/).

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.