Suboptimal Treatment Adherence Research Articles

MARVEL-minimising the emergence and dissemination of HIV-1 drug resistance in Portuguese-speaking African Countries (PALOP): low-cost portable NGS platform for HIV-1 surveillance in Africa

BackgroundHIV-1 infections remain a global public health concern. Scaled-up antiretroviral treatment (ART) is crucial for reducing morbidity and mortality related to HIV/AIDS. The emergence of drug-resistance mutations (DRMs) compromises viral suppression and contributes to the continued HIV-1 transmission. Several reports indicate a recent increase in acquired (ADR) and transmitted (TDR) drug resistance in Africa, probably linked to the lack of implementation of HIV drug resistance (HIVDR) testing and suboptimal treatment adherence. Herein, we will develop a low-cost protocol using third-generation sequencing (Oxford Nanopore Technology) for HIV-1 surveillance in Portuguese-speaking African Countries - PALOP [Angola (AO), Cape Verde (CV), Mozambique (MZ), and Sao Tome & Principe (STP)].MethodsThis is a multicentric cross-sectional study that includes around 600 adult patients newly diagnosed with HIV-1 in the PALOP. An epidemiological questionnaire previously validated by our research team will be used to collect sociodemographic and clinical data. Also, whole blood samples will be collected and the plasma samples will be subjected to drug resistance testing using an in-house low-cost NGS protocol. Data analysis will involve bioinformatics, biostatistics and machine learning techniques to generate accurate and up-to-date information about HIV-1 genetic diversity, ADR and TDR.DiscussionThe implementation of this low-cost NGS platform for HIV-1 surveillance in the PALOP will allow: (i) to increase DRM surveillance capacity in resource-limited settings; (ii) to understand the pattern and determinants of dissemination of resistant HIV-1 strains; and (iii) to promote the development of technical and scientific skills of African researchers for genomic surveillance of viral pathogens and bioinformatics analysis. These objectives will contribute to reinforcing the capacity to combat HIV infection in Africa by optimizing the selection of ART regimens, improving viral suppression, and reducing ADR or TDR prevalence in PALOPs, with relevant implications for public health.

Intramuscular versus enteral penicillin prophylaxis to prevent progression of rheumatic heart disease: Study protocol for a noninferiority randomized trial (the GOALIE trial)

Rheumatic Heart Disease (RHD) persists as a major cardiovascular driver of mortality and morbidity among young people in low-and middle-income countries. Secondary antibiotic prophylaxis (SAP) with penicillin remains the cornerstone of RHD control, however, suboptimal treatment adherence undermines most secondary prevention programs. Many of the barriers to optimal SAP adherence are specific to the intramuscular form of penicillin and may potentially be overcome by use of oral penicillin. This noninferiority trial is comparing the efficacy of intramuscular to oral penicillin SAP to prevent progression of mild RHD at 2 years. The Intramuscular vs Enteral Penicillin Prophylaxis to Prevent Progression of Rheumatic Heart Disease (GOALIE) trial is randomizing Ugandan children aged 5 to 17 years identified by echocardiographic screening with mild RHD (Stage A or B as defined by 2023 World Heart Federation criteria) to Benzathine Benzyl Penicillin G (BPG arm, every-28-day intramuscular penicillin) or Phenoxymethyl Penicillin (Pen V arm, twice daily oral penicillin) for a period of 2 years. A blinded echocardiography adjudication panel of 3 RHD experts and 2 cardiologists is determining the echocardiographic stage of RHD at enrollment and will do the same at study completion by consensus review. Treatment adherence and study retention are supported through peer support groups and case management strategies. The primary outcome is the proportion of children in the Pen V arm who progress to more advanced RHD compared to those in the BPG arm. Secondary outcomes are patient-reported outcomes (treatment acceptance, satisfaction, and health related quality of life), costs, and cost-effectiveness of oral compared to intramuscular penicillin prophylaxis for RHD. A total sample size of 1,004 participants will provide 90% power to demonstrate noninferiority using a margin of 4% with allowance for 7% loss to follow-up. Participant enrollment commenced in October 2023 and final participant follow-up is expected in December 2026. The graphical abstract (Fig. 1) summarizes the flow of echocardiographic screening, participant enrollment and follow-up. The GOALIE trial is critical in global efforts to refine a pragmatic approach to secondary prevention for RHD control. GOALIE insists that the inferiority of oral penicillin be proven contemporarily and against the most important near-term clinical outcome of progression of RHD severity. This work also considers other factors that could influence the adoption of oral prophylaxis and change the calculus for acceptable efficacy including patient-reported outcomes and costs. ClinicalTrials.gov: NCT05693545.

Comparison of medication adherence in patients with type 2 diabetes mellitus: a pre and post study

Background: Type 2 diabetes mellitus refers to a group of heterogeneous disorders with the common elements of chronic hyperglycemia. Diabetes medications play a crucial role in lowering blood sugar levels. The study aims to compare medication adherence in patients with type 2 diabetes mellitus from urban and rural areas during pre and post visit. Methods: This pre and post-study was conducted from March to August 2022. A total of 104 participants were enrolled. Details have been obtained through data collection form. Medication adherence was measured using Hill-Bone medication adherence scale, and patient education was provided through leaflet. Results: The study included 54 females and 50 males. The correlation between medication adherence versus disease knowledge and drug knowledge was found out using Pearson’s correlation and the result is statistically significant. The medication adherence was found to be increased by 17.3% and 21.2% in rural and urban areas respectively. Inadequate follow-up and financial barriers were most accounted for medication non-adherence. Conclusions: The majority of type 2 diabetes patients have suboptimal treatment adherence which is associated with poor blood sugar control. We clinical pharmacists can tackle this problem of adherence through quality patient education.

A Comprehensive Literature Review of Treatment-Emergent Integrase Resistance with Dolutegravir-Based Regimens in Real-World Settings.

After a decade of dolutegravir (DTG) use in various antiretroviral therapy combinations and in diverse populations globally, it is critical to identify HIV strains with reduced drug susceptibility and monitor emergent resistance in people living with HIV who experience virologic failure while on DTG-based regimens. We searched the PubMed, Embase, and Cochrane databases to identify studies that reported DTG resistance-associated mutations (RAMs) emerging under selection pressure. Our review showed that RAMs conferring resistance to DTG were rare in 2-drug and 3-drug regimens used in real-world cohorts, corroborating data from clinical trials. The potency of DTG in maintaining virologic suppression was demonstrated, even in cases of pre-existing resistance to companion drugs in the regimen. Estimates of DTG RAMs depended on the population and certain risk factors, including monotherapy, baseline resistance or lack of genotypic testing, treatment history and prior virologic failure, and suboptimal treatment adherence. The RAMs detected after virologic failure, often in heavily treatment-experienced individuals with prior exposure to integrase strand transfer inhibitors, were G118R, E138K, G140A/C/R/S, Q148H/K/R, N155H, and R263K. Overall, these data highlight the durable effectiveness and high barrier to resistance of DTG as part of combination antiretroviral therapy in a wide variety of settings.

Enhancing panic disorder treatment with mobile-aided case management: an exploratory study based on a 3-year cohort analysis.

Individuals with panic disorder frequently face ongoing symptoms, suboptimal treatment adherence, and increased relapse rates. Although mobile health interventions have shown promise in improving treatment outcomes for numerous mental health conditions, their effectiveness, specifically for panic disorder, has yet to be determined. This study investigates the effects of a mobile-aided case management program on symptom reduction and quality of care among individuals with panic disorder. This 3-year cohort study enrolled 138 participants diagnosed with panic disorder. One hundred and eight participants joined the mobile-aided case management group and 30 in the treatment-as-usual group. Data were collected at baseline, 3-month, 6-month, and 12-month treatment checkpoints using self-report questionnaires, in-depth interviews, direct observation, and medical record analysis. During the maintenance treatment phase, the mobile-assisted case management group decreased both panic severity (p = 0.008) and state anxiety (p = 0.016) more than the control group at 6 months. Participants who underwent case management experienced enhanced control over panic symptoms, heightened self-awareness, and elevated interpersonal support. The mobile-aided case management is beneficial in managing panic disorder, especially maintenance treatment.

Treatment-emergent reverse transcriptase resistance during antiretroviral therapy with bictegravir, tenofovir alafenamide, and emtricitabine: A case series.

Bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) is a complete regimen for the treatment of HIV with a high barrier to resistance and few reported cases of treatment failure. We present three cases of treatment-emergent resistance to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in patients with suboptimal treatment adherence and assess whether the resistance-associated mutations were present before BIC/TAF/FTC initiation or emerged during therapy. We used genotypic drug resistance testing by Sanger sequencing to identify emergent resistance mutations in plasma viral load specimens collected after combination antiretroviral therapy initiation in all participants. Additionally, we performed ultra-deep sequencing by Illumina MiSeq on the earliest available plasma HIV-1 viral load specimen and on any available specimens closest in time to the initiation of BIC/TAF/FTC therapy to identify low-abundance resistance mutations present in the viral quasispecies. All three participants developed NRTI resistance after prolonged exposure and incomplete adherence to BIC/TAF/FTC. The T69N, K70E, M184I, and/or T215I mutations identified in clinical samples at the time of virological failure were not present on deep sequencing of either baseline samples or samples collected before BIC/TAF/FTC initiation. Despite a generally high genetic barrier to resistance, NRTI resistance-associated mutations may emerge during therapy with BIC/TAF/FTC in the setting of suboptimal adherence.

P084 The relationship between self-reported adherence, drug levels and tumour necrosis factor inhibitor response in psoriatic arthritis

Abstract Background/Aims It is not currently possible to accurately predict tumour necrosis factor inhibitor (TNF-i) response in psoriatic arthritis (PsA). In rheumatoid arthritis, suboptimal adherence to TNF-i and reduced drug levels have been associated with decreased response. Suboptimal treatment adherence (16%-81%) has been reported in PsA although little is known about the impact on TNF-i response. Self-reported adherence may be biased, but direct drug measurements offer an objective adherence evaluation. The objective of this study is to assess the relationship between self-reported adherence, drug levels, and drug response to TNF-i in PsA. Methods Blood samples and adherence questionnaires were collected at 3, 6 and 12 months for PsA patients prescribed biologic or targeted synthetic anti-rheumatic drugs in a UK multi-centre observational study (OUTPASS). Self-reported adherence was measured using two previously validated questionnaires (MARS5 and Treatment). Adherence was classified as self-reporting never missing or delaying a dose, unless medically advised. Adalimumab (ADA) and etanercept (ETN) drug levels were measured at 3 and 6 months using commercially available ELISAs. Clinical response was assessed using PsARC and ΔDAS28 between baseline and 3, 6 and 12 months. Univariate regression and general estimating equations were used to assess associations across timepoints. Results In the OUTPASS cohort (46% ADA, 40% ETN), 42% of patients self-reported non-adherence within the first 12 months of treatment. Patients with self-reported non-adherence at 6 months using the MARS5 questionnaire were significantly less likely to achieve a PsARC response at 6 months [odds ratio (OR)=0.40, P = 0.047] in univariate regression. Non-adherence, reported using the Treatment questionnaire, was associated with decreased PsARC response over 12 months [OR = 0.52, P = 0.031]. There was no association (P > 0.05) between whether a patient returned a self-reported adherence questionnaire and response. Drug levels at 3 months (n = 70 (ADA), 73 (ETN)) were associated with drug levels at 6 months (n = 61 (ADA), 67 (ETN)) for both ADA [β = 0.47, P = 0.001] and ETN [β = 0.41, P = 0.018] paired samples. Higher 3-month ADA levels were associated with increased ΔDAS28 response at 3 months [β = 0.11, P = 0.036] and PsARC response at 12 months [OR = 1.39, P = 0.028]. Higher 3-month ETN levels were associated with increased PsARC response at 3 months [OR = 1.50, P = 0.026]. Increased ADA levels were associated with improved ΔDAS28 over 12 months [β = 0.07, P = 0.001] and higher ETN levels associated with enhanced PsARC response [OR = 1.17, P = 0.022] over 12 months. Levels of neither drug were associated (P > 0.05) with any self-reported adherence measures at any time point. Conclusion There was no association between self-reported adherence and TNF-i drug levels in ADA or ETN-treated PsA patients. Objectively measured adherence via drug level measurements were more strongly associated with drug response than self-reported measures, particularly using ΔDAS28 as the measure of response. Disclosure P.D.K. Curry: None. A.P. Morris: None. M. Jani: None. H. Chinoy: Grants/research support; HC received grant support from Eli Lilly and UCB. A. Barton: Grants/research support; AB has received fees/grant awards from Galapagos, Scipher Medicine, Roche-Chugai, Pfizer and BMS. J. Bluett: Grants/research support; JB has received a research grant award from Pfizer. Other; JB has received travel/conference fees from UCB, Pfizer and Eli Lilly.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

Abstract P4-07-58: Adjuvant Endocrine Therapy adherence in Breast Cancer patients and the Brazilian National Health System

Abstract Introduction: Breast Cancer is one of the most prevalent malignant disease in women and its first line neo- and/or adjuvant treatment on hormone positive (HR+) subtypes is the endocrine therapy. Even though Adjuvant Endocrine Therapy (AET) had significantly increased overall survival in the long-run, some studies have reported suboptimal treatment adherence rates, varying from 40-95.7%. One possible cause for this great variability on AET adherence is the patients’ expenses on treatment. Recent studies have demonstrated that as the cost of treatment increases the treatment adherence decreases. Nonetheless, as far as the authors have searched, no studies have tried to understand such relationship in Brazil, where medications can be taken without any out-of-pocket expenses through the Sistema Único de Saúde (SUS), or through Health insurance companies; and through direct out-of-pocket expenses. Methods: This was an observational cross-sectional pilot study, carried out with an online questionnaire applied to patients from the Centro de Tratamento Oncológico Pro Onco [Pro Onco Oncological Treatment Center] and Centro de Apoio ao Paciente com Câncer de Londrina [Londrina Cancer Support Center] (State of Paraná, Brazil). The questionnaire applied in this study included objective questions that aimed to understand the systemic endocrine therapy adherence among Breast Cancer patients. In order to do that, the Morisky-Green (MG) test was used. A linear regression model was built using the MG test as dependent variable, and how the patients obtained the drugs as independent variable, controlled by other sociodemographic and clinical covariates. Results: Between December 2021 and March 2022, 95 patients were included in this study. Mean age was 50.71 (SD = 10.00) and mean age at diagnosis was 45.86 (SD = 8.66). Patients obtained the drugs mainly via Health Insurance (45 patients or 47.37%), followed by the SUS (44 patients or 46.32%) and private health expenses (6 patients or 6.32%). It was found that how the patient obtained the medication was statistically significant in predicting adherence. Patients that obtained the medication via the SUS had poorer adherence compared to those that obtained the medication via Health Insurance (coeff.=-0.38 [-0.68;-0.09]; p-value = 0.010) and via Private Health Expenses (coeff.=-0.81 [-1.42;-0.21]; p-value = 0.008). It was also found that considering all three main options available to obtain the medication, 30 patients (68.18%) that obtained the medication via the SUS had already forgotten to take the medication once; whereas only 18 patients (40%) that obtained the medication via Health Insurance had done (Chi-Square = 7.1116; p-value = 0.008). Besides that, it was found that only 22 patients (50%) that obtained the medication via the SUS knew the type of cancer they had. Considering only patients that obtained the medication via Health Insurance, 35 patients (77.78%) knew the type of cancer they had (Chi-Square = 7.4546; p-value = 0.006). Conclusion: The results of this study do not match the literature on the topic, and it could be explained by a poorer doctor-patient relationship at SUS as non-clarification on the importance of adjuvant treatment can be related to a poorer adherence. Citation Format: ANA CRISTINA HERRERA, Caio C. Kasai, Eduarda T. Gonçalves, Liemi A. Homa, Carlos Eduardo E. de Oliveira. Adjuvant Endocrine Therapy adherence in Breast Cancer patients and the Brazilian National Health System [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-58.

Challenges and commonly used countermeasures in the implementation of lifelong antiretroviral therapy for PMTCT in Central Uganda: Health providers' perspective.

Uganda has implemented lifelong antiretroviral therapy for the prevention of mother-to-child HIV transmission since September 2012. Implementation of this strategy has been met with health provider and client challenges which have persisted up to date. This study explored providers' perspectives on the challenges and countermeasures of the implementation and scale-up of lifelong ART among pregnant and breastfeeding women. A qualitative descriptive study was conducted whereby 54 purposively selected participants from six facilities in three districts of Central Uganda namely; Masaka, Mityana, and Luwero were recruited. A key informant interview guide was used to collect data from the study participants. The data were thematically analysed using Atlas-ti, Version 7. Study participants reported challenges under the themes of 1) inadequacy of HIV service delivery (lack of relevant training, health provider shortages, inadequate counselling, stock-outs of essential HIV commodities); 2) Non-utilization of HIV services (Non-disclosure of HIV- positive results, denial of HIV positive results, fear to be followed up, unwillingness to be referred, large catchment area, lack of transport); and 3) Suboptimal treatment adherence (fear of ART side effects, preference for traditional medicines, low male partner involvement in care and treatment). Strategies such as on-job training, mentorship, task shifting, redistribution of HIV commodities across facilities, accompanying of women to mother-baby care points, ongoing counseling of women, peers, and family support groups were commonly used countermeasures. This study highlights key challenges that health providers face in implementing lifelong antiretroviral therapy services among pregnant and postpartum women. Context-specific, innovative, and multilevel system interventions are required at national, district, health facility, community and individual levels to scale up and sustain the lifelong antiretroviral therapy strategy among pregnant and breastfeeding women.

POS1229 THE IMPACT OF COVID-19 ON MEDICATION NON-ADHERENCE IN A RHEUMATOID AND PSORIATIC ARTHRITIS UK COHORT

BackgroundIn March 2020, as part of the UK’s COVID-19 prevention strategy, those identified as ‘clinically extremely vulnerable’, were advised to shield. This included a number of patients prescribed anti-rheumatic drugs, who were asked to continue their current treatment unless they developed symptoms of infection. Suboptimal treatment adherence (16.0%-81.0%) has been reported in patients with arthritic diseases, and is associated with psychological factors, including anxiety (1). Previous literature in non-UK cohorts has highlighted suboptimal adherence levels in immunosuppressed patients during the pandemic, although many were single centre studies (2,3).ObjectivesThe aim of this multi-centre study is to investigate the impact of the COVID-19 pandemic on adherence to anti-rheumatic medications in patients with established rheumatoid (RA) and psoriatic (PsA) arthritis in the UK who had recently commenced a biologic or targeted synthetic DMARD.MethodsBetween September 2020 and May 2021, RA and PsA patients prescribed biologic or targeted synthetic anti-rheumatic drugs from two multi-centre observational studies (BRAGGSS and OUTPASS) were sent a questionnaire on medication usage, adherence, and perceptions to establish the impact of COVID-19 on these parameters. Patients were asked about compliance during the COVID-19 pandemic using a 5-point Likert scale (always, often, sometimes, rarely, and never) and the reason for non-adherence. Adherence was defined as never missing or delaying a dose, unless medically advised. Descriptive summary statistics were calculated, and logistic regression and Pearson’s chi-squared tests were employed to investigate variables associated with self-reported non-adherence.ResultsIn total 159 questionnaires were returned (81.1% RA and 18.9% PsA). Methotrexate (53.5%) was the most frequently prescribed agent, followed by etanercept (25.2%), sulfasalazine (22.6%), hydroxychloroquine (21.4%) and adalimumab (19.5%). Furthermore, 68.6% of patients were prescribed ≥2 drugs. During the pandemic, 42.1% of patients reported missing or delaying a treatment dose for any reason. Adherence information was available for 97.5% of patients with 25.8% reporting non-adherence which was not medically advised. Methotrexate non-adherence was 27.1%, with similar levels reported for etanercept (20.0%), sulfasalazine (27.8%), hydroxychloroquine (35.3%) and adalimumab (29.0%). No drugs had significantly different adherence compared to methotrexate. Furthermore, there was no association between disease type or perception of disease control and adherence. Of non-adherent patients, 17.5% reported increased anxiety, fear, and increased risk due to the COVID-19 pandemic as an influencing factor. Meanwhile, 37.5% of non-adherent patients listed non-COVID-19 intentional reasons and 45.0% reported non-intentional reasons, with forgetting and running out of treatment listed most frequently.ConclusionIn a UK cohort self-reported non-adherence was reported in 25.8% of patients during the COVID-19 pandemic, despite medical advice, with reasons including increased anxiety due to COVID-19.

Forgiveness of INSTI-Containing Regimens at Drug Concentrations Simulating Variable Adherence In Vitro.

ABSTRACTThe integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine (3TC), and DTG/rilpivirine (RPV) are all approved for treatment of HIV-infected patients, with various limitations. Here, time to in vitro viral breakthrough (VB) and resistance barrier using simulated human drug exposures at either full or suboptimal treatment adherence to each regimen were compared. At drug concentrations corresponding to full adherence and 1 missed dose (Cmin and Cmin−1), no VB occurred with any regimen. At Cmin−2, VB occurred only with DTG+3TC, with emergent resistance to both drugs. At Cmin−3, VB occurred with all regimens: 100% of DTG+3TC cultures had VB by day 12, and <15% of BIC+FTC+TAF, DTG+FTC+TAF, and DTG+RPV cultures had VB. Emergent reverse transcriptase (RT) or integrase (IN) resistance was seen with DTG+RPV and DTG+3TC but not with BIC+FTC+TAF or DTG+FTC+TAF. At Cmin−4, 100% VB occurred with DTG+3TC and DTG+FTC+TAF by day 12, while 94% VB occurred with DTG+RPV by day 25 and only 50% VB occurred with BIC+FTC+TAF by day 35. Emergent Cmin−4 drug resistance was seen with all regimens but at differing frequencies; DTG+RPV had the most cultures with resistance. Emergent resistance was consistent with clinical observations. Overall, under high adherence conditions, no in vitro VB or resistance development occurred with these INSTI-based regimens. However, when multiple missed doses were simulated in vitro, BIC+FTC+TAF had the highest forgiveness and barrier to resistance of all tested regimens. Compared to DTG+3TC and DTG+FTC+TAF, DTG+RPV had higher forgiveness but lower resistance barrier after several simulated missed doses.

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016-2019.

Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The "Treat all" strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 -December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30-45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8-51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21-2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51-3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35-44 (aHR 0.65, 95%CI: 0.44-0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39-0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53-3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75-3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57-6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51-0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20-0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects-average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06-1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11-2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01-0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004-0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes.

Treating children with tuberculosis—Using pharmacometrics to do better

Treating children with tuberculosis—Using pharmacometrics to do better

Is the unrealistic expectation of getting cured related to poor treatment adherence among Indian Asthma patients? A hospital based mixed methods study from central India.

ABSTRACTBackground:Prevention of premature deaths due to asthma requires continued disease control through efforts of both patients and healthcare providers. The expectations of patients have been shown to influence treatment adherence and disease control.Methodology:We conducted a hospital-based sequential exploratory mixed methods study and used definitions of the Global Initiative for Prevention of Asthma (GINA). We recruited 80 asthma patients in a tertiary public health facility of central India. We assessed treatment expectations, health literacy, awareness, behavioural risk factors, self-care, treatment adherence, and disease control. We conducted a thematic analysis of qualitative data through manual inductive coding and used statistical software R version-3.6.1 for quantitative analysis.Results:Sixty-seven (83.75%) patients expected that the current doctor would help them achieve ‘cure’, while 28 (35%) expected to obtain information about asthma. 81.2% and 77.5% of participants had inadequate health literacy and inadequate awareness, respectively. 73.8% were using inhalers and 21.2% were not using any treatment. Forced expiratory volume in 1 (FEV1) and Forced vital capacity (FVC) values were available for only 46.25%, while a meagre 6.25% were using peak-flow meter for self-monitoring. Though 21.2% reported optimal treatment adherence, 27.5% had good control. We found the expectation of cure and poor health literacy being significantly related to sub-optimal treatment adherence. We didn’t find any association between the expectations of patients and their disease control.Conclusion:Asthma patients in our setting mostly expected to get cured. The unrealistic expectation of ‘cure’ is related to poor treatment adherence and possibly poor disease control.

888. In Vitro Forgiveness of INSTI-Containing Regimens at Drug Concentrations Simulating Variable Adherence

BackgroundThe integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine (3TC), and DTG/rilpivirine (RPV) are all used for treatment of HIV-infected patients. Here, relative time to in vitro viral breakthrough (VB) and resistance barrier using simulated human drug exposures at either full or suboptimal treatment adherence to each regimen were compared.MethodsWild-type HIV-1 (IIIb)-infected MT-2 cells were exposed to the combinations of BIC+FTC+TAF, DTG+FTC+TAF, DTG+3TC, or DTG+RPV for up to 35 days or until VB. Fixed drug concentrations were the human plasma-free adjusted clinical trough concentrations (Cmin) or fixed at simulated Cmin after missing 1 to 4 consecutive doses (Cmin-1 to -4), with many replicates. Drug resistance was studied by next-generation sequencing at ≥2% frequency.ResultsAt drug concentrations corresponding to full adherence and 1 missed dose (Cmin and Cmin-1), no VB occurred with any regimen (Table). At Cmin-2, only DTG+3TC had VB, with some emergent resistance to both drugs. At Cmin-3, all regimens had VB: by day 12, 100% of DTG+3TC wells had VB; for BIC+FTC+TAF, DTG+FTC+TAF, and DTG+RPV, < 15% of wells had VB which began after day 14. Emergent RT or IN resistance was seen for DTG+RPV and DTG+3TC but not for BIC+FTC+TAF or DTG+FTC+TAF. At Cmin-4, all DTG+3TC and DTG+FTC+TAF wells had VB by day 12, while DTG+RPV had 94% VB by day 25 and BIC+FTC+TAF had 50% VB by day 35. Emergent Cmin-4 drug resistance was seen for all regimens but at differing frequencies; DTG+RPV had the most wells with resistance. Cumulatively, emergent RT and/or IN resistance was found in 1.3% BIC+FTC+TAF, 2.5% DTG+FTC+TAF, 7.9% DTG+3TC, and 8.8% DTG+RPV cultures.Summary of Forgiveness and Barrier to Resistance of INSTI-Containing Regimens ConclusionRegimen forgiveness and resistance barrier are important factors in long term treatment. These INSTI-based regimens had high in vitro forgiveness and resistance barriers with concentrations simulating high adherence. When multiple missed doses were simulated in vitro, BIC+FTC+TAF had the highest forgiveness and barrier to resistance. When compared to DTG+3TC and DTG+FTC+TAF, DTG+RPV had higher forgiveness but lower resistance barrier after several simulated missed doses.Disclosures Rima K. Acosta, BS, Gilead Sciences, Inc. (Employee, Shareholder) Andrew Mulato, BS, MBA, Gilead Sciences, Inc. (Employee, Shareholder) Michelle L. D’Antoni, PhD, Gilead Sciences (Employee, Shareholder)Gilead Sciences, Inc (Employee, Shareholder) Stephen R. Yant, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Tomas Cihlar, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Kirsten L. White, PhD, Gilead Sciences, Inc (Employee, Shareholder)

Demographic and Clinical Factors Are Associated With Frequent Short-Notice Cancellations in Veterans With Multiple Sclerosis on Disease Modifying Therapies

Objectives(1) To identify the rate of short-notice canceled appointments in a large national sample of persons with multiple sclerosis (MS) and (2) examine the demographic and clinical factors associated with frequent cancellations. DesignRetrospective cross-sectional cohort using electronic health records. SettingVeterans Health Administration. ParticipantsVeterans with MS (N=3742) who were part of the Veterans Health Administraiton's MS Center of Excellence Data Repository and (1) had at least one outpatient appointment at the VA in 2013, (2) were alive in 2015, and (3) were prescribed a disease modifying therapy (DMT). InterventionsNot applicable. Main Outcome MeasuresFrequent short-notice cancellations, defined as >20% of scheduled appointments canceled with less than 24-hour notification over a 24-month period. This threshold was based on the definition of ≤80% for suboptimal treatment adherence. Several demographics and clinical variables were examined as potential explanatory factors. ResultsApproximately 75% (n=2827) had at least 1 short-notice cancellation, with more than 3% (n=117) categorized as frequent cancelers. The odds of frequent cancellations were greater in women (odds ratio [OR], 1.81; P=.004) and among 18- to 44-year-olds (OR, 2.77; P=.004) and 45- to 64-year-olds (OR, 2.49; P=.003) compared to those over 65. The odds were lower among persons who lived <25 miles away (OR, 0.58; P=.043) compared with persons who lived ≥75 miles away and those who had at least 1 emergency department visit (OR, 0.55; P=.012). ConclusionsShort-notice cancellations are common in persons with MS, although few have more than 20%. These findings highlight who is at greater risk for frequent cancellation and disruptions in their care. Although additional research is needed, the results provide insights into how clinics may approach handling frequent short-notice cancellations among persons with MS.

Systematic Review: Diabetes Family Conflict in Young People With Type 1 Diabetes.

To investigate the relationships between diabetes-specific family conflict and health outcomes of young people with type 1 diabetes (T1D). A systematic review was performed according to the PRISMA statement (registration number: CRD42020164988). PubMed, Embase, PsycNET, reference lists of included studies, and other relevant reviews were searched (1990-2020). Two independent reviewers screened titles, abstracts, and full-texts. Studies were included if they sampled young people with T1D (mean age between 14 and 25 years) and examined the relationship between diabetes-specific family conflict and the following outcomes: glycated hemoglobin (HbA1c), treatment adherence, blood glucose monitoring, depression, anxiety, quality of life, and/or well-being. A total of 20 studies met the predetermined inclusion criteria. Greater diabetes-specific family conflict was significantly related to higher HbA1c values in 17 studies. Seven studies reported a significant association between greater diabetes family conflict and suboptimal treatment adherence and/or less frequent blood glucose monitoring. However, significant relationships between conflict and HbA1c and/or treatment adherence were not found in four studies. Seven studies in total reported that greater diabetes family conflict was significantly related to poorer quality of life or well-being and greater depressive and/or anxiety symptoms in young people. Diabetes-specific family conflict is associated with some adverse health outcomes for young people with T1D. However, more longitudinal studies of young people aged older than 16 years are needed. Screening for and addressing diabetes-specific family conflict is recommended, given the growing number of studies linking family conflict to various adverse health outcomes in young people with T1D.

Real-world treatment patterns, adherence, costs, and healthcare resource utilization associated with Waldenström macroglobulinemia in the United States.

e18766 Background: Waldenström macroglobulinemia (WM) is a rare, incurable non-Hodgkin lymphoma. Given limited real-world data on WM treatment utilization, this study evaluates real-world treatment patterns and associated outcomes in the US commercially insured population. Methods: A retrospective observational study was conducted using the IBM MarketScan commercial claims and Medicare supplement database. Adults with ≥2 WM diagnoses and ≥1 WM treatment between 2014 and 2019 were identified. Patients included were newly diagnosed, initiating treatment, and enrolled continuously for 6 months before and ≥60 days following the index date, defined as the first date of WM treatment. Treatment regimens were categorized as: rituximab monotherapy, chemotherapy-based (alone or in combination), proteasome inhibitor-based (alone or in combination with rituximab), ibrutinib (alone or in combination with rituximab), and other regimens. Treatment patterns were evaluated by frequency and duration of treatment regimen. Adherence is measured by discontinuation and switching rates. Healthcare resource utilization examined included inpatient, outpatient, and pharmacy visits. Total costs were calculated as sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM). Treatment regimens, costs, and hospitalizations were examined overall, and by line of therapy. Results: A total of 453 patients (mean age: 67 years, 51% male) received 1st-line therapy (mean duration: 246 days); 143 (32%) patients received 2nd-line therapy (mean duration: 231 days), and 24 (5%) received 3rd-line therapy (mean duration: 212 days). The most commonly used treatment regimens by line of therapy are shown in the treatment pattern table. Discontinuation rates were 43.3%, 50.4%, and 45.8%, and the switching rates were 25.4%, 10.5%, 20.8% during 1st, 2nd, and 3rd line of therapy, respectively. The overall hospitalization rate was 20% with an average length of stay (LOS) of 2.3 days. Approximately 17% (LOS: 1.4 days), 20% (LOS: 1.8 days), and 25% (LOS: 7.0 days) of patients had a hospitalization, during 1st, 2nd, and 3rd line of therapy, respectively. Mean total PPPM costs were $26,688 in overall population, and increased by line of therapy (1st: $18,682; 2nd: $19,171; and 3rd: $36,878). Conclusions: There remains a significant clinical and economic burden with suboptimal treatment adherence in US commercially-insured patients with WM. Future studies are needed to further understand factors associated with treatment selection. [Table: see text]

Correlates of missed HIV appointments in low-resource settings: a study from Uganda

Aims: Alarming reports of antiretroviral treatment failure have recently emerged in sub-Saharan Africa. The onset of virologic failure has multiple causes but suboptimal treatment adherence is one of the leading causes. This study aimed to explore correlates of adherence to HIV appointments in community care patients living with HIV/AIDS in Uganda. Methods: Two hundred and ninety-five people living with HIV (median age 37.0 years; interquartile range 16.0; female 67.8% [n = 200]) reported whether they had missed any of their four-weekly appointments during the past 24 weeks. They also completed the Internalized AIDS-Related Stigma Scale, Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9, the Alcohol-Use Disorders Identification Test, and the Physical Activity Vital Sign. Results: Thirty-three (11.2%) patients missed at least one of their six scheduled appointments in the 24-week period. The adjusted odds ratio for missing at least one of six appointments was 3.03 (95% CI: 1.21–8.43, p = 0.01) for those who were physically inactive, and 2.29 (95% CI: 0.93–5.63, p = 0.046) for those with depression. Conclusions: Targeting future rehabilitation studies for PLHIV around feelings of depression and around physical inactivity could be important in achieving optimal HIV treatment adherence.