Treatment Interruption Research Articles

HIV treatment outcomes after 10 years on ART in the TREAT Asia Observational Database (TAHOD) and Australian HIV Observational Database (AHOD).

Increasing numbers of people with HIV have received prolonged antiretroviral therapy (ART). We assessed long-term immunological and survival outcomes among people with HIV from Asia (TAHOD) and Australia (AHOD). People with HIV receiving ART for ≥10 years were included. Factors associated with CD4 counts in years 11-15 of ART were analysed using repeated measure linear regression. Survival after 10 years was analysed using competing risk regression. There were 7139 people included: 4867 (68%) from TAHOD and 2272 (32%) from AHOD. Higher CD4 after 10 years were observed if the nadir CD4 in the first decade was higher (CD4 (cells/µL) 101-200: difference=35, 95%CI 18, 51; >200: difference=125, 95%CI 107, 142) compared to ≤50. The same patterns were observed in those who achieved CD4 ≥500 cells/µL which subsequently decreased to <500 (difference=225, 95%CI 213, 236); or those who achieved and maintained CD4 ≥500 cells/µL (difference=402, 95%CI 384, 420), compared to always <500 in the previous decade. Prior protease inhibitor (PI) -based regimen (difference=-17, 95%CI -33, -1) compared to no PI, and previous treatment interruptions (TI) of 14 days to 3 months and >6 months were associated with lower CD4 counts after 10 years (difference = -38, 95%CI -62, -15; and difference=-44, 95%CI -61, -27, respectively) compared to no TI. The mortality rate was 1.04 per 100 person-years. Virological failure was associated with subsequent mortality (sub-hazard ratio=1.34, 95%CI 1.04, 1.71). Sustaining high CD4 levels and minimising TI has far-reaching benefits well beyond the first decade of ART.

Characteristics and treatment outcomes of patients with multi-drug-resistant tuberculosis at Abbassia Chest Hospital

BackgroundMulti-drug-resistant tuberculosis (MDR-TB) remains a significant health concern. This study analyzes patients admitted to Abbassia Chest Hospital, focusing on their characteristics, drug resistance patterns, treatment outcomes, and risk factors for poor prognosis.MethodsA retrospective cohort study was conducted on 121 patients admitted to the MDR unit at Abbassia Chest Hospital. TB diagnosis was confirmed using sputum smear microscopy, microbiological culture and sensitivity testing, and molecular methods (GeneXpert). Patient data were extracted from hospital records for statistical analysis.ResultsThe mean age of MDR-TB patients was 40 years, with 75.21% being male. Key risk factors included prior TB interrupted treatment, smoking, and contact with MDR-TB patients. Resistance rates exceeded 90% for cycloserine, ethionamide, pyrazinamide, and levofloxacin, while 71.9% were resistant to amoxicillin. Sputum conversion occurred in 95.04% of patients, with a mean conversion time of 2.21 ± 1.44 months. Successful treatment was achieved in 84.3% of cases, while 45.45% experienced side effects, the most common being hyperuricemia (28.1%), gastritis, and ototoxicity (11.57% each). Bad prognosis was associated with comorbidities like ischemic heart disease (OR 15.34, p = 0.02) and delayed sputum conversion (OR 1.63/month, p = 0.03). Side effects were not linked to bad outcomes.ConclusionWhile most MDR-TB patients achieved successful treatment outcomes, certain factors, such as comorbidities (particularly ischemic heart disease) and delayed sputum conversion, significantly contributed to bad prognosis.

Tuberculosis treatment interruption: a qualitative exploration of barriers, challenges, coping strategies and facilitators in Malaysia.

Tuberculosis (TB) treatment interruption undermines the effectiveness of TB medications and jeopardizes treatment outcomes. This study aimed to explore barriers, challenges, coping strategies and facilitators of TB treatment interruption to understand the treatment pathway in achieving successful outcomes. In-depth interviews were conducted at public health clinics in Sarawak, Malaysia, utilizing a phenomenological approach. Thirty patients who experienced TB treatment interruption with eventual successful treatment were purposively selected based on various reasons for treatment interruption to obtain diverse viewpoints. The audio-recorded transcriptions underwent thematic and content analysis. Five major themes emerged under barriers and challenges: socioeconomic, patient, therapy, healthcare and condition-related factors. Notably, financial burdens led individuals to prioritize work over health. Adverse drug reactions resulted in inappropriate self-medication and healthcare dissatisfaction. Medication error with suboptimal dosing was another facet leading to treatment forfeiture. Lack of knowledge about treatment duration and medication adherence, along with negative personal factors such as laziness, dishonesty and forgetfulness were reported. Participants employed coping strategies to confront barriers and challenges, including acceptance and commitment to disease and treatment, self-adaptation in mental, physical and social aspects, and self-management of minor adverse events. Fear of disease worsening, previous experiences, social and financial supports, along with intrinsic motivators, were essential facilitators that prevented interruptions. Interconnectivity across the explored dimensions contextualized the understanding of TB treatment interruption and offered valuable information for designing patient-centered intervention strategies. Improving patient education coupled with tailored interventions addressing psychosocial and economic barriers is crucial for ensuring TB treatment completion.

The heterogeneity among people re-engaging in antiretroviral therapy highlights the need for a differentiated approach: results from a cross-sectional study in Johannesburg, South Africa.

Disengagement and re-engagement with antiretroviral therapy (ART) are common in South Africa, but routine monitoring is insufficient to inform policy development. To address this gap, Anova implemented the 2020 National Adherence Guidelines' re-engagement standard operating procedure (re-engagement SOP) and collected additional data to describe the characteristics of re-engagement visits to inform HIV programmes. Between July and December 2022, we conducted a study at nine primary healthcare facilities in Johannesburg. Staff were trained on the re-engagement SOP and provided with job aides to support implementation. Administration clerks categorized visits based on the time elapsed since the missed appointment: ≤14days and >14 days, with the latter identified as re-engaging. For these clients, clinicians filled out "re-engagement clinical assessment forms" that included visit dates, both clinician-assessed and self-reported treatment interruptions, and clinical details. Data on missed appointments and previous viral loads were extracted from medical records. The information was entered into REDCap. We present data from three out of the nine facilities, selected for their comprehensive data collection and high coverage of all re-engaging clients. A total of 2342 clients returned following a missed scheduled appointment. The majority, 1523 (65%), missed their appointments by ≤ 14 days, while 819 (35%) were >14 days late (re-engaging). Among those re-engaging, 635 (78%) re-engagement clinical assessment forms were completed. A missed appointment date was available for 623 with 25% (n = 161) returning 2-4 weeks late, 47% (n = 298) 4-12 weeks and 26% (n = 164) >12 weeks late. Self-reported ART interruption, available for 89% (567/635), indicated the majority (54%, n = 304) experienced no interruption. Clinical concerns were identified in 65 (10%) cases. A majority (79%, 504/635) had prior viral load results, with 73% (370/504) below 50 copies/ml. Clients frequently return to care shortly after missed appointments. Despite missing scheduled ART refill dates, many report not interrupting treatment, either having treatment on hand or sourcing ART elsewhere. Most re-engaging clients were adherent prior to disengagement, and clinical concerns are rare. A differentiated service delivery approach, prioritizing flexibility and reduced healthcare burden, is required to support client's needs and preferences at re-engagement.

Mathematical modeling framework enhances clinical trial design for maintenance treatment in oncology

Clinical trials are costly and time-intensive endeavors, with a high rate of drug candidate failures. Moreover, the standard approaches often evaluate drugs under a limited number of protocols. In oncology, where multiple treatment protocols can yield divergent outcomes, addressing this issue is crucial. Here, we present a computational framework that simulates clinical trials through a combination of mathematical and statistical models. This approach offers a means to explore diverse treatment protocols efficiently and identify optimal strategies for oncological drug administration. We developed a computational framework with a stochastic mathematical model as its core, capable of simulating virtual clinical trials closely recapitulating the clinical scenarios. Testing our framework on the landmark SOLO-1 clinical trial investigating Poly-ADP-Ribose Polymerase maintenance treatment in high-grade serous ovarian cancer, we demonstrate that managing toxicity through treatment interruptions or dose reductions does not compromise treatment’s clinical benefits. Additionally, we provide evidence suggesting that further reduction of hematological toxicity could significantly improve the clinical outcomes. The value of this computational framework lies in its ability to expedite the exploration of new treatment protocols, delivering critical insights pivotal to shaping the landscape of upcoming clinical trials.

Real-World Experience of Imipenem-Relebactam Treatment as Salvage Therapy in Difficult-to-Treat Pseudomonas aeruginosa Infections (IMRECOR Study).

Difficult-to-treat-resistant (DTR) infections caused by Pseudomonas aeruginosa represent a global public health threat, prioritizing the search and development of new antibiotics for this microorganism. We present the real-life experience of the compassionate use of imipenem/cilastatin/relebactam in a descriptive study involving 14 patients with DTR-P. aeruginosa infection and limited treatment options. The primary source of infection was skin and soft tissue infection, 57.1% (8/14), followed by respiratory infection-pneumonia, 28.6% (4/14). At the onset of infection, 71.4% (10/14) of patients were in the intensive care unit (ICU). All our patients had a Charlson Score of ≥ 3. Septic shock was observed in 64.3% (9/14) of patients. The median treatment duration was 15days, and no patient experienced an adverse event that required treatment interruption. All-cause 30-day mortality was observed in 42.9% of cases (6/14), while clinical efficacy and microbiological success were observed in 64.3% (9/14). Imipenem/cilastatin/relebactam may represent a treatment option for patients with DTR-P. aeruginosa infections, which should be validated in prospective clinical trials.

Efficacy and safety of bendamustine, rituximab and bortezomib treatment in relapsed/refractory Waldenstrom Macroglobulinaemia: results of phase 2 single-arm FIL-BRB trial.

This multicentre phase II study Fondazione Italiana Linfomi (FIL)-bortezomib plus rituximab plus bendamustine (BRB) tested a combination of bendamustine (90 mg/m2 on days 1-2), rituximab (375 mg/m2 intravenously on day 1) and bortezomib (1.3 mg/m2 sc on days 1, 8, 15, 22) every 28 days for six cycles in 38 symptomatic patients with relapsed/refractory Waldenstrom macroglobulinaemia (RR-WM). Moreover, MYD88L265P and CXCR4S338X mutations were tested by droplet digital polymerase chain reaction (ddPCR) both at baseline and at the end of treatment in 21 patients. Overall response rate at the end of therapy was 84.6%, including 4 (11%) complete remission, 15 (39%) very good partial response, 12 (32%) partial responses according to IWWM response criteria. At 18, 24 and 30 months, progression-free survival was 84.2% (95% CI 68.2%-92.6%), 81.5% (95%CI 65.1-90.7) and 78.8% (95%CI 62.0-88.8) respectively. At 18 months, the Overall survival was 92.1% (95%CI 77.5%-97.4%). Overall, 19 patients (50%) experienced grade 3-4 haematological toxicity, mainly thrombocytopenia, and grade 1-3 neuropathy rate was about 10% and required bortezomib dose reduction but did not result in treatment interruption. Moreover, BRB treatment induced the high rates of undetectable molecular minimal residual disease (MRD) at the end of the therapy. BRB regimen used as second line is an effective and well-tolerated salvage treatment for relapsed refractory Waldenstrom macroglobulinaemia patients. MRD monitoring showed promising efficacy in clearing the residual disease.

Impact of Fingolimod Discontinuation Strategy on Recurrence of Disease Activity in Individuals With Multiple Sclerosis.

For individuals with multiple sclerosis (MS), treatment interruption can result in relapse/recurrence of the disease activity. Currently, there are no consensus guidelines about whether an abrupt stop with a short washout period or gradual tapering is better for fingolimod (Gilenya) cessation. We investigated the impact of the fingolimod discontinuation strategy on the recurrence of disease activity and the rebound occurrence of symptoms during washout. This was a retrospective, observational, multicenter study of individuals with MS in Egypt and Kuwait. The charts of patients on fingolimod therapy were screened to collect data on the impact of drug cessation strategies on disease activity and relapse occurrence. Disease relapse after cessation was defined as a relapse that occurred in the previous 12 months despite using a first-line treatment option or 2 relapses in the previous 12 months. In a cohort of 100 patients, 58 had an abrupt cessation and 42 had a gradual tapering. Compared with abrupt cessation, gradual tapering was associated with a significantly lower rate of disease relapse (4.8% vs 81%, respectively; P = .001). Abrupt cessation also resulted in increased MRI findings of new lesions (24.1%; P = .29), enhancing lesions (32.8%; P = .5), and enlarging lesions (6.9%; P = .59); however, none of the MRI findings were significant. Other risk factors showed no significant association with disease relapse after fingolimod cessation. Gradual fingolimod tapering is highly recommended to decrease the risk of rebound and severe disease reactivation. A prolonged washout should be avoided for lymphocyte recovery.

Top-down infliximab plus azathioprine versus azathioprine alone in patients with acute severe ulcerative colitis responsive to intravenous steroids: a parallel, open-label randomised controlled trial, the ACTIVE trial

BackgroundIt is unknown which maintenance therapy is the most effective option for patients admitted for an acute severe ulcerative colitis (ASUC) episode responding to intravenous steroids.MethodsWe conducted a multicentre, parallel-group, open-label randomised controlled trial among 23 French centres in thiopurine and biologics-naïve adults admitted for ASUC responding to intravenous steroids. Eligible patients were randomly assigned to receive infliximab (IFX) and azathioprine (AZA) with a 7-day steroid tapering scheme (IFX+AZA arm) or AZA and conventional standardised steroid tapering regimen (AZA arm). The primary composite endpoint was treatment failure at week 52, defined as the absence of steroid-free clinical remission, the absence of endoscopic response, the use of a prohibited treatment for relapse, severe adverse event leading to treatment interruption, colectomy or death. Multiple imputation for missing data was performed.FindingsAmong the 64 patients randomised (Lichtiger score 13.5±2.0; median age of 34.5 (P25–P75 26.3–50.3) years, median C reactive protein of 29.0 (12.8–96.8) mg/L at baseline): 32 were assigned to the IFX+AZA arm and 32 to the AZA arm. In the ITT population, treatment failure at week 52 was observed in 22/27 (81.5%) in the AZA arm and 16/30 (53.3%) in the IFX+AZA arm (risk ratio 3.85, 95% CI (1.15 to 12.88), p=0.03). 29 adverse events were severe, including 13 disease exacerbations, 6 severe infections without any difference between both arms.InterpretationCombination therapy with IFX+AZA was more effective at 1 year than AZA alone to avoid treatment failure in patients with ASUC responding to intravenous steroids.Trial registration numberNCT02425852.

Management of severe immune-related adverse events and outcomes in patients with advanced non-small cell lung cancer receiving immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) are associated with severe immune-related adverse events (s-irAEs) that result in hospitalization, emergency department (ED) visits, treatment discontinuation, or death. This study examined the impact of s-irAEs and their earliest management strategies on clinical outcomes in advanced non-small cell lung cancer (NSCLC). Data were derived from ConcertAI Patient360 NSCLC, a US-based electronic medical record database, between January 2012 and May 2021. Eligible patients had advanced NSCLC and received ICI-containing therapy. s-irAEs and management actions were abstracted from unstructured EHR data from ICI initiation through the earliest of 100 days after ICI discontinuation, start of a non-ICI-containing regimen, loss to follow up, end of study period, or death. Multivariable Cox regression analysis was used to evaluate the association between s-irAEs and their earliest management strategies, and real-world progression-free survival (rwPFS) and real-world overall survival (rwOS). The study included 3211 patients. Median (IQR) age was 67 (60-73) years, and 44.9% were female. Most patients (61.6%) initiated ICIs as first-line therapy; half (50.1%) initiated ICIs as monotherapy, with nivolumab monotherapy (29.5%) as the most common initial ICI-containing regimen in any line. Overall, 8.6% of patients experienced s-irAEs, most often diarrhea (3.5%), pneumonitis (1.4%), and rash (1.3%). Among patients who experienced at least one s-irAEs, over half (57.4%) were hospitalized, and 71.8% were treated with corticosteroids, any time after the occurrence of their first s-irAEs. Median rwPFS was 4.9 (95%CI, 4.6-5.2) months, and median rwOS was 13.6 (12.6-14.7) months from ICI initiation. rwPFS and rwOS were comparable between patients with s-irAEs vs patients without s-irAEs when s-irAEs were first managed with anti-cancer treatment interruptions. Patients with s-irAEs had a 53% (22.3%-91.4%) higher risk of death than patients without s-irAEs when s-irAEs initially required corticosteroids or other immunosuppressants, and a 61% (37.9%-87.9%) higher risk of death when s-irAEs first required hospitalization or ED admission. The impact of s-irAEs on clinical outcomes may depend on the initial intervention required to manage the adverse event. s-irAEs were associated with worse outcomes when they initially required hospital/ED admission, corticosteroids, or other immunosuppression.

Bimekizumab Efficacy and Safety Over 48 Weeks in US and Canadian Patients with Psoriasis who had a Treatment Interruption After 3 Years of Treatment: Results from BE RADIANT

Bimekizumab Efficacy and Safety Over 48 Weeks in US and Canadian Patients with Psoriasis who had a Treatment Interruption After 3 Years of Treatment: Results from BE RADIANT

Enteral tube administration of extemporaneously compounded suspensions of venetoclax according to an institutional medication use process.

Venetoclax is a potent oral oncology drug (OOD) frequently used to treat hematologic cancers due to its convenience and high efficacy. However, some patients cannot tolerate solid oral formulations, requiring a reformulated version of venetoclax for effective administration. Currently, there is limited information in the literature regarding the extemporaneous compounding of venetoclax. We present our institution's medication use process (MUP) for preparing compounded suspensions of venetoclax for patients with dysphagia who cannot tolerate solid oral formulations. This report has two main aims: to review our MUP from design to implementation, illustrated with real patient cases, and to present it as a strategy for administering venetoclax-based therapies to patients with dysphagia or feeding tubes. From February 2020 to January 2024, 17 patients received venetoclax through the standard MUP, with four developing tumor lysis syndrome (TLS). This study describes their clinical courses and evaluates their responses to the compounded suspensions, considering the uncertain effects of venetoclax prepared through this method. The four patients received venetoclax suspensions during hospitalization due to swallowing difficulties or nutritional support needs. We prepared extemporaneous venetoclax suspensions to ensure continuous therapy, thus avoiding treatment interruptions. TLS was managed using rasburicase and prophylactic allopurinol. The clinical outcomes indicate that the current MUP provides a practical approach to administering venetoclax for dysphagic patients. However, additional research is needed to determine if there are pharmacokinetic differences in the bioavailability of venetoclax between oral and enterally delivered formulations. Further studies will help inform best practices for patient care.

Financial toxicity in patients with chronic kidney disease undergoing peritoneal dialysis

Abstract Objective: To investigate financial toxicity (FT) and the factors influencing it in patients with chronic kidney disease undergoing peritoneal dialysis (PD). Methods: A cross-sectional design was used. From August 2023 to December 2023, 148 PD patients were selected for investigation. The selection was conducted using the convenience sampling method across Shenzhen Third People’s Hospital, Peking University Shenzhen Hospital, and The First Affiliated Hospital of Guangzhou University of Chinese Medicine. Patients’ financial toxicity was assessed using a general demographic questionnaire, laboratory test results, and the Comprehensive Score for financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT). T-tests, ANOVA, Pearson’s chi-squared test and multiple linear regression analysis were used to evaluate the predictors of FT in patients with PD. Results: Seventy-nine patients (53.38%) had mild FT, and 61 patients (41.21%) had moderate FT. Age, working status, monthly household income per capita, and PD-related complications were significantly associated with FT in PD patients (P &lt; 0.05). Conclusions: There were varying degrees of FT in PD patients. Measuring FT can help medical professionals develop treatment care strategies, reduce the financial burden on patients, and avoid treatment interruption.

Efficacy and Safety Analysis in Chinese Patients with Moderate-to-Severe Psoriasis from a Phase 3 Trial: Impact of Treatment Withdrawal and Retreatment of Ixekizumab.

In China, approximately 2.3 million people have psoriasis. Continuous treatment is recommended for moderate-to-severe psoriasis. This study aimed to evaluate the outcomes of continuous versus interrupted ixekizumab (IXE) treatment and retreatment with IXE after disease worsening in Chinese patients. In this Phase 3, multicenter, randomized, double-blind, placebo-controlled study, patients were randomized to IXE or placebo at Week 0. At Week 12, IXE responders (static Physician's Global Assessment [sPGA] score, 0 or 1 [0,1]) were re-randomized (2:1) to IXE (IXE/IXE, continuous treatment) or placebo (IXE/PBO, interrupted treatment). After re-randomization, treatment in IXE/PBO patients with disease worsening (relapse, sPGA ≥ 3) was switched to IXE every 4weeks (IXE/PBO + IXEQ4W, retreatment). Efficacy was assessed by evaluating the response rates of Psoriasis Area and Severity Index (PASI) 75/90/100, sPGA (0,1), Dermatology Life Quality Index (DLQI) (0,1), mean PASI, and Itch Numerical Rating Scale (NRS) scores and improvements of special body areas. Safety was evaluated by assessing treatment-emergent adverse events (AEs) and serious AEs. At Week 12, 289 IXE responders were re-randomized to the IXE/IXE group (192 patients) and IXE/PBO group (97 patients). High rates of PASI 75 and sPGA (0, 1) responses were maintained in the IXE/IXE group until Week 60. At Week 60, 88 (90.7%) patients in the IXE/PBO group had disease relapse; the median time to relapse was approximately 20weeks. After 24weeks of retreatment, PASI 75 and sPGA (0, 1) were recaptured (97.2% and 74.6%, respectively, in the IXE/PBO + IXEQ4W group). AEs were comparable in patients who received continuous treatment and retreatment. In Chinese patients who received continuous IXE treatment, high response rates were maintained through 60weeks. Most patients had disease relapse after treatment withdrawal. After retreatment, most of these patients had regained and maintained response since Week 12. NCT03364309.

CTNI-11. A PHASE 1 OPEN-LABEL STUDY OF BRAF INHIBITOR ABM-1310 IN PATIENTS (PTS) WITH RECURRENT BRAF V600-MUTATED PRIMARY CNS TUMORS

Abstract BACKGROUND ABM-1310 is a blood-brain barrier penetrant BRAF inhibitor. Here we report interim results from our phase 1 study of ABM-1310. METHODS This is a dose-escalation plus expansions trial for adult pts with BRAF V600-mutated primary CNS tumors. In the dose-escalation, ABM-1310 is given at 150 or 200 mg twice a day (bid). In the expansion, ABM-1310 150 mg bid is administered. Study objectives include patient safety, maximum tolerated dose (MTD), preliminary efficacy and pharmacokinetics (PK). Clinical trial information: NCT05892653. RESULTS By May 6, 2024, 15 pts (7 male; median age 39 years old) have been treated. In the dose escalation: 4 pts received ABM-1310 150 mg bid, and another 7-pts received ABM-1310 200 mg bid. In the expansion, all 4 pts were given ABM-1310 at 150 mg bid. Among 14 efficacy evaluable pts, 3 had partial response (PR) (including one each of glioblastoma, WHO grade 2 and 3 pleomorphic xanthoastrocytoma) and 9 pts had stable disease as their best responses. Two pts have PR response for &amp;gt; 8 months and continue study treatment. All pts experienced treatment-related AEs. Common AEs were asymptomatic QT prolongation (n=11) and rash (n=10). Seven pts had grade 3 QT prolongation. There was no drug-related SAE. There was no ABM-1310 related dose limiting toxicity although a few pts had study treatment interruption or dose reduction. One patient discontinued prematurely due to asymptomatic Grade 3 QT prolongation. There were no drug-related deaths. The MTD for ABM-1310 was 200 mg bid, the recommended dose was 150 mg bid. In PK assessment, ABM-1310 drug exposure vs. dosage showed a linear proportional relationship. This trial is ongoing. CONCLUSIONS ABM-1310 was generally safe and tolerated. There were no new safety signals. Preliminary efficacy data demonstrate favorable anti-cancer activity in patients with recurrent BRAF V600-mutated primary CNS tumors.

INNV-38. 3 DAYS-ON-1 DAY-OFF FRACTIONATED USE PROTOCOL FOR IMPROVED COMPLIANCE AND PREVENTATIVE SKIN SAFETY FOR USE OF TUMOR TREATING FIELDS: PRACTICE IMPROVEMENT STRATEGY IN NEURO-ONCOLOGY

Abstract BACKGROUND Compassionate care delivery requires that providers understand patient values and adopt practices aimed to improve the quality of extended survival. Many brain tumor clinical trials measure survival outcomes based on therapeutic interventions, but often fail to anticipate patient noncompliance and the provider’s ability to communicate the plan. Tumor Treating Fields (TTFields) is an FDA-approved locoregional, noninvasive therapy worn on the scalp to treat glioblastoma (GBM). When worn, TTFields therapy disrupts cancer cell viability and delays tumor progression but is complicated by mild-moderate skin irritation and real-world inconvenience of the unclear recommendation to wear the device an average of “≥18 hours/day or 75% of the time”. We simplified the physician instructions to encourage patient compliance and skin safety on TTFields. METHODS Adults with GBM were provided an easy-to-follow flow chart and advised across multiple centers to follow the 3-days-on (72 hours) and 1-day-off (16–24 hours) TTFields therapy use schedule and given skin-specific wound prevention guidance (cleansing selenium-based shampoo and reparative skin-barrier moisturizing) during the ‘off day’. We evaluated the ease to explain the 3-on-1-off schedule, patient adherence, and the presence and severity of skin AEs during follow-up visits. REAL-WORLD PRACTICE OUTCOMES Seventy-six patients received TTFields therapy using the 3-on-1-off protocol between 2015 and 2021 at two US healthcare centers. The median age was 57 years (range 25–81). The mean time on TTFields therapy was 73 weeks. Skin AEs occurred in 5% of patients on the 3-on-1-off protocol, as compared to 16% and 52% reported on EF-11 (NCT00379470) and EF-14 (NCT00916409) GBM studies, respectively. Majority of AEs were mild, and no patients discontinued TTFields therapy or modified electrode placement due to skin AEs while on the 3-on-1-off protocol. CONCLUSION We report real-world data confirming a practice improvement for patient compliance using a novel 3-on-1-off protocol which minimizes skin AEs and treatment interruptions to improves patient outcomes. An ounce of prevention is worth a pound of cure.

Multicentric study of adherence to antiseizure medications among adults with epilepsy attended in neurology departments in Burkina Faso.

To study the adherence of antiseizures medication in neurology in the city of Ouagadougou. We conducted a multicentric cross-sectional study on adherence to antiseizure medications among adult patients with epilepsy followed by outpatient neurology consultations. The patients were recruited from November 22, 2021 to February 22, 2022 in four departments of neurology. Adherence to antiseizure medications (ASM) was measured using the Morisky Medication Adhesion Scale (MMAS). Logistic regression analysis was used to investigate factors associated with adherence. One hundred and seven patients with a mean age of 38.92 ± 16.06 years were included in the study. Most of the patients were men (52.34%). Twenty-eight patients complied well with ASM (26.17%). The main causes of nonadherence to treatment were forgetfulness and lack of financial means. Factors associated with nonadherence were rural residence (p = 0.023), celibacy or divorce (p = 0.002), low level of education (p = 0.028), perception of stigma (p = 0.026), duration of epilepsy <5 years (p = 0.009). Adherence to ASM is low in Burkina Faso. The main causes of nonadherence were forgetting and insufficiency of financial resources. Rural residence, celibacy, or divorce, low level of education, perception of stigmatization, and short duration of epilepsy were associated with non-adherence. Studies on adherence to antiseizure medications are rare in Africa while patients do not have access to adequate treatment. The aim of our study was to evaluate the adherence to antiseizure medications among patients with epilepsy followed by the neurology departments in the city of Ouagadougou. Forgetfulness and financial insufficiency were the main causes of treatment interruption. Our study showed that most of the patients were non adherent. Several factors such as place of residence, level of education, and duration of epilepsy influence the level of compliance.

Transient biopsy-proven progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome (PML-IRIS) in an elderly woman without known immunodeficiency: a case report

BackgroundProgressive multifocal leukoencephalopathy (PML) is a severe opportunistic brain disease caused by lytic JC polyomavirus (JCPyV) replication in oligodendrocytes. Although JCPyV infection is common in the general population, PML almost exclusively occurs in patients immunocompromised due to untreated HIV/AIDS, haematological malignancies, primary immunodeficiencies, solid organ transplantation, or immunomodulatory treatment of autoimmune diseases. There is no effective antiviral treatment, and recovery depends on immune reconstitution. Paradoxically, initiation of antiretroviral therapy for HIV/AIDS or interruption of immunomodulating treatment can worsen the clinical manifestations due to immune reconstitution inflammatory syndrome (IRIS). Here, we report an unusual case of spontaneous IRIS in a 76-year-old immunocompetent woman, unmasking PML and leading to unexpected recovery.Case presentationThe patient was admitted to the hospital due to psychosis, speech impairment, and behavioral changes over the last three months. She had previously been healthy, except for a cerebellar stroke secondary to paroxysmal atrial fibrillation. Magnetic resonance imaging (MRI) revealed multiple contrast-enhancing white matter lesions suspicious of cancer metastases. Due to suspicion of edema, dexamethasone was administered, and the patient was released while waiting for a stereotactic brain biopsy. Eight days later, she suffered tonic seizures and was readmitted. Intravenous levetiracetam gave rapid effect, but the patient was paranoid and non-cooperative, and dexamethasone was unintentionally discontinued. Ten days later, the brain biopsy revealed demyelination, abundant perivascular T cells, macrophages, and scattered JCPyV-infected oligodendrocytes, rendering the diagnosis of PML-IRIS. The cerebrospinal fluid contained low amounts of JCPyV-DNA, and plasma contained high levels of anti-JCPyV immunoglobulin G. Despite extensive immunological testing, no evidence of immunodeficiency was found. The patient gradually recovered clinically and radiologically. More than 19 months after diagnosis, the patient has only a slight impairment in language and behavior.ConclusionsAn apparently immunocompetent elderly person developed clinically symptomatic PML, which spontaneously resolved with symptoms and signs of IRIS. The atypical MRI lesions with contrast enhancement and the lack of known immunological risk factors for PML delayed the diagnosis, eventually proved by biopsy. PML and PML-IRIS should be considered in the differential diagnosis of patients presenting CNS symptoms and focal lesions with contrast enhancement on MRI.

Early Viral Dynamics Predict HIV Post-Treatment Control After Analytic Treatment Interruption.

A key research priority for developing an HIV cure strategy is to define the viral dynamics and biomarkers associated with sustained post-treatment control. The ability to predict the likelihood of sustained post-treatment control or non-control could minimize the time off antiretroviral therapy (ART) for those destined to not control and anticipate longer periods off ART for those destined to control. Mathematical modeling and machine learning were used to characterize virologic predictors of long-term virologic control using viral kinetics data from several studies in which participants interrupted ART. Predictors of post-ART outcomes were characterized using data accumulated from the time of treatment interruption, replicating real-time data collection in a clinical study, and classifying outcomes as either post-treatment control (plasma viremia ≤400 copies/mL at 2 of 3 time points for ≥24 weeks) or non-control. Potential predictors of virologic control were the time to rebound, the rate of initial rebound, and the peak plasma viremia. We found that people destined to be non-controllers could be identified within 3 weeks of rebound (prediction scores: accuracy, 80%; sensitivity, 82%; specificity, 71%). Given the widespread use of analytic treatment interruption in cure-related trials, these predictors may be useful to increase the safety of analytic treatment interruption through the early identification of people who are unlikely to become post-treatment controllers.

The burden of HIV-1 and HIV-2 epidemics in Ivory Coast.

Simian immunodeficiency viruses (SIV) infecting chimpanzees (SIVcpz) and sooty mangabeys (SIVsm) are, respectively, the biological precursors of human immunodeficiency viruses (HIV) Types 1 and 2. Former French colonies in West Africa are the regions where retroviruses first jumped from primates to humans. Ivory Coast is nowadays a country of over 29 million people, being 2% (580,000) persons living with HIV (PLWH). However, one-quarter remains undiagnosed. Heterosexual transmission is by far the most frequent mechanism of HIV acquisition and women exhibit higher rates of infection than men. Despite preventive measures, HIV infection in children throughout breastfeeding remains significant. The proportion of PLWH carrying HIV-1 is rising whereas conversely HIV-2 carriers are steadily declining. A nationwide survey conducted on earlier 2024 showed that a total of 188,880 PLWH were on follow-up. HIV-1 infection was found in 163,947, HIV-2 in 5,114, and coinfection in 3,182. HIV type was not reported for 7,500. Antiretroviral therapy with tenofovir, lamivudine, and dolutegravir is by far the most frequently prescribed regimen in Ivory Coast (n = 168,543). Viral suppression is recognized in 94.3% of treated PLWH, despite one-third acknowledging unwanted treatment interruptions after failure of stock supplies. Given shared transmission routes with HIV, coinfection with other human retroviruses such as Human T-lymphotropic virus type-1 (HTLV-1) and/or hepatitis viruses B, C, and delta are frequent in Ivory Coast. Coinfections remain largely undiagnosed and poorly managed. In summary, the HIV pandemic caused by both HIV-1 and HIV-2 is a major public health challenge in Ivory Coast, where strategies for expanding diagnosis, sustain antiretroviral treatment, and manage coinfections warrant further efforts.