Modelling trends of CD4 counts for patients on antiretroviral therapy (ART): a comprehensive health care clinic in Nairobi, Kenya

Background In resource-limited settings, changes in CD4 counts constitute an important component in patient monitoring and evaluation of treatment response as these patients do not have access to routine viral load testing. In this study, we quantified trends on CD4 counts in patients on highly active antiretroviral therapy (HAART) in a comprehensive health care clinic in Kenya between 2011 and 2017. We evaluated the rate of change in CD4 cell count in response to antiretroviral treatment. We further assessed factors that influenced time to treatment change focusing on baseline characteristics of the patients and different initial drug regimens used. This was a retrospective study involving 432 naïve HIV patients that had at least two CD4 count measurements for the period. The relationship between CD4 cell count and time was modeled using a semi parametric mixed effects model while the Cox proportional hazards model was used to assess factors associated with the first regimen change. Results Majority of the patients were females and the average CD4 count at start of treatment was 362.1 $$cell/mm^3$$ c e l l / m m 3 . The CD4 count measurements increased nonlinearly over time and these trends were similar regardless of the treatment regimen administered to the patients. The change of logarithm CD4 cell count rises fast for in the first 450 days of antiretroviral initiation. The average time to first regimen change was 2142 days. Tenoforvir (TDF) based regimens had a lower drug substitution(aHR 0.2682, 95% CI:0.08263- 0.8706) compared to Zidovudine(AZT). Conclusion The backbone used was found to be associated with regimen changes among the patients with fewer switches being observed, with the use of TDF when compared to AZT. There was however no significant difference between TDF and AZT in terms of the rate of change in logarithm CD4 count over time.

192. Tolerability Outcomes of Multi-drug Antibiotic Treatment for Pulmonary Nontuberculous Mycobacterial Disease due to Mycobacterium avium Complex in U.S. Medicare Beneficiaries with Bronchiectasis

Background Nontuberculous mycobacteria (NTM), most frequently Mycobacterium avium complex (MAC), cause increasingly common pulmonary infections. Treatment interruptions and early discontinuation are common in MAC therapy, but population-based data on treatment outcomes are severely lacking. We examined tolerability outcomes of guideline-based 3-drug therapies (GBT) targeted for pulmonary MAC infection. Methods Among beneficiaries with bronchiectasis (ICD-9-CM 494.0 or 494.1) in U.S. Medicare data (01/2006 – 12/2014), we identified first-time MAC GBT therapy users, excluding those with cystic fibrosis, HIV, or a history of organ transplant. MAC GBT was defined as an overlapping prescription of ≥ 28-day supply of a macrolide, ethambutol and rifamycin. Using Cox regression methods, we compared time-to-regimen change or discontinuation within 12 months of therapy start in the following groups: 1) azithromycin-ethambutol-rifamycin vs. clarithromycin-ethambutol-rifamycin; 2) macrolide-ethambutol-rifampin vs. macrolide-ethambutol-rifabutin; and 3) azithromycin-ethambutol-rifampin vs. clarithromycin-ethambutol-rifabutin. Results We identified 4,626 GBT therapy users (mean 77.9 years [s.d. 6.1], female [77.7%], and non-Hispanic white [87.2%]). Overall, the rate of regimen change or discontinuation was higher in the clarithromycin-based regimens compared to azithromycin-containing regimens, and in rifabutin-containing regimens compared to rifampin-containing regimens. The rate of drug regimen change or discontinuation was 65% greater in the clarithromycin-ethambutol-rifabutin group compared to the azithromycin-ethambutol-rifampin group (adjusted hazard ratio: 1.64, 95% CI: 1.43, 1.64) (Table 1, Figure 1). Conclusion Azithromycin-based regimens and rifampin-containing regimens were less likely to be changed or discontinued within 12 months of therapy compared to clarithromycin-based regimens and rifabutin-containing regimens, respectively. More research is needed to identify factors associated with early treatment change or discontinuation. Disclosures Emily Henkle, PhD, MPH, AN2 (Consultant, Advisor or Review Panel member)Zambon (Advisor or Review Panel member) Theodore K. Marras, MD, Astra Zeneca (Speaker’s Bureau)Insmed (Scientific Research Study Investigator)Novartis (Speaker’s Bureau)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Grant/Research Support)Paratek (Consultant)RedHill (Consultant)Spero (Consultant) Kevin L. Winthrop, MD, MPH, Insmed (Consultant, Research Grant or Support)Paratek (Consultant)RedHill Biopharma (Consultant)Spero (Consultant)

Determinants and Reasons for Switching Anti-Retroviral Regimen Among HIV-Infected Youth in a Large Township of South Africa (2002-2019)

Background: There are limited data exploring antiretroviral therapy(ART) changes and time to change among South Africa young people living with HIV/AIDS. Objective: We describe the time to first drug switch, which includes ART regimen change (three drug switch) and substitutions (single drug switch). We describe common reasons for ART switch among young people aged 10 to 24 years in South Africa.Methods: We conducted a retrospective cohort study at a primary health care clinic in Cape Town, South Africa, providing ART to HIV-infected adolescents and adults since 2002. those aged 10 to 24 years at ART initiation, who accessed care clinic between September 2002 and April 2019. Data was retrieved from electronic information systems: ART regimens, ART changes, dates for initiation or stop of each drug/regimen, laboratory results (viral loads, haemoglobin, liver enzyme results, and creatinine to support the reason for ART switch. From written records, we abstracted reason for single drug switch or regimen change, as well as socio demographic and clinical data. We fitted cox regression models to determine factors associated with ART switch and the rate of occurrence. Results: Of 2601 adolescents included, 605 (24.9%) adolescents switched ART over 5090.5 person years at risk (PYAR), a rate of 11.9 /100PYAR. Median follow-up time was 4.4 (±3.2) years. At multivariable analysis, ART switch was independently associated with age 18-24 years, versus 10-17 years: adjusted Hazard Ratio [aHR] 0.78, 95% CI 0.62-0.98, transfer status [transferred out 1.42 [1.11-1.82]. The hazard of ART switch increased with more severe HIV-disease at ART start, as observed by increasing WHO clinical stage or reduced CD4 count at baseline. The primary reasons for ART switch were side effects (20.0%), virological failure (17.9%) and formulation switch (27.8%). Others reasons included pregnancy, Hepatitis B, tuberculosis and psychosis.Conclusion: ART switches are frequent and occur at a consistent rate across 7.5 years from initiation. The main reasons for ART switch were virological failure and drug side effects.

Changes in Home Blood Pressure Monitored Among Elderly Patients With Hypertension During the COVID-19 Outbreak: A Longitudinal Study in China Leveraging a Smartphone-Based Application

Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted clinical care worldwide. Evidence of how this health crisis affected common conditions like blood pressure (BP) control is uncertain. Methods: We used longitudinal BP data from an ongoing randomized clinical trial to examine variations in home BP monitored via a smartphone-based application (app) in a total of 7394 elderly patients with hypertension aged 60 to 80 years stratified by their location in Wuhan (n=283) compared with other provinces of China (n=7111). Change in morning systolic BP (SBP) was analyzed for 5 30-day phases during the pandemic, including preepidemic (October 21 to November 20, 2019), incubation (November 21 to December 20, 2019), developing (December 21, 2019 to January 20, 2020), outbreak (January 21 to February 20, 2020), and plateau (February 21 to March 21, 2020). Results: Compared with non-Wuhan areas of China, average morning SBP (adjusted for age, sex, body mass index) in Wuhan patients was significantly higher during the epidemic growth phases, which returned to normal at the plateau. Between-group differences in ΔSBP were +2.5, +3.0, and +2.1 mm Hg at the incubation, developing, and outbreak phases of COVID-19 ( P <0.001), respectively. Sensitivity analysis showed a similar trend in trajectory pattern of SBP in both the intensive and standard BP control groups of the trial. Patients in Wuhan also had an increased regimen change in antihypertensive drugs during the outbreak compared with non-Wuhan patients. Expectedly, Wuhan patients were more likely to check their BP via the app, while doctors were less likely to monitor the app for BP control during the pandemic. Conclusions: Our data demonstrate that the COVID-19 pandemic was associated with a short-term increase in morning SBP among elderly patients with hypertension in Wuhan but not other parts of China. Further study will be needed to understand if these findings extended to other parts of the world substantially affected by the virus. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03015311.

A PROSPECTIVE OBSERVATIONAL AND INTERVENTIONAL STUDY ON THE ROLE OF DOCTOR OF PHARMACY/CLINICAL PHARMACIST IN IDENTIFICATION, REPORTING AND MINIMIZATION OF DRUG-RELATED PROBLEMS IN PULMONARY AND CARDIOLOGY DEPARTMENTS OF ESI HOSPITAL

Objective: The present study aims at implementing the doctor of pharmacy services in the identification and reporting of drug-related problems in the in-patient units of cardiology and pulmonary medicine departments of ESI Hospital, Bangalore. Methods: A prospective interventional study was conducted from September 2018 to March 2019. Determination and categorization of drug-related problems (DRPs) were performed by the pharmacist using the PCNE classification scheme for drug-related problems V5.01. The DRPs identified by the pharmacist were reported and interventions made were subsequently recorded. Results: 180 drug-related problems were identified in the study, among which the major problems were drug-drug interactions (13.88%), followed by generic substitution (10%). The mean drug-related problem per patient was found to be 1.06. A total of 196 interventions were made by the clinical pharmacists among which, 109 (55.61%), 56 (28.57%), 17 (8.67%) interventions were at the prescriber, drug, patient levels, and 14 (7.14%) cases were the rest of interventions or activities. Distributions based on type and degree of acceptance of interventions showed that among 56 drug regimen change interventions proposed by the pharmacist, only 55.35% were accepted. The results further indicated that out of 68 monitoring required interventions made by the pharmacist, and among 17 cases that required counseling by the pharmacist in verbal, 77.94% and 88.36% of cases were accepted, respectively. Also, regarding the cases that required communication between the pharmacists and other healthcare professionals, 85.36% of a total of 41 samples and all of 14 adverse drug reporting cases made in a formal note form were accepted. Conclusion: The clinical pharmacist’s/doctor of pharmacy professional’s timely interventions in the patient’s drug therapy is required to prevent or minimize the occurrence and the risk of DRP. Rational drug therapy and optimal medication safety can be achieved by clinical pharmacy services.

Biomarkers of treatment success in fully sensitive pulmonary tuberculosis patients: a multicenter longitudinal study

Aim: Novel biomarkers that are able to accurately monitor tuberculosis (TB) treatment effectiveness are needed to adjust therapy and identify a need for a regimen change. Materials & methods: In our study, conducted on a cohort comprising 100 pulmonary TB patients, we analyzed the role of plasma cytokines and Toll-like receptors expression as biomarkers of treatment response. Results: Changes in toll-interacting protein (TOLLIP) and lymphocyte antigen 96 (LY96) gene expression as well as nine cytokine levels over the first 2 months were significantly associated with successful treatment outcome. Successful treatment was associated with higher serum concentration of Toll-like receptor-2. Conclusion: Our results suggest that differential expression of specific effector molecules and dynamics of selected cytokines may help to identify those responding to TB treatment early.

Assessment of Real-Life Outcomes in Schizophrenia Patients according to Compliance

Objective. To describe and compare demographics, outcomes and comorbidities in schizophrenia patients by treatment compliance. Methods. This was a cross-sectional survey of hospital- or office-based psychiatrists who saw ≥6 schizophrenia patients per week and were responsible for treatment decisions. Recruited physicians completed a patient record form (PRF) for their first 10 consulted schizophrenia patients aged ≥18. These patients voluntarily completed a patient self-completion form (PSC). Compliance was measured by subjective physician assessment. Drivers of and outcomes associated with compliance were identified by regression analyses. Results. A total of 150 physicians completed PRFs for 1489 patients (706 sometimes compliant (SC), 636 always compliant (AC)). A total of 680 patients completed a PSC (327 SC, 295 AC). AC patients were less likely to be male (52.2% vs. 58.6%; P=0.021) and unemployed (odds ratio (OR) 0.91, 95% confidence interval (CI) 0.82–1.00; P<0.001) or to have had a treatment regimen change (OR 0.56, 95% CI 0.40–0.80; P=0.001) than SC patients. AC patients were less likely to have had more comorbidities (OR 0.91, 95% CI 0.82–1.00; P=0.045) and hospitalizations in the past 12 months (OR 0.59, 95% CI 0.43–0.80; P=0.001) than SC patients. Overall, AC patients had better clinical and humanistic outcomes. Weight gain was a common side effect for all patients; SC patients with weight gain had poorer outcomes than those without weight gain. Conclusion. Schizophrenia patients that were SC experienced poorer clinical outcomes and quality of life. Weight gain may exacerbate these poorer outcomes.

The role of imaging in early detection of patients at risk for neuropathy during primary chemotherapy for ovarian carcinoma.

e18071 Background: Neuropathy is a common adverse event requiring dose reduction or regimen change in patients receiving platinum-taxane chemotherapy for ovarian cancer. Our aim was to determine whether specific biomarkers, such as skeletal muscle, visceral and subcutaneous fat cross-sectional areas, measured using computerized tomography (CT), were associated with the development of neuropathy. Analytic Morphomics, a semi-automated image analysis method, has been used to predict oncologic outcomes with immunotherapy and to identify patients at higher risk for postoperative complications from major cancer surgeries. We hypothesized that patients who required dose reductions or regimen changes would have CT imaging findings that distinguished them from their counterparts who did not require dose reduction or regimen change. Methods: All patients at our institution diagnosed with high-grade ovarian carcinoma between January 1, 2014 and December 31, 2018 were identified retrospectively. Analytic Morphomics was used to extract measures of body composition from CT images at the level of the third lumbar vertebra. Demographic and clinical characteristics were abstracted from the electronic medical record. We analyzed several binary outcomes (neuropathy, delay in chemotherapy, or dose reduction by cycle 1, 3 or 6) and used unpaired, two-tailed t-tests to compare means between each outcome group at each timepoint. Results: Of 156 patients screened for the study, 138 patients were included and had pre-treatment CT scans available and completed six cycles of platinum-taxane chemotherapy. Patients who developed neuropathy in any of the six cycles, or had a change in their chemotherapy regimen by cycle six, had higher mean visceral fat area than those who did not develop neuropathy. This finding was statistically significant throughout three cycles (p = 0.023) and six cycles (p = 0.030). Conclusions: Increased visceral fat on CT imaging was significantly associated with a higher incidence of neuropathy and change in chemotherapy regimen in patients undergoing primary platinum-taxane chemotherapy for ovarian carcinoma. Weight and BMI did not have a significant association with development of neuropathy, dose reduction, or treatment delay. Further study is needed to determine if dose reductions or regimen changes due to neuropathy can be better predicted using morphomics.