ID Learning Unit: Understanding Advances in the Treatment of Latent Tuberculosis Infection among People with HIV

Tuberculosis remains the leading cause of death among people with HIV (PWH). The diagnosis of latent TB infection (LTBI) and treatment with TB preventative therapy (TPT) can reduce morbidity and mortality in this population. Historically, isoniazid has been recommended for TPT in PWH due to the absence of drug-drug interactions with most antiretroviral therapy (ART). However, newer rifamycin-based regimens are safer, shorter in duration, associated with improved adherence, and may be as or more effective than isoniazid TPT. Current guidelines have significant heterogeneity in their recommendations for TPT regimens and acceptability of drug interactions with modern ART. In this ID learning unit, we review common questions on diagnosis, treatment, and drug interactions related to the management of LTBI among PWH.

Role of Yoga for the prevention & management of COVID-19-A review

The current outbreak of the COVID-19 has declared as a global health emergency. Moreover, COVID -19 mostly affects the persons having low immunity & mortality rate is also more in such persons. The standard line of treatment for this disease is not yet established. Considering the current need-based scenario, prevention of the disease by improving the immune system is the best & ultimate way to combat this dreadful situation. Therefore, various Yoga Practices useful for immunity building, described in Ayurvedic literature are compiled through this paper, which may become helpful to improve the strength of lungs as well as general immunity of the body. This conceptual study is narrated in a clear & tabular manner under heads of the concept of immunity in Ayurveda, the importance & advantages of Pranayam & Asanas with Immuno-modulator effect of Yoga in COVID -19. All narration is given along with suitable discussion in contemporary science. Daily practices of Yoga play a crucial role in the improvement in the body defense mechanism by making comfortable & relaxed breathing with an increase in elastic recoiling of lungs but without increasing the respiratory rate. It also nourishes the specific organs by increasing the oxygen level in the blood. From that, it is reflected that these Yoga Practices can be used as supportive & preventative therapy for COVID -19 & can fulfill the above-said need.

Evaluation of the uptake of tuberculosis preventative therapy for people living with HIV in Namibia: a multiple methods analysis

Background In 2016, Namibia had ~ 230,000 people living with HIV (PLHIV) and 9154 new tuberculosis (TB) cases, including 3410 (38%) co-infected cases. TB preventative therapy (TPT), consisting of intensive case finding and isoniazid preventative therapy, is critical to reducing TB disease and mortality. Methods Between November 2014 and February 2015, data was abstracted from charts of PLHIV enrolled in HIV treatment. Fifty-five facilities were purposively selected based on patient volume, type and location. Charts were randomly sampled. The primary outcome was to estimate baseline TPT in PLHIV, using nationally weighted proportions. Qualitative surveys were conducted and summarized to evaluate TPT practices and quantify challenges encountered by health care workers (HCW). Results Among 861 PLHIV sampled, 96% were eligible for TPT services, of which 87.1% were screened for TB at least once. For PLHIV eligible for preventative therapy (646/810; 82.6%), 45.4% (294/646) initiated therapy and 45.7% (139/294) of those completed therapy. The proportion of eligible PLHIV completing TB screening, initiating preventative therapy and then completing preventative therapy was 20.7%. Qualitative surveys with 271 HCW identified barriers to TPT implementation including: lack of training (61.3% reported receiving training on TPT); misunderstandings about timing of TPT initiation (46.7% correctly reported TPT should be started with antiretroviral therapy); and variable screening practices and responsibilities (66.1% of HCWs screened for TB at every encounter). Though barriers were evident, 72.2% HCWs surveyed described their clinical performance as very good, often placing responsibility of difficulties on patients and downplaying challenges like staff shortages and medication stock outs. Conclusions In this study, only 1 in 5 eligible PLHIV completed the TPT cascade in Namibia. Lack of training, irregularities with TB screening and timing of TPT, unclear prescribing and recording responsibilities, and a clinical misperception may have contributed to suboptimal programmatic implementation. Addressing these challenges will be critical with continued TPT scale-up.

1644. “And the stick to fight TB is IPT”: Perspectives on TPT Implementation Among Senior Nurses in Rural South Africa

Background Tuberculosis (TB) disproportionately affects people living with HIV (PLH). The World Health Organization (WHO) has endorsed tuberculosis preventative therapy (TPT) in resource-limited settings with high HIV and TB burdens. South Africa has led global TPT efforts, yet implementation remains sub-optimal. Methods In a rural, impoverished region of South Africa with high TB and HIV prevalence, primary care clinic-based senior nurses were asked to participate in anonymous, semi-structured interviews assessing TPT knowledge, beliefs, and attitudes. The currently available regimen is isoniazid preventive therapy (IPT) for 12 months. Through an iterative process, a code list was generated and applied to each transcript. The data were analyzed using thematic analysis and Nvivo 12 software to identify facilitators and barriers to IPT prescribing. Results Among 22 nurses at 14 primary health clinics, 86% were female, median age 39 (IQR 31-54.8) years, with median 10.5 (IQR3-18) years of health care experience. Nurses felt that TPT was effective at preventing TB. Barriers to implementation included limited time to counsel patients due to understaffing in high-volume clinics and lack of documentation of IPT prescription in patients’ charts, which limited effective follow-up. Nurses certified in Nurse-Initiated Management of Antiretroviral Therapy (NIMART) expressed confidence in their IPT knowledge, but those not certified wanted additional training. Nurses identified patient-level factors impeding TPT implementation, including transportation, HIV-related stigma, mobility, particularly among men, and pill burden associated with length of IPT (12 months) with concurrent daily chronic medications. Facilitators included availability of IPT in both hospitals and primary care clinics, and capacity for task-shifting to other healthcare professionals (counselors, staff nurses). The impending rollout of 3HP (12 weeks of isoniazid-rifapentine) was viewed favorably. Conclusion Nurses identified limited time to counsel PLH and lack of standardized training programs as the main barriers to implementation of TB preventative therapy. Addressing these barriers will be critical to successful implementation of new TPT regimens. Disclosures All Authors: No reported disclosures

1656. Factors associated with low TB preventative therapy prescription rates among healthcare workers in rural South Africa

Background Despite South Africa’s initial successful rollout of tuberculosis preventative therapy (TPT) to reduce tuberculosis (TB) incidence among HIV-infected patients, recent data suggest prescription rates have decreased. This study aimed to identify associations with low prescription rates among healthcare workers (HCWs) in rural South Africa. Methods A cross-sectional survey was administered Nov-Dec 2019 to HCWs at a 350 bed rural district hospital and 14 primary care clinics (PCCs) in the Msinga sub-district, South Africa to obtain self-reported data on prescription rates as well as knowledge, attitudes, practices, and beliefs regarding isoniazid preventive therapy, the current TPT regimen. HCWs included professional nurses, staff nurses, counselors, and medical officers. Survey questions were consolidated into scores using exploratory factor analysis. Univariate and multivariate associations with low prescription rates, defined as < 50% of eligible patients, were determined for prescribers. Results Among 160 participants, the median (+ IQR) age was 39 (+13) years, 76% were women, 78% worked at a PCC, and 35% were prescribers, including professional nurses (82%) and medical officers (19%). The median (+ IQR) years as a HCW and managing patients living with HIV (PLH) among prescribers was 14 (+ 15.5) and 10 (+ 11.5) years, respectively. Compared to prescribers, non-prescribers reported more stigma (71% v. 54%; p=0.04) and placed less priority on prevention compared to treatment (32% v. 58%; p< 0.01). Among prescribers (n=54), univariate analysis identified that patient nondisclosure (OR 4.17 95% CI 1.23-14.14; p=0.02) was associated with low TPT prescription rates. Poor self-reported knowledge also trended towards significance (OR 5.23 95% CI 0.85-32.08; p=0.07). After multivariate analysis, only perceived patient nondisclosure was significantly associated with low prescription TPT rates (aOR 4.17 95% CI 1.23-14.14; p=0.02). Conclusion HCWs who believed their patients had not disclosed that they were taking TPT were significantly less likely to prescribe it to their patients. Strengthening HCW training about indications for and mortality benefit of TPT as well as stigma reduction is critical to enhancing TPT implementation. Disclosures All Authors: No reported disclosures

Characterization and validation of a preventative therapy for hypertrophic cardiomyopathy in a murine model of the disease

Currently there is an unmet need for treatments that can prevent hypertrophic cardiomyopathy (HCM). Using a murine model we previously identified that HCM causing cardiac troponin I mutation Gly203Ser (cTnI-G203S) is associated with increased mitochondrial metabolic activity, consistent with the human condition. These alterations precede development of the cardiomyopathy. Here we examine the efficacy of in vivo treatment of cTnI-G203S mice with a peptide derived against the α-interaction domain of the cardiac L-type calcium channel (AID-TAT) on restoring mitochondrial metabolic activity, and preventing HCM. cTnI-G203S or age-matched wt mice were treated with active or inactive AID-TAT. Following treatment, targeted metabolomics was utilized to evaluate myocardial substrate metabolism. Cardiac myocyte mitochondrial metabolic activity was assessed as alterations in mitochondrial membrane potential and flavoprotein oxidation. Cardiac morphology and function were examined using echocardiography. Cardiac uptake was assessed using an in vivo multispectral imaging system. We identified alterations in six biochemical intermediates in cTnI-G203S hearts consistent with increased anaplerosis. We also reveal that AID-TAT treatment of precardiomyopathic cTnI-G203S mice, but not mice with established cardiomyopathy, restored cardiac myocyte mitochondrial membrane potential and flavoprotein oxidation, and prevented myocardial hypertrophy. Importantly, AID-TAT was rapidly targeted to the heart, and not retained by the liver or kidneys. Overall, we identify biomarkers of HCM resulting from the cTnI mutation Gly203Ser, and present a safe, preventative therapy for associated cardiomyopathy. Utilizing AID-TAT to modulate cardiac metabolic activity may be beneficial in preventing HCM in “at risk” patients with identified Gly203Ser gene mutations.