Incidence and Prediction of Symptoms and Drug Sensitivity Reactions in Persons Receiving Weekly Rifapentine Plus Isoniazid (3HP) for Treatment of Latent Tuberculosis Infection Público

Sadowski, Claire (Spring 2019)

Permanent URL: https://etd.library.emory.edu/concern/etds/sn009z640?locale=pt-BR
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Abstract

Background: Approximately a quarter of the world is latently infected with Mycobacterium tuberculosis, the causative agent of tuberculosis disease. Three months of once weekly rifapentine plus isoniazid therapy for latent tuberculosis infections is now recommended in a wide variety of populations, however, the development of signs and symptoms and possible hypersensitivity reactions have not been fully characterized. We sought to describe the patterns of sign and symptom development, characterize possible hypersensitivity reactions, and identify risk factors for hypersensitivity in patients on 3HP therapy.

Methods: We analyzed the signs and symptom data on the 1002 participants undergoing 3HP therapy in TBTC Study 33. We examined the patterns of symptom development across all participants from baseline up to 4 monthly visits. A modified definition of hypersensitivity from the PREVENT TB trial was used to characterize possible hypersensitivity reactions across all study visits. Bivariate analyses and multivariate logistic regression were used to identify possible sociodemographic predictors of hypersensitivity in this population.

Results: We found that symptoms commonly reported as developing during 3HP treatment include headache (27%), nausea (20%), and fatigue (22%). The most common pattern of symptom progression was development during the first month, followed by resolution. Reported symptoms during 3HP treatment tended to be mild in nature and did not affect treatment completion in most cases. We identified 56 out of 1002 (5.6%) participants who had possible hypersensitivity reactions. Factors that were associated with hypersensitivity reactions in multivariate logistic regression included older age (>=45 years) (OR=2.02 [1.14, 3.56]) and use of any concomitant medications 14 days prior to treatment start (OR=3.82 [1.66, 8.81]). Hypersensitivity reactions were a treatment limiting factor in this population.

Conclusions: Our findings suggest that if patients develop symptoms while on 3HP treatment, these symptoms tend to be mild and resolve after the first month of treatment. We suggest close monitoring of patients undergoing 3HP treatment who are older in age and who take concomitant medications, especially during the first month of treatment. Increased education of physicians and patients regarding the signs and symptoms associated with possible hypersensitivity reactions as well as the potential risk factors is recommended.

Table of Contents

CHAPTER 1: LITERATURE REVIEW……………………………………………………………………..….1

             The Global Tuberculosis Epidemic………………………………………………………………...1

             Epidemiology of Tuberculosis in the United States…………………………………………....2

             Latent Tuberculosis in the United States and Other Low Incidence Countries……........5

             Epidemiology of Tuberculosis in High Incidence Countries………………………………....7

             Latent Tuberculosis in South Africa and Other High Burden Countries……………........9

             Importance of Treating LTBI and Difficulties………………………………………….……....10

                            Diagnosing LTBI…………………………………………………………..………..………11

                            Determining Reactivation Risk and Initiating Treatment………………….........12

             Treating Latent Tuberculosis Infections……………………………………………………...…13

                            Rationale and Examples of Treatment Regimens…………….……..……….....…13

                            9H Therapy Versus 3HP Therapy…………………………………………………..…..14

                            Reasons for Not Completing Treatment for LTBI…………………………….....…14

                            Description and Support for 3HP Therapy…………………………………..…..…..16

             Symptoms and Drug-Related Adverse Events During LTBI Treatment………..….........19

                            Known Reactions and Safety Concerns with Isoniazid………………….….….....19

                            Safety Concerns with Rifamycin Drugs and the “Flu-Like” Syndrome............21

             Drug Hypersensitivity Reactions in Treatment for LTBI………………………………........23

Conclusion…………………………………………………………………………………………….…........25

CHAPTER 2: MANUSCRIPT……………………………………………………………………………….…26

Introduction……………………………………………………………………………………………......…26

Methods……………………………………………………………………………………………………......29

                            Study Population and Setting…………………………………………………………..29

                            Data Source and Study Variables…………………………………………………..…..29

                            Data Analysis……………………………………………………………..………………..30

                            Ethical Considerations…………………………………………………………………...31

Results…………………………………………………………………………………………………….....…33

                            Sociodemographic Statistics……………………………………………………….…..33

                            Adverse Events……………………………………………………………………………..33

                            Symptom Progression and Patterns at Study Visits……………………..……......34

                            Possible Hypersensitivity Reactions…………………………………..……………....35

Discussion………………………………………..………………………………………………………........36

REFERENCES…………………………………………………………………………………………………...40

TABLES…………………………………………………………………………………………………………..47

FIGURES………………………………………………………………………………………………….……..52

CHAPTER III: PUBLIC HEALTH IMPLICATIONS……………………………………………..........…53

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