Adverse Events Occurrence in Multidrug Resistant Tuberculosis and Human Immunodeficiency Virus in KwaZulu-Natal, South Africa Public

Abstract

Multidrug resistant tuberculosis (MDR TB) and HIV epidemics have converged geographically in South Africa leading to current guidelines to treat both diseases concurrently. In this study the affect of concurrent treatment on laboratory adverse events (AEs) was examined, with the hypothesis that concurrent treatment would lead to increased adverse events in coinfected populations compared to MDR TB only groups. Frequency and severity of MDR TB symptoms, laboratory AEs and MDR TB adverse events was compared across HIV-positive (n=250) and HIV-negative (n=99) groups with both groups demonstrating similar AE distribution and severity over the first 14 clinic visits. Bivariate and multivariate logistic analysis was then conducted to determine association between patient baseline characteristics (N=349) and experiencing a laboratory AE scoring at least a 2 on the DAIDS scale. Baseline age and sputum smear result were included in the final multivariate logistic model, but neither were significant at P<0.05. The lack of difference in AE frequency or severity in coinfected and non-coinfected populations indicates that current guidelines for concurrent treatment should be supported. All findings are interim and are subject to change as data continues to be collected.

Table of Contents

Table of Contents

Chapter I . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Literature Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Epidemiology of Tuberculosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Drug Susceptible Tuberculosis with HIV Coinfection . . . . . . . . . . . . . . .2

Tuberculosis Drug-resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6

Impact of Drug Resistance on HIV Patients . . . . . . . . . . . . . . . . . . . . 11

MDR TB Treatment in HIV Patients . . . . . . . . . . . . . . . . . . . . . . . . . . 15

HIV treatment in MDR TB patients & Drug-drug Interactions . . . . . . . 18

MDR TB associated Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . 20

HIV associated Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22

MDR TB/HIV Adverse Events . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

Adherence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Current Gaps in the Literature . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .29

Study Aims . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .30

Chapter II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .31

Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32

Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34

Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .40

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .52

Figures/Figure Legends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56

Chapter III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57

Summary and Public Health Implications . . . . . . . . . . . . . . . . . . . . . . 57

About this Master's Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Rollins School of Public Health
Department	Epidemiology
Subfield / Discipline	Global Epidemiology - MPH & MSPH
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Health Sciences, Public Health Health Sciences, Epidemiology
Mot-clé	HIV coinfection MDR TB adverse events
Committee Chair / Thesis Advisor	Gandhi, Neel R, Emory University
Partnering Agencies	Does not apply (no collaborating organization)

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