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Drug Safety

, Volume 36, Issue 11, pp 1087–1096 | Cite as

Adverse Events During Treatment of Drug-Resistant Tuberculosis: A Comparison Between Patients With or Without Human Immunodeficiency Virus Co-infection

  • Evans Sagwa
  • Nunurai Ruswa
  • Jean Paul Musasa
  • Aukje K. Mantel-Teeuwisse
Original Research Article

Abstract

Introduction

In settings such as Namibia with a high prevalence of human immunodeficiency virus (HIV) and drug-resistant (DR) tuberculosis (TB) co-infection, interactions and adverse events associated with second-line anti-TB and antiretroviral medicines pose a unique challenge in the treatment of both infections.

Objective

The main objective of this study was to compare the absolute risks and risk factors for commonly observed adverse events (occurring in >20 % of patients) during DR-TB treatment in HIV-infected and HIV-uninfected patients.

Methods

This was a retrospective cohort analysis of patients treated for DR-TB between January 2008 and February 2010 at the Kondja DR-TB ward in Walvis Bay, Namibia. Data were anonymously collected from patients’ treatment records, using a structured form. The data were then analyzed using descriptive statistics, while 2 × 2 contingency tables stratified by HIV status were employed to examine specific risk factor and adverse event relationships, using Epi Info 3.4.3 statistical software.

Eighteen adverse events were studied but, because of the small sample size of patients, only the four most frequent ones (occurring in >20 % of patients) were included in the risk factor analysis. The risk factors were a treatment period of <4 weeks; treatment with any highly active antiretroviral therapy (HAART) regimen; specific treatment with a zidovudine (AZT)-based HAART regimen, a cycloserine-based DR-TB regimen or an amikacin-based DR-TB regimen; female gender; baseline body weight ≤45 kg; and age 30 ≥years.

Results

Of the 57 DR-TB patients who were included in the analysis, 31 (53 %) were co-infected with HIV. When stratified by HIV status, DR-TB patients had similar exposure to specific DR-TB medicines and comparable demographic and clinical characteristics, except for age, as HIV-infected patients were on average 6.5 years older than HIV-uninfected patients (P = 0.007). Of the 18 studied adverse events, tinnitus (40 %), joint pain (26 %), hearing loss (23 %) and nausea (21 %) were the four most commonly observed events. Only for abdominal pain was there a statistically significant difference in the risk of occurrence between HIV-infected patients and HIV-uninfected patients (26 versus 4 %, P = 0.02).

The risk ratios (RRs) for the association between treatment with a cycloserine-based DR-TB regimen and occurrence of joint pain did not differ much between HIV-infected and HIV-uninfected patients (RR 4.3 in HIV-infected patients, P = 0.03; RR 5 in HIV-uninfected patients, P = 0.08). Similarly, although some differences in the RRs were observed between the two HIV status groups, the differences were not statistically significant for tinnitus, hearing loss or nausea. In some instances, HIV status appeared to modify the effect of the association of some of the risk factors and adverse event occurrence, but the wide and overlapping confidence intervals were inconclusive.

Conclusion

Generally, the absolute risks and risk factors for adverse events were similar between HIV-infected and HIV-uninfected patients treated for DR-TB in our Namibian cohort of 57 patients. Although our findings of comparable adverse event risks between DR-TB and DR-TB/HIV co-infected patients are encouraging, they are inconclusive because of the low statistical power of our study. We recommend a prospective study with a larger sample size that would increase the power and therefore the confidence in the results.

Keywords

Human Immunodeficiency Virus Hearing Loss Joint Pain Pyrazinamide Human Immunodeficiency Virus Status 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to thank H.G.M. Leufkens, P. Souverein, B. van Wyk, J. Rohde, F. Mavhunga, M. Malakia, A. Mengistu, J. Nwokike, D. Mabirizi, P. Dhliwayo, A. Stergachis, R. Laing and T. Rennie for their contributions to this study. Special thanks are due to B. Nemery and S. Gordon of the Pan African Thoracic Society Course in Methods for Epidemiologic, Clinical and Operational Research (PATS-MECOR) for their technical assistance in the interpretation of the study findings and for their advice on writing the manuscript. TB patient care and treatment is a Government- and donor-funded service freely provided by health facilities of the Ministry of Health and Social Services in Namibia.

Conflict of interest

E Sagwa, N Ruswa, JP Musasa and AK Mantel-Teeuwisse have no conflicts of interest that are directly relevant to the content of this manuscript. The Department of Pharmacoepidemiology and Clinical Pharmacology at Utrecht Institute for Pharmaceutical Sciences, which employs Aukje Mantel-Teeuwisse, has received unrestricted research funding from the Netherlands Organisation for Health Research and Development (ZonMW), the Dutch Health Care Insurance Board (CVZ), the Royal Dutch Pharmacists Association (KNMP), the private–public funded Top Institute Pharma (www.tipharma.nl, which includes co-funding from universities, government, and industry), the EU Innovative Medicines Initiative (IMI), the EU 7th Framework Program (FP7), the Dutch Medicines Evaluation Board and the Dutch Ministry of Health and Industry (including GlaxoSmithKline, Pfizer, and others).

Funding Source

Funding for this study was personally provided by Evans Sagwa, using his own resources as part of his research towards the Master of Public Health degree at the University of the Western Cape, Cape Town, South Africa.

Author contributions

Evans Sagwa conceived and designed the study; collected and analyzed the data; and drafted, finalized and submitted the manuscript. Nunurai Ruswa and Jean Paul Musasa reviewed the study protocol and manuscript. Aukje Mantel-Teeuwisse contributed to the interpretation of the study findings, provided guidance on writing of the manuscript and critically reviewed all drafts of the manuscript.

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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Evans Sagwa
    • 1
    • 2
    • 3
    • 6
  • Nunurai Ruswa
    • 4
  • Jean Paul Musasa
    • 5
  • Aukje K. Mantel-Teeuwisse
    • 2
  1. 1.School of Public HealthUniversity of the Western CapeCape TownSouth Africa
  2. 2.Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical PharmacologyUtrecht UniversityUtrechtThe Netherlands
  3. 3.Management Sciences for HealthWindhoekNamibia
  4. 4.National Tuberculosis and Leprosy ProgrammeWindhoekNamibia
  5. 5.Ministry of Health and Social ServicesWalvis BayNamibia
  6. 6.Klein WindhoekNamibia

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