Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Podcasts
  • Subscriptions

HIV and multidrug-resistant tuberculosis: overlapping epidemics

Anna S. Dean, Matteo Zignol, Dennis Falzon, Haileyesus Getahun, Katherine Floyd
European Respiratory Journal 2014 44: 251-254; DOI: 10.1183/09031936.00205413
Anna S. Dean
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matteo Zignol
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dennis Falzon
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haileyesus Getahun
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine Floyd
Global Tuberculosis Programme, World Health Organization, Geneva, Switzerland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: floydk@who.int
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

To the Editor:

People infected with Mycobacterium tuberculosis and HIV are much more likely to develop active tuberculosis (TB) than people with M. tuberculosis but without HIV [1]. Patients infected with multidrug-resistant (MDR)-TB (defined as resistance to at least rifampicin and isoniazid, the two most powerful anti-TB drugs) require longer, more expensive treatment regimens than drug-susceptible TB, with poorer treatment success [2], [3]. Therefore, MDR-TB poses a major challenge to the control of TB, with an estimated global disease incidence in 2012 of ∼450 000 cases (95% CI 300 000–600 000) [4]. Although HIV is a powerful risk factor for all forms of TB and institutional outbreaks of MDR-TB among people living with HIV have been reported [5], population-level data on the association between HIV infection and MDR-TB are limited.

We explored the relationship between HIV infection and MDR-TB disease using data reported by member states to the World Health Organization (WHO) within the context of the Global Project on Anti-TB Drug Resistance Surveillance. The data were aggregated numbers of cases reported from either drug resistance surveys or continuous surveillance systems. Such surveys are epidemiological studies designed to measure drug resistance among a representative sample of notified pulmonary TB patients. Continuous surveillance is based on routine drug susceptibility testing of all bacteriologically confirmed TB patients. Subnational level data that were not representative of the entire country were excluded from the analysis, except for the Russian Federation and Ukraine, which are high MDR-TB burden countries for which high quality national level data were not available. The data included in the analysis met the criteria for data quality and national representativeness provided in detail elsewhere [4], [6]. The laboratory methods used for diagnosis were endorsed by WHO.

For each country, the relationship between HIV infection and MDR-TB disease was investigated by logistic regression to calculate odds ratios and 95% confidence intervals, using Stata (version 12; StataCorp, College Station, TX, USA). For countries with data from multiple years, robust standard errors accounted for within-country time dependencies. In order to minimise bias, data for a given year were excluded if ≤25% of reported TB patients had a documented HIV test result. 41 countries, accounting for 25% of the estimated global MDR-TB burden in 2012, met the inclusion criteria for ≥1 year. Most were high-income countries and/or in the European Region. Only four countries were in the African region, which accounted for 75% of the global number of HIV-positive TB cases in 2012 [4]. Of these 41 countries, odds ratios could be calculated for 24 countries; the other 17 countries reported no HIV-positive MDR-TB cases (table 1). Complete HIV and MDR-TB data were available for 104 781 TB patients from 1997–2012.

View this table:
  • View inline
  • View popup
Table 1– Odds of multidrug-resistant (MDR) tuberculosis (TB) disease in HIV-positive patients compared with HIV-negative patients

For 11 of the 24 countries for which the analysis was performed, HIV-positive TB patients had a significantly higher odds (p<0.05) of MDR-TB disease than HIV-negative TB patients (table 1). Seven of these countries were in eastern Europe and central Asia: Estonia, Kazakhstan, Latvia, the Republic of Moldova, the Russian Federation, the Ukraine and Uzbekistan. For almost all of these 11 countries, the prevalence of MDR-TB among newly diagnosed TB cases (table 1) was higher than the estimated global average of 3.6% (95% CI 2.1–5.1%) in 2012 [4]. Although the odds ratio was highest in Kuwait, only low numbers of HIV-positive cases were reported. HIV-positive TB patients in the USA had a lower odds of MDR-TB disease than HIV-negative patients.

As data were included if ≥75% of reported TB patients had a documented HIV test, the possibility of bias due to missing data cannot be ruled out. Although a positive association between HIV infection and MDR-TB disease was demonstrated in less than half of the countries, a recent systematic review and meta-analysis found an odds of MDR-TB in HIV-positive patients that was 1.24 times (95% CI 1.04–1.43) higher than in HIV-negative patients [7]. A subgroup analysis showed that this association was stronger for primary MDR-TB disease than acquired MDR-TB disease, which supports previous findings [8]. However, most of these studies were from institutional settings, where outbreaks are known to occur more commonly in HIV-positive patients [9]. At the population level, a detailed analysis of surveillance data from the Republic of Moldova showed that, even after adjustment for potential confounders, a positive association HIV and MDR-TB existed [10].

Among those 11 countries with a positive association between HIV infection and MDR-TB disease, there was wide variation in the estimated prevalence of HIV among incident TB cases in 2012 (table 1) [4]. Given that the analysis was performed using aggregated rather than individual patient data, there are likely to be risk factors common to HIV-positive and MDR-TB patients that could not be explored in our analysis, such as shared behaviours or population characteristics. Further investigation is needed for specific high risk groups, such as prisoners or people living in congregate settings, miners, or injecting drug users. Additionally, the relationship between HIV and MDR-TB probably depends on the epidemiological setting. In the USA, where a negative association was observed between HIV infection and MDR-TB disease, investigation into the demographics of these patients is required in order to identify potential confounders. However, a cross-sectional study in eight states did not demonstrate a significant association between HIV infection and MDR-TB disease [11]. HIV has been shown to be an independent risk factor for drug resistance acquired during treatment in California [12].

Data were only available for three countries listed among both the 27 high MDR-TB burden countries and 41 high TB/HIV burden countries: Nigeria, the Russian Federation and the Ukraine. In order to better understand the relationship between HIV infection and MDR-TB, more high quality data are needed from other high burden countries. This includes the Democratic Republic of Congo, Ethiopia, Myanmar, South Africa and Vietnam. In these five countries, the percentage of estimated cases of MDR-TB that were detected and notified in 2012 ranged from just 2.2% to 30% and the percentage of TB patients with a known HIV status in 2012 ranged from 13 to 66%, excluding South Africa [4]. This is probably a reflection of low levels of testing for MDR-TB and HIV among TB patients as well as underreporting. Priorities in these countries should include integrated TB and HIV services and programmes, with universal access to HIV testing and routine and prompt TB drug susceptibility testing for patients suspected to have MDR-TB. This must be underpinned by greater awareness of healthcare workers, increased laboratory capacity, and improved data management and reporting [13]. The roll-out of rapid diagnostic tests and the use of MDR-TB treatment models that include community-based care could rapidly increase MDR-TB case notification and enrolment on second-line treatment, ultimately limiting spread [14]. Development of region- and country-specific comprehensive responses, including research for better diagnosis, treatment and scale-up of quality services, is essential [15].

Acknowledgments

All authors are staff members of WHO. The authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions or policies of WHO.

Footnotes

  • Conflict of interest: None declared.

  • This article is one of a selection of articles published as ERJ Open papers, as part of an initiative agreed between the European Respiratory Society and the World Health Organization.

  • Received December 13, 2013.
  • Accepted January 25, 2014.
  • © ERS 2014

ERJ Open articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 3.0.

References

  1. ↵
    1. Selwyn PA,
    2. Hartel D,
    3. Lewis VA,
    4. et al
    . A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. N Engl J Med 1989; 320: 545–550.
    OpenUrlCrossRefPubMedWeb of Science
  2. ↵
    1. Migliori GB,
    2. Sotgiu G,
    3. Gandhi NR,
    4. et al
    . Drug resistance beyond extensively drug-resistant tuberculosis: individual patient data meta-analysis. Eur Respir J 2013; 42: 169–179.
    OpenUrlAbstract/FREE Full Text
  3. ↵
    1. Falzon D,
    2. Gandhi N,
    3. Migliori GB,
    4. et al
    . Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes. Eur Respir J 2013; 42: 156–168.
    OpenUrlAbstract/FREE Full Text
  4. ↵
    World Health Organization. Global Tuberculosis Report 2013. www.who.int/tb/publications/global_report/en/index.html Date last accessed: November 1, 2013. Date last updated: 2013
  5. ↵
    1. Frieden TR,
    2. Sherman LF,
    3. Maw KL,
    4. et al
    . A multi-institutional outbreak of highly drug-resistant tuberculosis: epidemiology and clinical outcomes. JAMA 1996; 276: 1229–1235.
    OpenUrlCrossRefPubMedWeb of Science
  6. ↵
    World Health Organization. Guidelines for surveillance of drug resistance in tuberculosis. 4th Edn. http://whqlibdoc.who.int/publications/2009/9789241598675_eng.pdf Date last accessed: August 6, 2013. Date last updated: 2009
  7. ↵
    1. Mesfin YM,
    2. Hailemariam D,
    3. Biadglign S,
    4. et al
    . Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis. PLoS ONE 2014; 9: e82235.
    OpenUrlCrossRefPubMed
  8. ↵
    1. Suchindran S,
    2. Brouwer ES,
    3. Van Rie A
    . Is HIV infection a risk factor for multi-drug resistant tuberculosis? A systematic review. PLoS ONE 2009; 4: e5561.
    OpenUrlCrossRefPubMed
  9. ↵
    1. Wells CD,
    2. Cegielski JP,
    3. Nelson LJ,
    4. et al
    . HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis 2007; 196 Suppl. 1:S86–S107.
    OpenUrlAbstract/FREE Full Text
  10. ↵
    1. Jenkins HE,
    2. Plesca V,
    3. Ciobanu A,
    4. et al
    . Assessing spatial heterogeneity of multidrug-resistant tuberculosis in a high-burden country. Eur Respir J 2012; 42: 1291–1301.
    OpenUrlPubMedWeb of Science
  11. ↵
    1. Moonan PK,
    2. Teeter LD,
    3. Salcedo K,
    4. et al
    . Transmission of multidrug-resistant tuberculosis in the USA: a cross-sectional study. Lancet Infect Dis 2013; 13: 777–784.
    OpenUrlCrossRefPubMedWeb of Science
  12. ↵
    1. Porco TC,
    2. Oh P,
    3. Flood JM
    . Antituberculosis drug resistance acquired during treatment: an analysis of cases reported in California, 1994–2006. Clin Infect Dis 2013; 56: 761–769.
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Falzon D,
    2. Jaramillo E,
    3. Wares F,
    4. et al
    . Universal access to care for multidrug-resistant tuberculosis: an analysis of surveillance data. Lancet Infect Dis 2013; 13: 690–697.
    OpenUrlCrossRefPubMedWeb of Science
  14. ↵
    1. Nardell E,
    2. Dharmadhikari A
    . Turning off the spigot: reducing drug-resistant tuberculosis transmission in resource-limited settings. Int J Tuberc Lung Dis 2010; 14: 1233–1243.
    OpenUrlPubMed
  15. ↵
    1. Getahun H,
    2. Gunneberg C,
    3. Granich R,
    4. et al
    . HIV infection–associated tuberculosis: the epidemiology and the response. Clin Infect Dis 2010; 50: S201–S207.
    OpenUrlAbstract/FREE Full Text
View Abstract
PreviousNext
Back to top
View this article with LENS
Vol 44 Issue 1 Table of Contents
European Respiratory Journal: 44 (1)
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
HIV and multidrug-resistant tuberculosis: overlapping epidemics
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Citation Tools
HIV and multidrug-resistant tuberculosis: overlapping epidemics
Anna S. Dean, Matteo Zignol, Dennis Falzon, Haileyesus Getahun, Katherine Floyd
European Respiratory Journal Jul 2014, 44 (1) 251-254; DOI: 10.1183/09031936.00205413

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
HIV and multidrug-resistant tuberculosis: overlapping epidemics
Anna S. Dean, Matteo Zignol, Dennis Falzon, Haileyesus Getahun, Katherine Floyd
European Respiratory Journal Jul 2014, 44 (1) 251-254; DOI: 10.1183/09031936.00205413
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Agora

  • Airway immune responses to COVID-19 vaccination in COPD patients
  • Wider access to rifapentine-based regimens is needed for TB care globally
  • Screening for PVOD in heterozygous EIF2AK4 variant carriers
Show more Agora

Research letters

  • Impact of depression and anxiety on exacerbation risk in bronchiectasis
  • Respiratory management of drowning-associated ARF
  • Mitochondrial DNA as biomarker of survival in RA-ILD
Show more Research letters

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society