Skip to main content

Advertisement

SpringerLink
Log in

Treatment of Latent Tuberculosis Infection in HIV: Shorter or Longer?

  • Co-infections (C Benson, Section Editor)
  • Published:
Current HIV/AIDS Reports Aims and scope Submit manuscript

Abstract

Nine months of daily isoniazid is efficacious in treating latent M. tuberculosis infection, but completion rates are low, limiting treatment effectiveness. In 2011, three important studies were published involving novel regimens for the treatment of latent M. tuberculosis infection. At least 36 months of isoniazid was more effective than 6 months of isoniazid in one study, but not in another—both of which were conducted among tuberculin skin test positive HIV-infected adults living in high tuberculosis incidence settings. Three months of once-weekly isoniazid plus rifapentine or twice-weekly isoniazid plus rifampin (both given under direct observation) resulted in tuberculosis rates similar to those seen with 6 months of isoniazid among HIV-infected persons in high tuberculosis incidence settings. Three months of once-weekly, directly-observed isoniazid plus rifapentine was at least as effective as 9 months of daily isoniazid among predominantly HIV-uninfected persons living in low and medium tuberculosis incidence countries. The 3-month once-weekly isoniazid plus rifapentine regimen demonstrates promise for treatment of latent M. tuberculosis infection in HIV-infected persons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Selwyn PA, Hartel D, Lewis VA, Schoenbaum EE, Vermund SH, Klein RS, 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(9):545–50. Often-cited paper on the high annual risk of progression to active tuberculosis among HIV-infected persons with M. tuberculosis infection who do not receive treatment for either infection.

    Article  PubMed  CAS  Google Scholar 

  2. Wood R, Maartens G, Lombard CJ. Risk factors for developing tuberculosis in HIV-1-infected adults from communities with a low or very high incidence of tuberculosis. J Acquir Immune Defic Syndr. 2000;23(1):75–80.

    Article  PubMed  CAS  Google Scholar 

  3. Global Tuberculosis Control 2011; Geneva, Switzerland. WHO Report 2011. 2011 Nov. 7; 1–258. Available from: http://www.who.int/tb/publications/global_report/en/

  4. Akolo C, Adetifa I, Shepperd S, Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev. 2010;1:CD000171.

    PubMed  Google Scholar 

  5. Diaz A, Diez M, Bleda MJ, Aldamiz M, Camafort M, Camino X, et al. Eligibility for and outcome of treatment of latent tuberculosis infection in a cohort of HIV-infected people in Spain. BMC Infect Dis. 2010;10:267.

    Article  PubMed  Google Scholar 

  6. Horsburgh CR, Goldberg S, Bethel J, Chen S, Colson PW, Hirsch-Moverman Y, et al. Latent TB infection treatment acceptance and completion in the United States and Canada. Chest. 2010;137(2):401–9.

    Article  PubMed  Google Scholar 

  7. Guidelines for intensified tuberculosis case finding and isoniazid preventive therapy for people living with HIV in resource constrained settings. Geneva, Switzerland. WHO 2011.

  8. Menzies D, Dion M-J, Rabinovitch B, Mannix S, Brassard P, Schwartzman K. Treatment completion and costs of a randomized trial of rifampin for 4 months versus isoniazid for 9 months. Am J Respir Crit Care Med. 2004;170(4):445–9.

    Article  PubMed  Google Scholar 

  9. Lardizabal A, Passannante M, Kojakali F, Hayden C, Reichman LB. Enhancement of treatment completion for latent tuberculosis infection with 4 months of rifampin. Chest. 2006;130(6):1712–7.

    Article  PubMed  CAS  Google Scholar 

  10. Page KR, Sifakis F, Montes de Oca R, Cronin WA, Doherty MC, Federline L, et al. Improved adherence and less toxicity with rifampin vs isoniazid for treatment of latent tuberculosis: a retrospective study. Arch Intern Med. 2006;166(17):1863–70.

    Article  PubMed  CAS  Google Scholar 

  11. Madhi SA, Nachman S, Violari A, Kim S, Cotton MF, Bobat R, et al. Primary isoniazid prophylaxis against tuberculosis in HIV-exposed children. N Engl J Med. 2011;365(1):21–31.

    Article  PubMed  CAS  Google Scholar 

  12. Quigley MA, Mwinga A, Hosp M, Lisse I, Fuchs D, Porter JDH, et al. Long-term effect of preventive therapy for tuberculosis in a cohort of HIV-infected Zambian adults. AIDS. 2001;15(2):215–22.

    Article  PubMed  CAS  Google Scholar 

  13. Johnson JL, Okwera A, Hom DL, Mayanja H, Mutuluuza Kityo C, Nsubuga P, et al. Duration of efficacy of treatment of latent tuberculosis infection in HIV-infected adults. AIDS. 2001;15(16):2137–47.

    Article  PubMed  CAS  Google Scholar 

  14. •• Samandari T, Agizew TB, Nyirenda S, Tedla Z, Sibanda T, Shang N, et al. 6-month versus 36-month isoniazid preventive treatment for tuberculosis in adults with HIV infection in Botswana: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;377(9777):1588–98. A study of the effect of prolonged isoniazid treatment among HIV-infected persons in a high tuberculosis incidence area (Botswana), where the risk of M. tuberculosis re-infection is high. Also assessed tuberculosis risk according to tuberculin skin test status and receipt of antiretroviral therapy.

    Article  PubMed  CAS  Google Scholar 

  15. •• Martinson NA, Barnes GL, Moulton LH, Msandiwa R, Hausler H, Ram M, et al. New regimens to prevent tuberculosis in adults with HIV infection. N Engl J Med. 2011;365(1):11–20. Conducted among HIV-infected persons in South Africa, this study demonstrated no significant difference in the protective effect of four regimens: 3 months of once-weekly isoniazid + rifapentine (directly-observed), 3 months of twice-weekly isoniazid + rifampin (directly-observed), 6 months of daily isoniazid (self-administered), and up to 6 years of daily isoniazid (self-administered). The continuous isoniazid regimen was poorly tolerated.

    Article  PubMed  CAS  Google Scholar 

  16. •• Sterling TR, Villarino ME, Borisov AS, Shang N, Gordin F, Bliven-Sizemore E, et al. Three months of rifapentine and isoniazid for latent tuberculosis infection. N Engl J Med. 2011;365(23):2155–66. Although most of the study population was HIV-uninfected, this study conducted in low and medium tuberculosis incidence countries demonstrated that 3 months of once-weekly isoniazid + rifapentine (directly-observed) was at least as effective as 9 months of daily isoniazid (self-administered). The tolerability of both regimens was similar.

    Article  PubMed  CAS  Google Scholar 

  17. Badri M, Wilson D, Wood R. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Lancet. 2002;359(9323):2059–64.

    Article  PubMed  Google Scholar 

  18. Santoro-Lopes G, de Pinho AMF, Harrison LH, Schechter M. Reduced risk of tuberculosis among Brazilian patients with advanced human immunodeficiency virus infection treated with highly active antiretroviral therapy. Clin Infect Dis. 2002;34(4):543–6.

    Article  PubMed  Google Scholar 

  19. Jones JL, Hanson DL, Dworkin MS, DeCock KM, Adult/Adolescent Spectrum of HIV Disease Group. HIV-associated tuberculosis in the era of highly active antiretroviral therapy. The Adult/Adolescent Spectrum of HIV Disease Group. Int J Tuberc Lung Dis. 2000;4(11):1026–31.

    PubMed  CAS  Google Scholar 

  20. Lawn SD, Wood R, De Cock KM, Kranzer K, Lewis JJ, Churchyard GJ. Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources. Lancet Infect Dis. 2010;10(7):489–98.

    Article  PubMed  Google Scholar 

  21. Lawn SD, Harries AD, Williams BG, Chaisson RE, Losina E, De Cock KM, et al. Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it? Int J Tuberc Lung Dis. 2011;15(5):571–81.

    Article  PubMed  CAS  Google Scholar 

  22. www.clinicaltrials.gov [Internet]. [cited 2012 Mar. 29]. Available from: http://clinicaltrials.gov/ct2/show/NCT00463086?term=Isoniazid+Plus+%28Highly+Active+Antiretroviral+Therapy%29+HAART+to+Prevent+Tuberculosis+%28TB%29+in+HIV-infected+Persons+%28HAART-IPT%29&rank=1

  23. www.clinicaltrials.gov [Internet]. [cited 2012 Mar. 29]. Available from: http://clinicaltrials.gov/ct2/results?term=Early+Antiretroviral+Treatment+and%2For+Early+Isoniazid+Prophylaxis+Against+Tuberculosis+in+HIV-infected+Adults+

  24. Golub JE, Saraceni V, Cavalcante SC, Pacheco AG, Moulton LH, King BS, et al. The impact of antiretroviral therapy and isoniazid preventive therapy on tuberculosis incidence in HIV-infected patients in Rio de Janeiro, Brazil. AIDS. 2007;21(11):1441–8.

    Article  PubMed  Google Scholar 

  25. Golub JE, Pronyk P, Mohapi L, Thsabangu N, Moshabela M, Struthers H, et al. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS. 2009;23(5):631–6.

    Article  PubMed  Google Scholar 

  26. • Gordin FM, Matts JP, Miller C, Brown LS, Hafner R, John SL, et al. A controlled trial of isoniazid in persons with anergy and human immunodeficiency virus infection who are at high risk for tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS. N Engl J Med. 1997;337(5):315–20. As has been subsequently demonstrated in other studies, there was no significant decrease in tuberculosis risk among anergic HIV-infected persons who received isoniazid preventive therapy.

    Article  PubMed  CAS  Google Scholar 

  27. Dodd LE, Wilkinson RJ. Isoniazid preventive therapy in HIV infection. Lancet. 2011;377(9777):1548–50.

    Article  PubMed  Google Scholar 

  28. Comstock GW, Baum C, Snider DE. Isoniazid prophylaxis among Alaskan Eskimos: a final report of the bethel isoniazid studies. Am Rev Respir Dis. 1979;119(5):827–30.

    PubMed  CAS  Google Scholar 

  29. Mwinga A, Hosp M, Godfrey-Faussett P, Quigley M, Mwaba P, Mugala BN, et al. Twice weekly tuberculosis preventive therapy in HIV infection in Zambia. AIDS. 1998;12(18):2447–57.

    Article  PubMed  CAS  Google Scholar 

  30. sterlit. Supplementary Appendix. New England Journal of Medicine [Internet]. 2011 Dec. 8;365(23):1–23. Available from: http://nejm.org

  31. van Halsema CL, Fielding KL, Chihota VN, Russell EC, Lewis JJC, Churchyard GJ, et al. Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AIDS. 2010;24(7):1051–5.

    Article  PubMed  Google Scholar 

  32. Balcells ME, Thomas SL, Godfrey-Faussett P, Grant AD. Isoniazid preventive therapy and risk for resistant tuberculosis. Emerg Infect Dis. 2006;12(5):744–51.

    Article  PubMed  CAS  Google Scholar 

  33. Mtei L, Matee M, Herfort O, Bakari M, Horsburgh CR, Waddell R, et al. High rates of clinical and subclinical tuberculosis among HIV-infected ambulatory subjects in Tanzania. Clin Infect Dis. 2005;40(10):1500–7.

    Article  PubMed  Google Scholar 

  34. Vernon A, Burman W, Benator D, Khan A, Bozeman L. Acquired rifamycin monoresistance in patients with HIV-related tuberculosis treated with once-weekly rifapentine and isoniazid. Tuberc Trials Consortium Lancet. 1999;353(9167):1843–7.

    CAS  Google Scholar 

  35. Weiner M, Bock N, Peloquin CA, Burman WJ, Khan A, Vernon A, et al. Pharmacokinetics of rifapentine at 600, 900, and 1,200 mg during once-weekly tuberculosis therapy. Am J Respir Crit Care Med. 2004;169(11):1191–7.

    Article  PubMed  Google Scholar 

  36. Getahun H, Kittikraisak W, Heilig CM, Corbett EL, Ayles H, Cain KP, et al. Development of a standardized screening rule for tuberculosis in people living with HIV in resource-constrained settings: individual participant data meta-analysis of observational studies. PLoS Med. 2011;8(1):e1000391.

    Article  PubMed  Google Scholar 

  37. Centers for Disease Control and Prevention CDC. Recommendations for use of an isoniazid-rifapentine regimen with direct observation to treat latent mycobacterium tuberculosis infection. MMWR Morb Mortal Wkly Rep. 2011;60:1650–3.

    Google Scholar 

  38. Short-Course (3-Month) Therapy with Weekly Isoniazid-Rifapentine Is NOT RECOMMENDED for HIV-Infected Patients Receiving Antiretroviral Therapy (December20, 2011). http://aidsinfo.nih.gov/Guidelines/Default.aspx. Accessed March 26, 2012.

  39. Ziakas PD, Mylonakis E. 4 months of rifampin compared with 9 months of isoniazid for the management of latent tuberculosis infection: a meta-analysis and cost-effectiveness study that focuses on compliance and liver toxicity. Clin Infect Dis. 2009;49(12):1883–9.

    Article  PubMed  Google Scholar 

  40. Holland DP, Sanders GD, Hamilton CD, Stout JE. Costs and cost-effectiveness of four treatment regimens for latent tuberculosis infection. Am J Respir Crit Care Med. 2009;179(11):1055–60.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

Funding support: NIAID K24 AI 65298 (TRS).

Disclosure

No potential conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Division of Infectious Diseases, Vanderbilt Comprehensive Care Clinic, One Hundred Oaks, 719 Thompson Lane, Suite 37189, Nashville, TN, 37204, USA

    Anna K. Person

  2. Division of Infectious Diseases, A2209 Medical Center North, 1161 21st Avenue South, Nashville, TN, 37232, USA

    Timothy R. Sterling

Authors
  1. Anna K. Person
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Timothy R. Sterling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anna K. Person.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Person, A.K., Sterling, T.R. Treatment of Latent Tuberculosis Infection in HIV: Shorter or Longer?. Curr HIV/AIDS Rep 9, 259–266 (2012). https://doi.org/10.1007/s11904-012-0120-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11904-012-0120-1

Keywords

Search

Navigation