Risk Factors

  • Unlike other opportunistic infections that only manifest in the presence of  substantially reduced CD4+ counts, TB can occur at all CD4+ counts1

– although the risk of developing TB increases with decreasing CD4+ count1

  • People living with HIV (PLWHIV) in congregate settings such as prisons and refugee centres have a higher risk and incidence of TB than people residing outside of these settings2

– crowded living conditions facilitate transmission of TB, including multi-drug-resistant TB2

  • HIV-infected injection drug users are at greater risk of TB infection and disease compared with other HIV-infected individuals3

– for more information on substance use in PLWHIV, consult the drug use section of myHIVclinic


Risk factors for MDR-TB4

  • Previous TB treatment
  • Birth, travel or work in an area endemic for MDR-TB
  • History of poor adherence
  • Sputum smear positive after 2 months of TB therapy, or culture positive at 3 months
  • Homelessness/hostel living


Risk factors for miliary/disseminated TB5

With progression of immunosuppression in advanced HIV infection (CD4+ cell counts <200 cells/µL), disseminated and miliary TB are more common than at higher CD4+ cell counts (>500 cells/µL).5

Prevention of TB

Antiretroviral therapy (ART) is the most important factor in the reduction of TB incidence in PLWHIV; however, PLWHIV receiving ART are still highly vulnerable to TB.6

The Three I’s

Three key interventions known as ‘The Three I’s’ have been identified and sanctioned by the World Health Organization (WHO) to reduce the burden of TB in PLWHIV.6

  • Intensified Case Finding (ICF): regularly screening PLWHIV particularly those spending time in congregate settings for the symptoms of TB and promptly diagnosing and treating infected individuals

– the same process should be followed for household contacts of infected individuals6

  • Isoniazid Preventive Therapy (IPT): can be given to PLWHIV without active TB, reducing the risk of developing active TB by 33–67% for up to 4 years6

– Studies conducted in Brazil and South Africa among PLWHIV who received both ART and IPT showed a 76 and 89% reduction in TB risk, respectively7,8
– In a recent randomised, double-blind, placebo-controlled trial comparing 6-month versus 36-month IPT for latent TB in adults with HIV infection in Botswana:9

  • 36-month IPT reduced the incidence of active TB by 43% compared with 6-month IPT
  • the most striking benefit of continued IPT was for patients who had a positive tuberculin skin test, who had a 74% reduction in the incidence of active TB compared with the control group9

– while TST is not a requirement for initiating IPT in PLWHIV, PLWHIV who have a positive TST benefit more from IPT than those with a negative TST10 
– IPT is recommended for PLWHIV6

  • in areas with prevalence of latent TB infection > 30%
  • with documented latent TB infection, or exposure to an infected individual
  • combined use of IPT and ART in PLWHIV significantly reduces the incidence of active TB6–8
  • Infection Control (IC): preventing the spread of TB to vulnerable patients, health care workers, the community and those living in congregate settings6

For full guidelines on ICF and IPT in PLWHIV see WHO Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings.10

For additional information on latent TB treatment, see Akolo C, et al. (2010) Treatment of latent tuberculosis infection in HIV infected persons (Review).12



  1. Martinson NA, Hoffman CJ, Chaisson RE. Epidemiology of Tuberculosis and HIV: recent advances in understanding and responses. Proc Am Thorac Soc 2011;8:228–293. 
  2. Getahun H, Gunneberg C, Granich R, Nunn P. HIV Infection-Associated Tuberculosis: The Epidemiology and the Response. Clin Infec Dis 2010;50:S201–7. 
  3. Deiss RG, Rodwell TC, Garfein RS. Tuberculosis and illicit drug use: review and update. Clin Infect Dis 2009;48:72–82. 
  4. British HIV Association. Guidelines for the Treatment of TB/HIV Coinfection 2011. Accessed 25 November 2011.
  5. Sharma SK, Mohan A, Sharma A, Mitra DK. Miliary tuberculosis: new insights into an old disease. Lancet Infect Dis 2005;5:415–430. 
  6. World Health Organization. Three I’s Meeting (2008).  Accessed 25 November 2011.
  7. Golub JE, Saraceni V, Cavalcante SC, 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):1441–1448. 
  8. Golub JE, Pronyk P, Mohapi L, et al. Isoniazid preventive therapy, HAART and tuberculosis risk in HIV-infected adults in South Africa: a prospective cohort. AIDS 2009;23(5):631–636.
  9. Samandari T, Agizew TB, Nyirenda S, 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;377:1588–1598. 
  10. World Health Organization. Policy on collaborative TB/HIV activities (2012). Accessed 13 April 2012.
  11. World Health Organization. Guidelines for Intensified Tuberculosis Case-finding and Isoniazid Preventive Therapy for People Living with HIV in Resource-constrained Settings. Accessed 25 November 2011.
  12. Akolo C, Adetifa I, Shepperd S, et al. Treatment of latent tuberculosis infection in HIV infected persons (Review). Cochrane Database Syst Rev. 2010;(1):CD000171.