Tuberculosis, Active


  • M. tuberculosis 
  • M. bovis 


  • Hx: cough >2 wks, fever, night sweats, weight loss, hemoptysis, SOB, chest pain; can also present as an acute pneumonia or systemic illness
  • CXR: upper lobe infiltrate classic (may be cavitary); lymphadenopathy
  • Clinical and radiographic manifestations may be atypical in HIV+ persons, especially with low CD4 count (< 200): lower-lobe infiltrates, adenopathy alone, and even normal CXR.
  • Extrapulmonary disease more common in HIV+ pts, especially with low CD4 counts.
  • TB often subclinical in HIV+ pts, particularly with low CD4. Disease can be "unmasked" on ART
  • Immune reconstitution inflammatory syndrome (IRIS) may result in worsening of TB symptoms on TB and HIV treatment


  • Characteristic Sx (see "Clinical")
  • Sputum AFB smear: 50% sensitive. Lower sensitivity in HIV+ pts.
  • AFB Cx: 80% sensitive
  • Nucleic acid amplification (NAA) tests: sensitive, specific for sputum AFB smear +; less sensitive for smear-negative sputum (negative NAA does not exclude TB if sputum AFB smear-negative); expensive; also low sensitivity for non-respiratory specimens
  • QuantiFERON-TB Gold In-tube and T.SPOT.TB (interferon-gamma release assays [IGRA]) FDA-approved. Limited data in HIV+; T.SPOT.TB probably more sensitive than QuantiFERON-TB Gold In-tube in HIV+. Used for identifying latent TB infection. Does not distinguish between latent infection and active disease.
  • GeneXpert MTB/RIF test (FDA-approved) can detect M. tb and rifampin resistance directly in clinical specimens in approximately 2 hours.
  • New tests not yet FDA-approved but endorsed by WHO:
    • Line-probe assays (e.g., MTBDRplus and MTBDRsl by Hain Lifescience) can detect M. tb in culture or directly in clinical specimens; can also detect genotypic mutations associated with resistance: INH, rifampin, injectable agents, fluoroquinolones.



  • Isoniazid (INH) 5mg/kg (300 mg max) + rifampin (RIF) 10 mg/kg (600 mg max) + pyrazinamide (PZA) 15-30 mg/kg (2 g max) + ethambutol (EMB) 15-25 mg/kg (1.6g max) + pyridoxine (vitamin B6) 50 mg (all PO once-daily x 8 wks), then INH + RIF (same doses PO once-daily); see below for duration
  • Can use rifabutin in place of RIF in persons on PIs, NNRTIs, integrase inhibitors (but not elvitegravir), methadone. Dose adjustments necessary (see specific ART module for drug dosing recommendations).
  • Check drug susceptibilities; treat with at least 2 drugs to which isolate is susceptible
  • Rx duration determined by site of disease, response to therapy. Pulmonary and most extrapulmonary: 6 mos (except if at high risk for relapse--see "Other Information"); CNS: 12 mos; bone/joint: 9-12 mos.
  • Refer to health department so pt can receive directly-observed therapy (DOT)
  • Dosing less frequent than daily is possible if via DOT, though daily (7 or 5 days per week) often preferred.
  • RIF 10 mg/kg (600 mg max) can be given with EFV (standard 600 mg dose; may need to increase to 800 mg, especially if patient weighs >60 kg)


  • INH 10-15 mg/kg (300 mg max) + RIF 10-20 mg/kg (600 mg max) + PZA 15-30 mg/kg (2 g max) + EMB 15-20 mg/kg (1 g max), all PO once daily.
  • Use EMB only if can monitor visual acuity (e.g. >8 yrs) or drug resistance strongly suspected
  • Can use rifabutin in place of RIF in persons on HIV PIs, NNRTI, integrase inhibitors. Dose adjustments necessary
  • Check drug susceptibilities; treat with at least 2 drugs to which isolate is susceptible.
  • Rx duration determined by site of disease, response to therapy
  • Refer to health department so pt can receive directly observed therapy (DOT).
  • Dosing less frequent than daily is possible if via DOT, though daily (7 or 5 days per week) often preferred.


  • Respiratory isolation for cough >2 wks + abnormal CXR while evaluating for TB
  • Can discontinue isolation if TB evaluation is negative with 3 sputa (expectorated or induced) are smear-negative. However, if high suspicion of active TB, start treatment.
  • If smear + or on Rx, can discontinue isolation after 2 wks of Rx plus clinical improvement, plus AFB smear-negative (3 specimens).

General Treatment Issues

  • Refer all cases to local health department for treatment and contact investigation.
  • DOT preferred for both adults and children
  • MDR-TB (resistance to at least INH and RIF) should be managed in consultation with expert in resistant TB infections.
  • Caution regarding drug interactions, toxicity, paradoxical worsening (IRIS). Consult expert.
  • If HIV+ and CD4 < 100, give daily TB treatment for first 60 days, then no less frequent than 3x/wk.
  • When to start ART in relation to starting TB therapy (DHHS Guidelines):
    • If already on ART at time of TB diagnosis, continue ART and start TB Rx
    • If not on ART, timing depends on CD4 count:
      • CD4 < 50: start ART within 2 wks of TB Rx
      • CD4 >50: start ART within 8-12 wks of TB Rx

Selected Drug Comments




Least potent of first-line agents but must be in regimen until sensitivities known


Pyridoxine limits peripheral neuropathy due to INH


Allows for 6-month (short-course) therapy. Hepatotoxicity, hyperuricemia possible.


Fewer drug interactions than rifampin


Crucial drug in first-line therapy


  • Pts should be followed by health department while on therapy. Seen monthly for signs/Sx of toxicity, and sputum Cx to document negative Cx. Generally not followed after completion of therapy, but should return if signs/Sx of TB recur.


  • Based on ATS/CDC/IDSA Guidelines. See ref below. Includes recommendation to extend treatment to 9 mos if cavitary disease plus Cx + after 2 mos of tx


  1. Meintjes G, Brust JCM, Nuttall J, et al. Management of active tuberculosis in adults with HIV. Lancet HIV. 2019;6(7):e463-e474.  [PMID:31272663]
  2. Furin J, Cox H, Pai M. Tuberculosis. Lancet. 2019;393(10181):1642-1656.  [PMID:30904262]
  3. Nahid P, Dorman SE, Alipanah N, et al. Executive Summary: Official American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America Clinical Practice Guidelines: Treatment of Drug-Susceptible Tuberculosis. Clin Infect Dis. 2016;63(7):853-67.  [PMID:27621353]
  4. Horsburgh CR, Barry CE, Lange C. Treatment of Tuberculosis. N Engl J Med. 2015;373(22):2149-60.  [PMID:26605929]
  5. Mfinanga SG, Kirenga BJ, Chanda DM, et al. Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial. Lancet Infect Dis. 2014;14(7):563-71.  [PMID:24810491]
  6. Boehme CC, Nabeta P, Hillemann D, et al. Rapid molecular detection of tuberculosis and rifampin resistance. N Engl J Med. 2010;363(11):1005-15.  [PMID:20825313]

    Comment: Performing test once was 98% sensitive for smear-positive pulmonary TB and 73% sensitive for smear-negative TB; performing 3 tests increased sensitivity to 90% for smear-negative disease. Detection of rifampin resistance was 98% sensitive and specific.

  7. Sterling TR, Pham PA, Chaisson RE. HIV infection-related tuberculosis: clinical manifestations and treatment. Clin Infect Dis. 2010;50 Suppl 3:S223-30.  [PMID:20397952]

    Comment: Update on clinical manifestations, treatment issues, and drug interactions.

  8. Mazurek GH, Jereb J, Vernon A, et al. Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010. MMWR Recomm Rep. 2010;59(RR-5):1-25.  [PMID:20577159]

    Comment: Updated CDC guidelines for use of QuantiFERON-TB Gold, QuantiFERON-TB Gold In-tube, and T.SPOT.TB

  9. Abdool Karim SS, Naidoo K, Grobler A, et al. Timing of initiation of antiretroviral drugs during tuberculosis therapy. N Engl J Med. 2010;362(8):697-706.  [PMID:20181971]

    Comment: Initiating ART during TB treatment decreased risk of death by 56% compared to waiting until after completion of anti-TB Rx. Benefit of starting within 4 weeks (vs. 8-12 weeks) of TB Rx start seen only among pts with CD4 < 50

  10. Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009;58(1):7-10.  [PMID:19145221]
  11. Havlir DV, Kendall MA, Ive P, et al. Timing of antiretroviral therapy for HIV-1 infection and tuberculosis. N Engl J Med 2011; 365:1482.

    Comment: Primary endpoint was death or new AIDS-defining event among persons starting ART within 2 weeks vs. 8-12 weeks after starting anti-TB Rx. Benefit of starting at 2 weeks seen only among persons with CD4 < 50. IRIS risk high.

  12. Blanc FX, Sok T, Laureillard D, et al. Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis. N Engl J Med 2011; 365:1471.

    Comment: Among persons with low CD4 (median 25), risk of death was 34% lower in persons starting HAART within 2 weeks of anti-TB therapy compared to persons starting HAART 8 weeks after anti-TB therapy.

  13. Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. June 14, 2019

    Comment: Updated reference on drug-drug interactions.

  14. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. October 25, 2018

    Comment: Updated reference on drug-drug interactions.

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Last updated: August 5, 2019