Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.

Mycobacterium tuberculosis Infection and Disease

Last Updated: September 22, 2017; Last Reviewed: September 22, 2017

Recommendations for Treating Mycobacterium Tuberculosis Infection and Disease

Treating LTBI (to prevent TB disease)

Indications:

  • (+) screening testa for LTBI, no evidence of active TB, and no prior history of treatment for active or latent TB (AI);
  • Close contact with a person with infectious TB, regardless of screening test result (AII)

Preferred Therapy (Duration of Therapy = 9 Months):

  • INH 300 mg PO daily + pyridoxine 25-50 mg PO daily (AII) or 
  • INH 900 mg PO twice weekly (by DOT) + pyridoxine 25-50 mg PO daily (BII)

Alternative Therapies:

  • RIF 600 mg PO daily x 4 months (BIII) or
  • RFB (dose adjusted based on concomitant ART) x 4 months (BIII) or
  • RPT (weight-based, 900 mg max) PO weekly + INH 15 mg/kg weekly (900 mg max) + pyridoxine 50 mg weekly x 12 weeks – in patients receiving an EFV- or RAL-based ART regimen (BIII)
    • 32.1–49.9 kg 750 mg 
    • ≥50.0 kg 900 mg
  • For persons exposed to drug-resistant TB, select anti-TB drugs after consultation with experts or with public health authorities (AII) 

Treating Active TB Disease

  • After collecting specimen for culture and molecular diagnostic tests, empiric treatment should be initiated in HIV-infected persons with clinical and radiographic presentation suggestive of HIV-related TB (AIII)
  • DOT is recommended for all patients requiring treatment for HIV-related TB (AII)
  • Please refer to the table below for TB drug dosing recommendations and to the Adult and Adolescent ARV Guidelines for dosing recommendations of ARV drugs when used with RIF or RFB.

For Drug-Sensitive TB

Intensive Phase (2 Months)

  • INH + (RIF or RFB) + PZA + EMB (AI); if drug susceptibility report shows sensitivity to INH & RIF, then EMB may be discontinued.

Continuation Phase (For Drug Susceptible TB)

  • INH + (RIF or RFB) daily (5–7 days per week) (AII)  

Total Duration of Therapy:

  • Pulmonary, drug-susceptible TB—6 months (BII)
  • Pulmonary TB & positive culture at 2 months of TB treatment—9 months (BII) 
  • Extrapulmonary TB w/CNS involvement—9 to 12 months (BII)
  • Extrapulmonary TB w/bone or joint involvement—6 to 9 months (BII)
  • Extrapulmonary TB in other sites—6 months (BII) 

For Drug-Resistant TB

Empiric Therapy for Suspected Resistance to Rifamycin +/- Resistance to Other Drugs:

  • INH + (RIF or RFB) + PZA + EMB + (moxifloxacin or levofloxacin) + (an aminoglycoside or capreomycin)
  • Therapy should be modified based on drug susceptibility results
  • A TB expert should be consulted
Resistant to INH

  • (RIF or RFB) + EMB + PZA + (moxifloxacin or levofloxacin) for 2 months (BIII); followed by (RIF or RFB) + EMB + (moxifloxacin or levofloxacin) for 7 months (BII)
Resistant to Rifamycins +/- Other Antimycobacterial Agents:
  • Therapy and duration of treatment should be individualized based on drug susceptibility, clinical and microbiological responses, and with close consultation with experienced specialists (AIII).

Other Considerations in TB Management

  • Adjunctive corticosteroid improves survival for patients with HIV-related TB involving the CNS and pericardium (AI)
  • Dexamethasone has been used for CNS disease with the following dosing schedule: 0.3–0.4 mg/kg/day for 2–4 weeks, then taper 0.1 mg/kg per week until 0.1 mg/kg, then 4 mg per day and taper by 1 mg/week; total duration of 12 weeks.
  • Prednisone or prednisolone may be used in pericardial disease (e.g., 60 mg PO daily and taper by 10 mg per day weekly; total duration 6 weeks)
  • Despite the potential of drug-drug interactions, a rifamycin remains the most potent TB drug and should remain as part of the TB regimen unless there is rifamycin-resistant isolate or the patient has a severe adverse effect that is likely to be due to the rifamycin (please refer to the table below and to the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents for dosing recommendations involving concomitant use of RIF or RFB and different antiretroviral drugs).
  • If NVP is to be added to a patient who is receiving RIF, the lead-in dose for NVP should be omitted.
  • RFB is a less potent CYP 3A4 inducer than RIF and is preferred in patients receiving HIV PIs (BIII).
  • Rifamycins administered once or twice weekly can result in development of resistance in HIV-infected patients and is not recommended for patients with TB disease (AI).
  • Paradoxical reaction that is not severe may be treated symptomatically (CIII).
  • For moderately severe paradoxical reaction, use of corticosteroid may be considered.Taper over 4 weeks (or longer) based on clinical symptoms (BIII).

Examples of Prednisone Dosing Strategies

  • In patients on a RIF-based regimen: prednisone 1.5 mg/kg/day x 2 weeks, then 0.75 mg/kg x 2 weeks
  • In patients on a RFB + boosted PI based regimen: prednisone 1.0 mg/kg/day x 2 weeks, then 0.5 mg/kg/day x 2 weeks
  • A more gradual tapering schedule over a few months may be necessary in some patients.

a Screening tests for LTBI include TST or IGRA; please see text for details regarding these tests.

Key to Abbreviations: ART = antiretroviral therapy; ARV = antiretroviral; CNS = central nervous system; DOT = directly observed therapy; EFV = efavirenz; EMB = ethambutol; INH = isoniazid; LTBI = latent tuberculosis infection; NVP = nevirapine; PI = protease inhibitor; PO = per os (oral); PZA = pyrazinamide; RAL = raltegravir; RFB = rifabutin; RIF = rifampin; RPT = rifapentine; TB = tuberculosis; TIW = thrice weekly; TST = tuberculin skin test; IGRA = interferon-gamma release assays

Dosing Recommendations for Anti-Tuberculosis Drugs for Treatment of Active TB
Drug Daily
Isoniazid 5 mg/kg (usual dose 300 mg)
Rifampina
Note: Rifampin is not recommended in patients receiving HIV PIs, ETR, RPV,
EVG/COBI or TAF
10 mg/kg (usual dose 600 mg)
Rifabutina
without HIV PIs, EFV, RPV
5 mg/kg (usual dose 300 mg)
with HIV PIs 150 mgb
with EFV 450–600 mg
withTAF or EVG/COBI containing regimens not recommended
Pyrazinamide
(weight-based dosing)
40–55 kg
1000 mg (18.2–25.0 mg/kg)

56–75 kg 1500 mg (20.0–26.8 mg/kg)
76-90 kg 2000 mg (22.2–26.3 mg/kg)
>90 kg 2000 mgc
Ethambutol

40–55 kg
800 mg (14.5–20.0 mg/kg)

56–75 kg 1200 mg (16.0–21.4 mg/kg)
76-90 kg 1600 mg (17.8–21.1 mg/kg)
>90 kg 1600 mgc

a For more detailed guidelines on use of different antiretroviral drugs with rifamycin, clinicians should refer to the Drug Interactions section of the Adult and Adolescent ARV Guidelines
b Acquired rifamycin resistance has been reported in patients with inadequate rifabutin levels while on 150 mg twice weekly dosing together with ritonavir-boosted PIs. May consider therapeutic drug monitoring when rifabutin is used with a ritonavir-boosted PI and adjust dose accordingly.
c Monitor for therapeutic response and consider therapeutic drug monitoring to assure dosage adequacy in patients who weigh >90 kg.

Key to Acronyms: COBI = cobicistat; EFV = efavirenz; EVG = elvitegravir; FTC = emtricitabine; MVC = maraviroc; NNRTI = non-nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; TAF = tenofovir alafenamide

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