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

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 27, 2019; Last Reviewed: September 27, 2019

Recommendations for Treating Mycobacterium Tuberculosis Infection and Disease
Treating LTBI to Prevent TB Disease

Indications:
  • Positive screening testa for LTBI, no evidence of active TB disease, and no prior history of treatment for active disease or latent TB infection (AI);
  • Close contact with a person with infectious TB, regardless of screening test result (AII)
Preferred Therapy:
  • Isoniazid 300 mg PO daily plus pyridoxine 25–50 mg PO daily (AI)
Duration of Therapy:
  • 9 months
Alternative Therapies:
  • Rifapentine (see weight-based dosing below) PO once weekly plus isoniazid 15 mg/kg PO once weekly (900 mg maximum) plus pyridoxine 50 mg PO once weekly for 12 weeks (AII). Note: Rifapentine is only recommended for patients receiving an efavirenz- or raltegravir-based ART regimen.
    • Rifapentine Weekly Dose (maximum 900 mg)
      • Weighing 32.1–49.9 kg: 750 mg
      • Weighing ≥50.0 kg: 900 mg, or
        • Rifampin 600 mg PO daily for 4 months (BI) or
        • 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 persons with HIV 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 Table 3 (below) for TB drug dosing recommendations and to the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations of ARV drugs when used with rifampin or rifabutin.
For Drug-Sensitive TB

Intensive Phase (2 Months):
  • Isoniazid plus (rifampin or rifabutin) plus pyrazinamide plus ethambutol (AI)
  • If drug susceptibility report shows sensitivity to isoniazid and rifampin, then ethambutol may be discontinued.
Continuation Phase (for Drug-Susceptible TB):
  • Isoniazid plus (rifampin or rifabutin) daily (AII)
Total Duration of Therapy:
  • Pulmonary, drug-susceptible TB: 6 months (BII)
  • Pulmonary TB and positive culture at 2 months of TB treatment, severe cavitary disease or disseminated extrapulmonary TB: 9 months (BII)
  • Extrapulmonary TB w/CNS involvement: 9 to 12 months (BII)
  • Extrapulmonary TB in other sites: 6 months (BII)
For Drug-Resistant TB

Empiric Therapy for Resistance to Rifamycin plus/minus Resistance to Other Drugs:
  • Isoniazid plus pyrazinamide plus ethambutol plus (moxifloxacin or levofloxacin) plus (an aminoglycoside or capreomycin)
  • Therapy should be modified once rifampin resistance is confirmed and based on drug susceptibility results to provide ≥5 active drugs.
Resistant to Isoniazid:
  • (Moxifloxacin or levofloxacin) plus (rifampin or rifabutin) plus ethambutol plus pyrazinamide for 6 months (BII)
Resistant to Rifamycins plus/minus Other Antimycobacterial Agents:
  • Therapy should be individualized based on drug susceptibility test results, clinical and microbiological responses, to include ≥5 active drugs, and with close consultation with experienced specialists (AIII).
Duration:
  • 12 to 24 months (see the Management of Drug-Resistant TB section above for discussion of shorter course therapy)
Other Considerations in TB Management
  • Adjunctive corticosteroid improves survival for patients with HIV-related TB involving the CNS (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.
  • 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 a rifamycin-resistant isolate is detected, or the patient has a severe adverse effect that is likely due to the rifamycin (please refer to the table below and to the Adult and Adolescent Antiretroviral Guidelines for dosing recommendations involving concomitant use of rifampin or rifabutin and different ARV drugs).
  • If NVP is to be added to the ARV regimen of a patient who is receiving RIF, the lead-in dose for NVP should be omitted.
  • Intermittent rifamycins can result in development of resistance in patients with HIV and is not recommended (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 for IRIS
  • In patients on a rifampin -based regimen: prednisone 1.5 mg/kg/day for 2 weeks, then 0.75 mg/kg for 2 weeks
  • In patients on a rifabutin plus boosted PI based regimen: prednisone 1.0 mg/kg/day for 2 weeks, then 0.5 mg/kg/day for 2 weeks
  • A more gradual tapering schedule over a few months may be necessary in some patients.
  • Pre-emptive prednisone regimen: 40 mg/day for 2 weeks then 20 mg/day for 2 weeks
a Screening tests for LTBI include TST or IGRA; see text for details regarding these tests.

Key: ART = antiretroviral therapy; ARV = antiretroviral; CNS = central nervous system; DOT = directly observed therapy; EFV = efavirenz; IGRA = interferon-gamma release assay; LTBI = latent tuberculosis infection; NVP = nevirapine; PI = protease inhibitor; PO = orally; RAL = raltegravir; TB = tuberculosis; TST = tuberculin skin test

Table 3. Dosing Recommendations for Anti-TB Drugs for Treatment of Active Drug Sensitive TB
TB Drug ARV Drugs Daily Dose
Isoniazid All ARVs 5 mg/kg (usual dose 300 mg)
Rifampina,b

Note: DTG, RAL, and MVC doses need to be adjusted when used with rifampin
With HIV PIs, DOR, ETR, RPV, BIC, or EVG/c Not recommended
With TAF Use with cautionc at dose indicated below
With other ARV drugs 10 mg/kg (usual dose 600 mg)
Rifabutina

Note: DOR and RPV doses need to be adjusted when used with rifabutin
With PI with COBI, TAF, BIC, or EVG/c - containing regimens Not recommended
With DTG, RAL, EFV, DOR, RPV 5 mg/kg (usual dose 300 mg)
With HIV PIs with RTV 150 mgd
With EFV 450–600 mg
Pyrazinamide All ARVs Weight-Based Dosing
  • Weighing 40–55 kg: 1,000 mg (18.2–25.0 mg/kg)
  • Weighing 56–75 kg: 1,500 mg (20.0–26.8 mg/kg)
  • Weighing 76–90 kg: 2,000 mg (22.2–26.3 mg/kg)
  • Weighing >90 kg: 2,000 mge
Ethambutol All ARVs Weight-Based Dosing
  • Weighing 40–55 kg: 800 mg (14.5–20.0 mg/kg)
  • Weighing 56–75 kg: 1,200 mg (16.0–21.4 mg/kg)
  • Weighing 76-90 kg: 1,600 mg (17.8–21.1 mg/kg)
  • Weighing >90 kg: 1,600 mge
a For more detailed guidelines on use of different ARV drugs with rifamycin, clinicians should refer to the Drug-Drug Interactions section of the Adult and Adolescent Antiretroviral Guidelines

b Higher doses may be needed in the treatment of TB meningitis. Expert consultation is advised.

c This combination has not been tested in patients to confirm PK and virologic efficacy among patients taking full dose ART and TB regimens.             

d Acquired rifamycin resistance has been reported in patients with inadequate rifabutin levels while on 150 mg twice weekly dosing together with RTV-boosted PIs. May consider TDM when rifabutin is used with an RTV-boosted PI and adjust dose accordingly.

e Monitor for therapeutic response and consider TDM to assure dosage adequacy in patients weighing >90 kg.

Key: ARV = antiretroviral; ART = antiretroviral therapy; BIC = bictegravir; COBI = cobicistat; DOR = doravirine; DTG = dolutegravir; EFV = efavirenz; ETR = etravirine; EVG = elvitegravir; EVG/c = elvitegravir/cobicistat; FTC = emtricitabine; MVC = maraviroc; PI = protease inhibitor; PK = pharmacokinetic; RAL = raltegravir; RPV = rilpivirine; RTV = ritonavir; TAF = tenofovir alafenamide; TB = tuberculosis; TDM = therapeutic drug monitoring

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