What is the recommended tuberculosis (TB) treatment regimen in patients with Human Immunodeficiency Virus (HIV)?

From the Guidelines

For HIV-positive patients with tuberculosis (TB), a standard regimen consists of two months of isoniazid, rifampin, pyrazinamide, and ethambutol (HRZE) followed by four months of isoniazid and rifampin (HR), for a total of six months of treatment, as recommended by the American Thoracic Society/ Centers for Disease Control and Prevention/Infectious Diseases Society of America 1. This regimen is based on the principles of therapy and revised recommendations for the treatment of tuberculosis in HIV-infected adults, which are identical to those for HIV-uninfected adults, with some exceptions 1. The treatment regimen may be given by daily or intermittent administration, but daily or three times weekly therapy in the continuation phase is recommended for patients with advanced HIV disease, defined as CD4 cell counts < 100/l 1. Some key considerations for the treatment of TB in HIV-positive patients include:

• The minimum duration of treatment should be six months, even for patients with culture-negative tuberculosis 1.
• Prolongation of the continuation phase to 7 months (a total of 9 months treatment) should be strongly considered if there is evidence of a slow or suboptimal response 1.
• Directly observed therapy (DOT) and other adherence-promoting strategies should be used in all patients with HIV-related tuberculosis 1.
• All patients with tuberculosis should be advised to undergo voluntary counseling and HIV testing, and efforts should be made to engage all patients with a new diagnosis of HIV infection in HIV care during their treatment for tuberculosis 1. It is essential to note that rifampin interacts significantly with many antiretrovirals, so regimen adjustments are often necessary, and dolutegravir-based regimens with two NRTIs are preferred due to fewer interactions 1. Additionally, all TB/HIV co-infected patients should receive pyridoxine (vitamin B6, 25-50mg daily) to prevent peripheral neuropathy, and cotrimoxazole prophylaxis to prevent other opportunistic infections, and close monitoring for immune reconstitution inflammatory syndrome (IRIS) is essential, especially in those with advanced HIV disease 1.

From the FDA Drug Label

For this reason, therapeutic decisions for the impaired host must be individualized Since patients co-infected with HIV may have problems with malabsorption, screening of antimycobacterial drug levels, especially in patients with advanced HIV disease, may be necessary to prevent the emergence of MDRTB. (In patients with concomitant HIV infection, the physician should be aware of current recommendation of CDC. It is possible these patients may require a longer course of treatment)

The treatment regimen for TB in HIV patients should be individualized. Patients co-infected with HIV may require:

• Screening of antimycobacterial drug levels to prevent the emergence of MDRTB
• A longer course of treatment as recommended by the CDC 2 3

From the Research

TB Regimen in HIV

• The treatment and prevention of tuberculosis in HIV-infected patients present significant challenges 4.
• In patients with drug-susceptible organisms, treatment initially with three- and four-drug followed by two-drug regimens used for 6 to 9 months is efficacious 4.
• A 2-month regimen of daily rifampin and pyrazinamide has been compared to a 12-month regimen of daily isoniazid in preventing tuberculosis in persons with HIV infection, with similar safety and efficacy 5.
• A 6-month regimen containing a potent combination of bedaquiline, pretomanid, linezolid, and moxifloxacin is a new standard for people with and without HIV 6.

Treatment Duration

• Recent clinical trials have shown that among adults and adolescents, treatment duration can be decreased to 4 months with repurposed therapeutics for drug-sensitive tuberculosis 6.
• A 9-month regimen resulted in a similar outcome at the end of treatment but a significantly lower bacteriological recurrence rate compared with a 6-month thrice-weekly regimen 7.
• The optimal regimen and duration of therapy for drug-sensitive tuberculosis is still an unresolved issue 4.

Preventive Therapy

• Isoniazid preventive therapy should be given to HIV-infected patients who are tuberculin positive and considered in selected patients who are anergic 4.
• Twice-weekly isoniazid preventive therapy for 6 months or rifampicin and pyrazinamide for 2 months provided similar overall protection against tuberculosis in HIV-1-infected, PPD-positive adults 8.
• The duration of isoniazid preventive therapy is still an unresolved issue 4.