Isoniazid/rifapentine (for LTBI)
A 1-month regimen of daily isoniazid plus rifapentine has been evaluated in a randomized, open-label, phase 3 trial and found to be noninferior to 9 months of isoniazid alone for preventing TB in patients with HIV who were living in areas of high TB prevalence or who had evidence of latent TB infection (LTBI).[102]Swindells S, Ramchandani R, Gupta A, et al. One month of rifapentine plus isoniazid to prevent HIV-related tuberculosis. N Engl J Med. 2019 Mar 14;380(11):1001-11.
https://www.doi.org/10.1056/NEJMoa1806808
http://www.ncbi.nlm.nih.gov/pubmed/30865794?tool=bestpractice.com
US guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV include the regimen as an alternative option for treatment of LTBI in people with HIV.[64]National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: mycobacterium tuberculosis infection and disease. 2024 [internet publication].
https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/mycobacterium
However, it is not currently recommended in the National Tuberculosis Controllers Association and Centers for Disease Control and Prevention guidelines.[71]Sterling TR, Njie G, Zenner D, et al. Guidelines for the treatment of latent tuberculosis infection: recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020 Feb 14;69(1):1-11.
https://www.cdc.gov/mmwr/volumes/69/rr/rr6901a1.htm
http://www.ncbi.nlm.nih.gov/pubmed/32053584?tool=bestpractice.com
Oral bedaquiline/levofloxacin/linezolid-containing regimens (for MDR-TB)
In one multicenter randomized controlled trial in adults with multidrug-resistant (MDR)/rifampin-resistant (RR)-TB, an all-oral 6-month levofloxacin, bedaquiline, and linezolid-containing MDR/RR-TB regimen was associated with a significantly improved 24-month World Health Organization-defined treatment outcome compared with traditional injectable-containing regimens.[103]Esmail A, Oelofse S, Lombard C, et al. An all-oral 6-month regimen for multidrug-resistant tuberculosis: a multicenter, randomized controlled clinical trial (the NExT study). Am J Respir Crit Care Med. 2022 May 15;205(10):1214-27.
http://www.ncbi.nlm.nih.gov/pubmed/35175905?tool=bestpractice.com
However, drug toxicity occurred frequently in both intervention arms.
8-week regimens
In the TRUNCATE-TB trial, patients with rifampin-susceptible pulmonary TB were randomized to either standard treatment (rifampin and isoniazid for 24 weeks with pyrazinamide and ethambutol for the first 8 weeks) or to a strategy involving initial treatment with an 8-week regimen containing bedaquiline and linezolid, extended treatment for persistent clinical disease, monitoring after treatment, and retreatment for relapse.[104]Paton NI, Cousins C, Suresh C, et al. Treatment strategy for rifampin-susceptible tuberculosis. N Engl J Med. 2023 Mar 9;388(10):873-87.
https://www.nejm.org/doi/10.1056/NEJMoa2212537?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/36808186?tool=bestpractice.com
The study found that an 8-week regimen containing bedaquiline and linezolid was noninferior to standard treatment with respect to the risk of a composite clinical outcome (death, ongoing treatment, or active disease) at week 96.[104]Paton NI, Cousins C, Suresh C, et al. Treatment strategy for rifampin-susceptible tuberculosis. N Engl J Med. 2023 Mar 9;388(10):873-87.
https://www.nejm.org/doi/10.1056/NEJMoa2212537?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed
http://www.ncbi.nlm.nih.gov/pubmed/36808186?tool=bestpractice.com
Novel vaccine candidates
The M72/AS01E candidate vaccine contains an immunogenic fusion protein (M72) derived from two Mycobacterium tuberculosis antigens (Mtb32A and Mtb39A), combined with the AS01E adjuvant system. In a phase 2b double-blind randomized placebo-controlled trial, M72/AS01E provided approximately 50% protection against progression to active pulmonary tuberculosis for 3 years in M tuberculosis-infected, HIV-negative adults.[105]Tait DR, Hatherill M, Van Der Meeren O, et al. Final analysis of a trial of M72/AS01E vaccine to prevent tuberculosis. N Engl J Med. 2019 Dec 19;381(25):2429-39.
http://www.ncbi.nlm.nih.gov/pubmed/31661198?tool=bestpractice.com
[106]World Health Organization. Vaccines and immunization: investigational vaccine candidate M72/AS01E. Jun 2020 [internet publication].
https://www.who.int/news-room/questions-and-answers/item/vaccines-and-immunization-investigational-vaccine-candidate-m72-as01e