Tuberculosis (TB) in the US: Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis (Mtb), is a leading cause of mortality, killing more than a million people worldwide\^1. In the United States an important recent trend has been the plateauing of the active TB disease incidence at 3.0 cases per 100,000 persons\^2. Current US TB control guidelines recommend treating all subjects with LTBI to prevent progression to active TB. However, treatment is given with the antibiotic Isoniazid (INH) for 6-9 months, Rifampin and Rifabutin for 4 months or INH with Rifapentine for 3 months and as subjects with LTBI are asymptomatic, treatment default rates are understandably high (\>10% on average)\^3-5. It is well known that a subset of patients with LTBI have higher risk of progression to active TB. Because of the high treatment default rate, a number of these "high risk" subjects receive incomplete or no preventive therapy and contribute to the incidence of active TB cases in the US. Currently, there are no strategies being implemented to identify those at highest risk and consequently treatment approaches follow the "one size fits all" paradigm. In the investigators preliminary study done at the Saint Louis University (SLU) Infectious Diseases Clinic, the investigators used an online risk calculator (TSTin3D.com)\^6 to retrospectively determine the cumulative lifetime risk of progression to active TB for adults receiving treatment for latent TB. The investigators found that current practice leads to equal rates of treatment completion i.e. 57% in the high risk for active TB disease (TBhi) group (\>10% cumulative risk of progression based on medical risk factors) compared to 59% for those at lowest risk (TBlow, \<10% cumulative risk of progression). It is not standard of care to use a scoring system like the TSTin3d.com to assess the risk. There are certain risk factors like having HIV or being on immunosuppression that physicians ask about but most physicians do not do a quantitative risk assessment. Treatment choices are usually based on convenience and concern for side effects but the most common regimen is daily INH for 6-9 months.

This data implies that the current "treat everyone and hope that therapy is completed" approach leads to a significant number of people in the TBhi group remaining untreated and at high risk of progression to active TB. A recent advance has been a CDC approved regimen using Isoniazid (INH) and Rifapentine given weekly as directly observed therapy (DOT) for 12 weeks (known as the 3HP regimen). This regimen has shown lower toxicity, better adherence and equivalent efficacy\^7-12. INH + Rifapentine (3HP) is not currently used widely as DOT is resource intensive. The investigators hypothesize that if providers use the calculator (TSTin3d.com) to firstly determine risk and then select the once weekly DOT for the TBhi group (12 doses total); the investigators can ensure that the TBhi group completes treatment. Complete treatment of the TBhi group will have the highest impact in decreasing the community burden of TB disease. The investigators propose the first US study to prospectively test the efficacy of an approach which 1) defines the TBhi group using TSTin3d.com and 2) ensures treatment completion in the TBhi group with weekly with video-based DOT (vDOT) with 3HP. Most patients nowadays have access to a smartphone with video capabilities. A HIPAA approved video application (Zoom) is already available through the Missouri Telehealth Network and can be used by the patient to interface with the TB clinic nurse over a smartphone. The investigators approach removes the need for the patients in the TBhi group to be physically present in the TB clinic. All patients identified in the TBhi group can thus be safely provided vDOT. The investigators pilot study has important implications for improving care and patient treatment outcomes as it will identify the "high risk" subjects with latent TB using tstin3d.com (Table 1), \[a validated online calculator that combines TST or interferon Gamma Release Assay (IGRA) screening results with clinical information obtained from the patient, to generate an individual's cumulative risk of developing active TB disease, up to age 80\^11\]. The investigators will then ensure that patients complete therapy under direct observation by a nurse using video based Directly Observed Therapy (vDOT). vDOT also eliminates the need for the patient to physically visit the clinic. All patients need is access to a smartphone with video capabilities. HIPAA approved video based applications are already available for vDOT and has already been implemented successfully.\^13

All of the drug options listed are standard of care currently in the US. It is currently not standard of care to use a scoring system like tstin3d.com to assess risk. There are certain risk factors like having HIV or being on immunosuppression that physicians routinely ask about but most physicians do not do a quantitative risk assessment. Treatment choices are usually based on convenience and concern for side effects but the most common regimen is daily INH for 6 months or 9 months.