INH monotherapy remains the mainstay of LTBI treatment, and adherence will continue to be a significant concern due to the long duration of therapy. Four months of rifampin is an alternate regimen for LTBI that is of shorter duration, has higher patient adherence than 9 months of INH [16, 17], and is likely more cost-effective . However, efficacy studies of rifampin versus INH are limited . Recently, a 3-month regimen of INH and rifapentine once weekly with DOT had very high patient adherence and similar efficacy as 6 or 9 months of INH [20, 21] in both HIV positive and negative patients. However, this regimen is not recommended for young children, HIV patients on antiretroviral therapy, or pregnant women . The medications alone are also 16 times more expensive than INH and although the regimen may be cost-effective or cost-saving at the societal level , it could be difficult in resource-limited settings.
Our study demonstrates that house calls may be an effective method to increase INH treatment adherence to the U.S. national target of 85%. Several strategies to improve treatment adherence have been examined in the past. These have included the use of cultural case-management, education, peer support, financial incentives, direct observed therapy (DOT), and active tracking of patients at high risk of failing to complete treatment [6, 24]. Some of the strategies reported, such as coupling DOT with methadone treatment , are very specific for the intended patient cohort and are less useful in other populations. Non-physician health workers such as pharmacists  or case-manager nurses [25, 26] have also been found effective in following LTBI patients. However all of the interventions studied to date have been clinic-based. House calls to LTBI patients constitute a method that could be applied across many types of patient populations.
One of the limitations of the study was the non-randomized method of assigning patients to receive either house calls or clinic follow-up. The assignment reflected current practice in our clinic and relied on the experience and discretion of the physician and nurse practitioner. It is clear from the different distribution of patient characteristics (Table 1) that clinicians considered the patient’s age, risk of failing to complete treatment, and risk of progression to active tuberculosis when choosing the type of follow-up, and this may have introduced bias or confounding into the study. For example, it is possible that TB contacts are more likely to complete treatment because of patients’ perception of risk, and these patients were also more likely to be assigned home follow-up, particularly because the index case could also be receiving DOT at home. Arguing against this was the finding that TB contacts and routine TST+ patients had similar completion rates within each type of follow-up (Table 2). For example, both TB contacts and TST+ patients from screening had 77% completion with clinic follow-up versus 90% with house calls. Instead, awareness of insufficient resources and staffing might have biased physicians into assigning fewer high-risk patients for home follow-up than they might have otherwise. It was also our practice to refer high-risk patients who missed three clinic appointments to have home follow-up, thereby biasing the home follow-up group with patients more likely to fail treatment completion. Therefore, it is also possible that the true effect of house calls on INH adherence was attenuated. Because patient characteristics between the groups were different, we made an effort to address possible confounders with multivariate analysis. We recognize that residual confounding may remain. For example, there were more patients with abnormal liver enzymes in the clinic follow-up group. This could be explained by a tendency to keep patients with comorbidities in the clinic or a lower threshold for clinic physicians to elicit symptoms and test for liver abnormalities that might otherwise have gone undetected. We acknowledge these limitations of our study. A randomized clinical trial would be helpful in validating home follow-up as a way to increase INH treatment adherence, but might never be funded.
When considering the impact of house calls to follow LTBI patients, the added expense of this approach needs to be measured. The true cost of home-based follow-up in our county is difficult to quantify because both community health workers and public health nurses had other clinical responsibilities and we do not know the exact fraction of time that these health workers specifically spent on house calls. An assessment of cost would need to take into account the time saved by the staff normally involved in the care of LTBI patients in the standard clinic-based follow-up. Several other parameters also need to be evaluated. For example, similar to other TB clinics, we require our patients to return monthly to the clinic for symptom review and assessment of compliance  unless they are followed at home. Although these monthly clinic visits are effective in reducing the incidence of severe INH-related hepatitis , they may be too burdensome on the patient and negatively affect INH adherence. It is possible that only one component of the house calls, such as medication delivery via health workers, is sufficient. Until the shorter, alternate treatment regimens for LTBI become more affordable and widely available, the strategy presented here of home-based follow-up of patients on INH, and the associated cost variables, merit further exploration and study.