The U.S. Centers for Disease Control and Prevention Institutional Review Board B and the California Health and Human Services Agency's Committee for the Protection of Human Subjects (CPHS) and the Los Angeles County Public Health Institutional Review Board and each of four clinics Institutional Review Boards (IRBs) approved the study and granted a waiver of patient informed consent and patient authorization for the clinic record reviews. (All three criteria for such a waiver were satisfied: 1) the use or disclosure of protected health information (PHI) involves no more than a minimal risk to the privacy of individuals, 2) the research could not practicably be conducted without the waiver, and 3) the research could not be conducted without access to and use of the PHI.) All institutional review boards that approved the study also approved the following approach. All participating clinic staff interviewed gave written informed consent. However, to eliminate the possibility of identification of the interviewee through linkage of consent form signatures, a waiver of documentation of informed consent under 45 CFR 46.117(c) enabled the use of a check box rather than a signature to indicate consent was obtained; the interviewer then signed the consent form.

Two U.S. Metropolitan Statistical Areas (MSA) with elevated HIV and TB prevalence were selected: New York City and Los Angeles. The Ryan White HIV/AIDS Program (RWP) of the Health Resources and Services Administration (HRSA) addresses the health needs of low-income PLWH by funding primary HIV care (http://hab.hrsa.gov). Two RWP Part C-funded HIV clinics from each MSA having at least 450 patients annually participated. All four clinics served predominantly racial/ethnic minority populations: two were hospital-based, one was a private community clinic, and one was a health department clinic. All clinics participated in the HRSA quality assurance program [9].

Study staff abstracted medical records of a random sample of 600 HIV-infected patients having at least one clinic visit in 2009 (150 consecutive patients from each clinic). We examined patient characteristics and TB services outcomes (i.e., frequency having TBI tests, TBI treatment, TB symptom screening, chest radiography, and TB disease) during 2008–2010. We concluded data collection on December 31, 2010. We assumed that chest radiographs were used for TB evaluation. We used multivariable logistic regression, with a backwards selection strategy, to identify patient characteristics that were independently associated with TBI testing and chest radiography. Variables assessed in the TBI testing and chest radiography models included those associated with characteristics in Table 1. We applied a threshold p-value of 0.05 to keep the variable in the model.

We weighted each observation of patient-level data by the probability of selection at the clinic (inverse of the total clinic population divided by 150). We estimated the annual rates of TBI testing, and chest radiography by dividing the total number of tests by the number of person-years at the clinic. To estimate the TB disease rate, we first calculated the weighted rate per year; then selected the median rate and estimated the non-parametric 95% confidence interval. SAS version 9.2 (SAS Institute Inc., Cary, North Carolina) was used for statistical analyses.

We collected and abstracted written clinic policies, relevant to TBI and TB testing, diagnosis, and treatment; and, observed clinic environment and encounters with patients. Clinic directors (N = 4) and TB program directors (N = 3) identified their staff who had sufficient program knowledge to be key informants for the study. Trained study staff conducted face-to-face key informant interviews using a semi-structured instrument, and verified responses by audio recordings. We reviewed and used data from written policies, clinic observations, and key informant interviews with clinic and TB program staff to describe practices of TBI testing, TBI treatment, TB disease evaluation, and linkages with TB programs.

We present characteristics of the 600 patients in Table 1. Two-thirds of study patients had been in care for HIV at their clinic for at least five years. The majority of patients were male (N = 419, 70%), and of black race (N = 281, 47%) or Hispanic ethnicity (N = 246, 41%). Of those with known birth country (N = 415), 157 (38%) were foreign-born, with 97 (62%) born in Mexico. Many patients had risk factors for TB, including history of: non-injection drug use (N = 149, 25%), excess alcohol consumption (N = 63, 11%), injection drug use (N = 57, 10%), incarceration (N = 71, 12%), and homelessness (N = 58, 10%). Only two patients had documented contact with a person with infectious TB. In addition to HIV infection, patients had other risk factors for TB disease: 68 (11%) had diabetes; 21 (4%) had cancer, 18 (3%) were on prolonged corticosteroid therapy, five (1%) had hematologic disease, and five (1%) had end-stage renal disease.

The majority (N = 317, 53%) of patients had a nadir CD4 count of less than 200. While nearly all (N = 573, 96%) had been on HAART at some time during the study period, 22% were known to have started HAART more than once while at the clinic. Patients without history of TBI or TB were eligible for annual TB testing, per study clinic policy (see below). Thus, 500 patients (83%) were eligible for TBI tests in 2008–2010 because they did not have a history of TBI or TB prior to 2008 (Table 1). One hundred patients (17%) had TBI (N = 79) or TB disease (N = 21) prior to 2008.

As shown in Table 2, 393 (79%) of 500 eligible patients were tested with either a TST or IGRA at least once during 2008–2010. Of 393 tested, 20 (5%) patients had positive, 357 (91%) had negative, 14 (4%) had no documented TST results, and two had indeterminate IGRA results. Of the 20 newly diagnosed TST/IGRA-positive patients, 13 (65%) had documented TB symptom screening, and 19 (95%) had documented chest radiography during 2008–2010. Of the 20 patients who tested positive for TBI, 14 (70%) initiated TBI treatment at the clinic (see Figure 1). Three (15%) patients were still on treatment when staff concluded data collection. Excluding the three patients who were still on treatment, only three (27%) of 11 completed treatment (i.e., medical record documented 9 months of INH); two (18%) did not complete; and six (55%) had no documentation of treatment completion. One patient who did not complete treatment was diagnosed with and treated for TB disease (Figure 1).

Of the 357 TST/IGRA-negative patients, 199 (56%) had documented TB symptom screening, and 160 (45%) had documented chest radiography (Table 2). One TST-negative patient was fully evaluated and diagnosed with TB disease. Of the 107 patients not tested for TBI, 62 (58%) had documented TB symptom screening and 57 (53%) had documented chest radiography (Table 2).

Of the 79 patients who had TBI prior to 2008, 44 (56%) had documented TB symptom screening and 67 (85%) had documented chest radiography in 2008–2010. One patient in this group had completed treatment for TBI in 2000, but was diagnosed with TB disease in 2008, after chest radiography and specimen collection. Of the 21 patients with TB disease prior to 2008, 17 (81%) had documented TB symptom screening and 9 (43%) had documented chest radiography in 2008–2010 (Table 2).

Overall, among all 600 patients, 323 (54%) had documentation of chest radiography, and 346 (58%) had documentation of TB symptom screening at least once during 2008–2010. The median individual weighted rate of chest radiography was 0.7 times per year. For the 500 patients eligible for TBI testing, the median individual weighted rate of TST or IGRA testing was 0.7 times per year.

Three patients had TB disease during 2008–2010; the median weighted population rate of TB disease was 117 per 100,000 person years, with a 95% confidence interval of 101–165.

Patient characteristics independently associated with TBI testing included: non-Hispanic ethnicity (adjusted odds ratio (aOR) = 4.9, 95% confidence interval (CI) = 2.6–9.5), receipt of care at a participating clinic in Los Angeles (aOR = 3.1, 95% CI = 1.5–6.4), and employment (aOR = 1.9, 95% CI = 1.0–3.4). Patient characteristics associated with having received a chest radiograph included: female gender (aOR = 2.0, 95% CI = 1.4–3.3); non-black race (aOR = 1.7, 95% CI = 1.3–2.5); and unemployment (aOR = 1.5, 95% CI = 1.1–2.1) (Table 3). Country of birth could not be assessed in the models due to a high frequency (31%) of missing data.

Key informants were interviewed in Los Angeles (n = 12, with 1 from the local TB program) and the New York MSA (n = 8, with 2 from local TB programs). Key informants from each of the four clinics reported that identification and prevention of TB was a high priority activity. However, written clinic policies did not specifically mention TBI testing and treatment, except for Clinic 4 which instructed staff to record annual dates and results of the tests (Table 4). Clinic 2 outlined the roles and responsibilities of clinic staff working with the local TB control program to provide directly observed therapy for patients with TB disease (Table 4). References for clinic policies were reported to be: local or state TB program manuals, national guidance on HIV primary care [10], and national guidelines [3], [11], [12].

Informants from all clinics reported that TST placement and reading, or IGRA testing, and chest radiography, were provided during patients' initial evaluations, i.e., within three months of intake, and annually thereafter. Clinics 1 and 2 reported the use of TSTs only, whereas Clinics 3 and 4 used IGRAs in a small proportion of patients and TSTs in most patients. Clinics 1 and 2 planned to implement IGRAs in the coming year. Informants confirmed that patients with prior TBI or TB disease were to receive an annual chest radiograph to assess potentially active TB disease. All clinics referred patients with positive TSTs/IGRAs for chest radiography and physician evaluation to rule out TB disease prior to initiating TBI treatment. Although all clinics had similar methods to encourage return visits for TST reading, i.e., reminder phone calls and monitoring of return visits, and reviewed TBI test completion monthly or quarterly, only Clinics 1 and 4 partnered with their local TB program to perform systematic monitoring of TBI testing and treatment (Table 4).

Clinic patients with abnormal chest radiographs were referred to a clinic-associated hospital or to the local TB clinic for further assessment and TB treatment, if indicated (Table 4). Each clinic provided continuity of care for patients on anti-TB treatment. To support patients undergoing TB services, clinics provided medical interpreters for non-English-speaking patients, and three clinics displayed or provided TB-specific patient education materials (Table 4).

Although all clinics had access to consultation from their local health department TB program, the extent of the partnership with the TB program varied. Clinics 1 and 4 had the highest TBI test rates and reported the most frequent and routine interactions, including joint monitoring and assessment of TBI testing and treatment (Table 4). Clinic 1 partnered with its local TB program to perform systematic review of completion and outcomes of TBI testing and treatment and Clinic 4 shared and routinely reviewed patient data with its local TB program. Key informants from two of the three TB programs that interfaced with the clinics reported the recent loss of staff that performed partnership activities, e.g., monitoring of TBI testing and treatment of patients at HIV clinics. (Table 4).

In response to an interview question regarding barriers to TBI testing and treatment, key informants from three clinics reported that the follow-up visit required for reading the TST was a barrier for patient retention and completion of TBI testing. According to clinic staff, IGRAs, while desirable, were of limited utility because of their high cost and high frequency of indeterminate results. One key informant stated that barriers for completion of TBI treatment included the perception of a large pill burden, long (9-month) treatment regimen, and, for immigrant patients, language differences and uncertain legal status resulting in reluctance to present for care.

In response to an interview question regarding facilitators to TB testing and treatment, key informants noted the following: TB expertise among staff, having sufficient clinic supplies, use of IGRAs, positive relationships with local TB program staff and review of shared electronic medical records, use of electronic patient records and tracking systems to facilitate annual TBI testing, having staff trained in cultural competency, and the institutional recognition of the importance of TBI testing. Key informants from all clinics reported that TBI testing was an indicator in their HRSA quality management programs.