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Clinical Investigations: TUBERCULOSIS |

Short-Course Rifamycin and Pyrazinamide Treatment for Latent Tuberculosis Infection in Patients With HIV Infection*: The 2-Year Experience of a Comprehensive Community-Based Program in Broward County, Florida FREE TO VIEW

Masahiro Narita, MD; Michael Kellman, MPH; Diana L. Franchini, MD; Marie E. McMillan, RN; Elena S. Hollender, MD; David Ashkin, MD, FCCP
Author and Funding Information

*From the Broward County Health Department (Mr. Kellman, Dr. Franchini, and Ms. McMillan), Fort Lauderdale; A.G. Holley State Tuberculosis Hospital (Dr. Hollender), Lantana; Florida Department of Health, Bureau of Tuberculosis and Refugee Health (Dr. Ashkin), Tallahassee; and Division of Pulmonary and Critical Care Medicine (Dr. Narita), University of Miami School of Medicine, Miami, FL.

Correspondence to: David Ashkin, MD, FCCP, Florida Tuberculosis Controller, Medical Executive Director, A.G. Holley State Tuberculosis Hospital, 1199 West Lantana Rd, Lantana, FL 33462; e-mail: David_Ashkin@doh.state.fl.us



Chest. 2002;122(4):1292-1298. doi:10.1378/chest.122.4.1292
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Published online

Objectives: To determine the completion rate and tolerability of short-course rifamycin and pyrazinamide treatment of latent tuberculosis infection (LTBI) in HIV-infected patients through a comprehensive community-based program.

Design: Prospective cohort, with comparison to a historical control group.

Patients: Of 3,118 patients with HIV infection screened for LTBI between February 1999 and March 2001, 135 patients were placed on rifamycin/pyrazinamide for 2 months under directly observed therapy and were compared to a historical group comprised of 93 HIV-infected patients who were placed on self-administered treatment of isoniazid for 12 months between 1996 and 1998.

Results: Of 135 patients receiving rifamycin/pyrazinamide, 124 patients (92%) completed treatment; 5 patients had to discontinue treatment due to side effects (allergic skin reactions [n = 4], hepatitis [n = 1]). The completion rate of the historical group who received isoniazid therapy was 61% (57 of 93 patients; p < 0.001); none of those who received isoniazid experienced significant side effects.

Conclusion: In our experience, a comprehensive, community-based program of rifamycin/pyrazinamide for LTBI achieved significantly higher adherence than that of traditional isoniazid therapy, and thus may provide improved tuberculosis prevention in a community with high prevalence of HIV-infected patients.

HIV-infected patients with positive tuberculin skin test (TST) findings have a 200 to 800 times greater chance of acquiring tuberculosis, when compared to the overall US population.1It is imperative to provide treatment for latent tuberculosis infection (LTBI) in HIV-infected patients in order to prevent active tuberculosis disease, thus reducing morbidity and mortality, as well as to forestall the further spread of tuberculosis in this high-risk group. Despite the importance of this public health intervention, it has been difficult to ensure the completion of treatment for LTBI, unless directly observed therapy (DOT) was used for the recommended 12 months of isoniazid therapy.2Recently, short-course treatment for LTBI utilizing 2 to 3 months of rifampin and pyrazinamide has been shown to be effective in HIV-infected individuals. Daily therapy with rifampin/pyrazinamide for 2 months was shown to be as effective as 12 months of isoniazid therapy.3In a study by Halsey et al,4twice-weekly rifampin/pyrazinamide for 2 months was shown to be at least as effective as 6 months of twice-weekly isoniazid therapy among TST-positive, HIV-infected persons. As 6 months of isoniazid has been suggested to be less effective for the treatment of LTBI as compared to 9-month or 12-month isoniazid regimens, and no study has been published to date comparing twice-weekly rifampin/pyrazinamide to 9 months or 12 months of isoniazid, it has been suggested that the twice-weekly regimen of rifampin/pyrazinamide be offered when the preferred or alternative regimens cannot be administered (a category C recommendation).5 Data for the use of rifabutin is less available, although rifabutin can be substituted for rifampin in the treatment of active tuberculosis.1

Given the public health importance of ensuring the completion of LTBI therapy in HIV-infected individuals, DOT may be the most effective method of administration to accomplish this goal. Unfortunately, many public health departments do not have the resources necessary to provide LTBI therapy with isoniazid, even twice weekly for 9 months. Twice-weekly rifamycin/pyrazinamide for 2 months might be effectively implemented with limited resources in a community. It is theoretically possible that the overall benefit, and prevention of tuberculosis in a community could be improved due to higher rates of completion anticipated by DOT, even if that regimen in any one individual was not as successful as INH for 9 months to prevent tuberculosis disease. This study was undertaken to evaluate the completion rate and tolerability of the short-course, twice-weekly rifamycin/pyrazinamide regimen in a community setting. We describe our experience in a prospective cohort of HIV-infected patients with LTBI, utilizing this regimen in Broward County, Florida.

A network of community HIV care providers was established by the Broward County Health Department (BCHD), consisting of the BCHD Tuberculosis Control Program, the BCHD HIV Program, and selected community HIV clinics in Broward County, Florida. All HIV-infected patients seen by these health-care providers from February 1, 1999, to March 31, 2001, were evaluated for LTBI and active tuberculosis disease. Specially trained community outreach staff of the BCHD visited each clinic on a regular basis and performed chart reviews to identify those patients due for their annual tuberculosis screening.

Once an eligible patient was identified, a “colorful” reminder was placed on the medical records to notify the staff that a tuberculosis evaluation should be performed at the next visit. The clinic service providers were responsible for performing a tuberculosis evaluation, which included a symptom screen and TST. If no symptoms compatible with active tuberculosis disease were elicited, then a TST utilizing the Mantoux method (0.1 mL of 5 tuberculin units of Tubersol [Pasteur Merieux Connaught; Swiftwater, PA] intradermal injection) was applied. If symptoms compatible with active tuberculosis disease were present, a workup for tuberculosis disease was initiated. Patients who had TSTs placed were requested to return to the clinic within 48 to 72 h after placement for a reading of the test. If patients failed to return for TST readings, the outreach staff conducted home visits to perform these readings. The results were reported back to the respective HIV service providers for further evaluation. Patients with a TST induration ≥ 5 mm were considered to have a positive reaction. All TST-positive patients underwent chest radiography.

Therapy for LTBI was initiated with 2 months of twice-weekly rifamycin/pyrazinamide by DOT when one of the following criteria for the treatment of LTBI was present: (1) the patient was a close contact to an infectious tuberculosis disease case, or (2) the patient had a current or previously documented positive TST result (induration of ≥ 5 mm) with no history of adequate treatment for LTBI. This study was approved by the State of Florida, Department of Health’s Review Council for Human Subjects, and written consents were obtained from participants prior to the initiation of treatment of LTBI.

The regimen of rifampin/pyrazinamide was ordered when the patient was not receiving a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor: 600 mg of rifampin with pyrazinamide 50 mg/kg of body weight (maximum 4 g) administered twice weekly by DOT. If the patient was receiving a protease inhibitor or nonnucleoside reverse transcriptase inhibitor, then 300 mg of rifabutin, with pyrazinamide 50 mg/kg of body weight (maximum 4 g) was administered twice weekly by DOT (exception: 450 mg of rifabutin was concurrently administered with efavirenz). Serum glutamate oxaloacetate transaminase (SGOT) was obtained at baseline and at 4 weeks into treatment with rifamycin/pyrazinamide therapy. At baseline, HIV antibodies were tested by enzyme-linked immunosorbent assay, with a confirmatory Western blot assay. CD4 cell counts were measured by flow cytometry, and HIV-RNA levels were quantified by polymerase chain reaction (reverse transcriptase-polymerase chain reaction assay by Broward General Medical Center, Department of Laboratory Services).

The community outreach staff workers provided the twice-weekly DOT until completion of therapy. Symptoms of adverse reactions were elicited and, if present, documented and immediately related to the respective clinic staff. Evidence of nonadherence was immediately reported to the respective HIV service provider. In addition, after therapy was completed, the community outreach staff workers performed evaluations for development of active tuberculosis every 3 months for up to 2 years; if there was development of new tuberculosis symptoms, sputum collection and radiographic evaluation were done.

Treatment completion rate was defined as follows: (No. of patients who completed LTBI treatment) ÷ (No. of patients who were initiated on treatment for LTBI). If the TST results were negative, a repeat TST was performed annually (except for one center where a TST was performed every 6 months).

In order to compare the treatment completion rates between rifamycin/pyrazinamide and isoniazid therapy, a retrospective chart review was performed on HIV-infected individuals who were evaluated and placed on 12 months of self-administered isoniazid therapy for LTBI treatment by the same network of community HIV-care providers and BCHD Tuberculosis Control Program from January 1, 1996, to December 31, 1998. This group of patients was considered the “historical” isoniazid group and received a baseline SGOT and subsequent monthly clinical evaluations for symptoms of disease or adverse reactions. If symptoms of hepatitis developed, then repeat SGOT was performed. In this group, a patient was considered to have completed therapy if the individual picked up the monthly supply of isoniazid for a total of 12 months. This group also was followed up by the community outreach staff workers for development of active tuberculosis every 3 months for up to 2 years after completion of treatment; if there was development of new tuberculosis symptoms, sputum collection and radiographic evaluation were done.

Statistical analysis was performed using the Student t test for continuous variables, Mann-Whitney rank sum test for nonparametric variables, and χ2 test, or the Fisher exact test if appropriate, for categorical variables. A p value of < 0.05 was considered to indicate statistical significance; all tests were two tailed.

A total of 3,118 patients with HIV infection were evaluated between February 1999 and March 2001. Of these 3,118 patients, 2,334 patients (75%) were born in the United States and 784 (25%) were foreign born: Haiti (n = 384), Jamaica (n = 74), Venezuela (n = 42), Cuba (n = 28), Columbia (n = 19), and other countries (n = 237). Four hundred six patients (13%) had a history of drug abuse, 65 patients (2%) had a history of homelessness, 196 patients (6%) had a history of alcohol abuse, and 73 patients (2%) had a history of incarceration. Patients with a history of a previously positive TST finding and adequate treatment for LTBI (n = 153), or prior tuberculosis disease with adequate treatment (n = 131), were excluded from the study. Moreover, active tuberculosis disease was diagnosed in 24 of the 3,118 screened patients (0.8%) during the initial assessment. Of the 2,834 eligible patients, 589 patients (21%) were unable to have a TST applied. In addition, the clinical records of 13 patients had restricted access and further data were not available. Of the 2,232 patients who received a TST, 105 patients (5%) did not have their TST results read. Of the 2,127 patients who had TST results read, 178 patients (8.4%) had a positive TST finding and 1,949 patients had a negative TST finding (Table 1 ).

Of the 178 patients with a positive TST finding, 34 patients (19%; p < 0.001 compared to 206 of 1,949 patients in the TST-negative group) had a history of drug abuse, 15 patients (8%; p < 0.001 compared to 32 of 1,949 patients in the TST-negative group) had a history of homelessness, 15 patients (8%; p = 0.25 compared to 116 of 1,949 patients in the TST-negative group) had a history of alcohol abuse, and 11 patients (6%; p = 0.97 compared to 35 of 1,949 patients in the TST-negative group) had a history of incarceration.

Of the 178 patients with a positive TST finding, two patients (1.1%) were found to have active tuberculosis disease, and another individual was suspected to have tuberculosis disease. Two other patients moved out of Broward County prior to the intiation of treatment. Three additional patients with negative TST findings, but identified as a recent close contact to an active tuberculosis case, were eligible for treatment of LTBI. Of the 176 patients eligible for treatment of LTBI, 160 patients (91%) were started on medications, 3 patients refused treatment, and 13 patients started treatment after closure of the study.

There were 94 patients receiving twice-weekly rifabutin/pyrazinamide and 41 patients receiving twice-weekly rifampin/pyrazinamide. Twenty-four patients were started on daily isoniazid and 1 patient was started on twice-weekly isoniazid therapy due to preference of the treating physician (Table 2 ). Of the 94 patients receiving twice-weekly rifabutin/pyrazinamide, side effects developed in 9 patients (10%): pruritus (n = 5), rash (n = 2), elevated liver enzymes (n = 1), and headache (n = 1). Only two patients (2%; one patient with allergic skin reaction [nonsevere] and one patient with asymptomatic hepatitis [SGOT 316 IU/L, serum glutamate-pyruvate transaminase 601 IU/L and total bilirubin 1.0 mg/dL with negative viral hepatitis serology]) had to have the therapy discontinued; both were switched to isoniazid therapy and completed treatment of LTBI without further problems. Eighty-nine patients (95%) completed the rifabutin/pyrazinamide treatment, and 3 patients (3%) were nonadherent. Of the 41 patients receiving twice-weekly rifampin/pyrazinamide, allergic skin reactions developed in 3 patients (nonsevere), and they were switched to isoniazid therapy and completed the treatment of LTBI without further problems. Thirty-seven patients (90%) completed rifampin/pyrazinamide, and 1 patient was nonadherent. The characteristics of the 135 patients receiving rifamycin/pyrazinamide are summarized in Table 3 .

As of March 1, 2002, the patients who completed treatment for LTBI have been followed up for 106 ± 30 weeks (mean ± SD; median, 107 weeks; range, 30 to 152 weeks). One hundred twelve of 135 patients (83%) were followed up for > 12 months, and 59 of these 112 patients were followed up for > 24 months. Only one patient was found to have culture-positive pulmonary tuberculosis disease during follow-up (6 months after the completion of rifabutin/pyrazinamide).

Reviewing the previous experience of isoniazid therapy for LTBI between 1996 and 1998, 93 HIV-infected patients were placed on self-administered isoniazid therapy for 12 months (the historical isoniazid group; 91 patients with positive TST findings and 2 patients with close contacts to infectious tuberculosis disease). The characteristics of these 93 patients are summarized in Table 3. Of the 93 patients, 57 patients (61%) completed the treatment, 31 patients (33%) discontinued therapy themselves before completion (13 patients received isoniazid for 1 month, 2 patients for 2 months, 9 patients for 3 months, 1 patient for 5 months, 3 patients for 6 months, and 3 patients for 9 months), 4 patients (5%) were unavailable for to follow-up, and 1 patient (1%) moved out of Broward County. The completion rate of the historical isoniazid group was significantly lower compared to the rifamycin/pyrazinamide group (p < 0.001). The characteristics of the two groups (historical isoniazid group vs rifamycin/pyrazinamide group) were not significantly different except in age. None of those receiving isoniazid therapy had to discontinue treatment due to adverse reactions, and none were subsequently found to have tuberculosis disease (median follow-up, 36 months; range, 15 to 59 months).

At 80,416, Florida has the third highest number of HIV-infected individuals in the United States.6Broward County, Florida, has a population of 1.6 million and includes a large urban city, Fort Lauderdale.7 In 2000, the rate of HIV in Fort Lauderdale was 53 per 100,000 populations, the third highest rate in the nation among large metropolitan cities.6Broward County is home to many recent immigrants from the Caribbean and Latin America; 16.7% of residents in Broward County are Hispanic.7Many areas in the Caribbean and Latin America have been identified as regions of the world with a high prevalence of tuberculosis and HIV.89 Due to cultural and ethnic barriers, tuberculosis control among minority groups with poor access to health care has been a concern, especially when there is co-infection with HIV. In fact, in our study, 24 patients (0.8% of the screened patients) were found to have active tuberculosis disease, which was discovered due to the heightened surveillance by this project. Our study focused on those people with the highest risk of developing tuberculosis disease, those with HIV infection, who received treatment for LTBI by the Broward County Tuberculosis Control Program.

The Centers for Disease Control and Prevention recently updated the guidelines for the treatment of LTBI and recommended 9 months of isoniazid for LTBI to optimize the probability against developing tuberculosis disease. Twice-weekly isoniazid by DOT for 9 months is an option, but many public health departments do not have the resources necessary to provide LTBI patients with DOT twice a week for 9 months. In the past, utilizing self-administered isoniazid treatment for 12 months, 61% of patients completed this regimen in Broward County. A report from a community-based setting in an Atlanta urban area showed a 21% isoniazid treatment completion rate, though this was not an HIV-targeted study.10 It has been hoped that adherence to LTBI therapy may improve with a shorter duration of therapy.

It was previously thought that part of the poor completion rates of LTBI treatment in our program was due to the lack of resources available to perform DOT for the recommended 9 to 12 months. It was determined, however, that our program did have the resources (including personnel) to offer DOT twice weekly for 2 months. Given the importance of this intervention and the potential impact on tuberculosis in this population, it was believed that a study was warranted to determine the effectiveness of this regimen. This study looks first at the completion rates and side effect profiles of the short-course rifamycin/pyrazinamide LTBI treatment regimen; 124 of 135 patients (92%) completed 2 months of rifamycin/pyrazinamide twice weekly by DOT in a community-based setting, a significant improvement over previous completion rates.

It has been suggested that a twice-weekly regimen of rifamycin/pyrazinamide for 2 months may not be as effective as 9 months of isoniazid therapy for LTBI; however, this is based on a lack of adequate data.5 It has been our experience, as well as that of others, that good adherence to LTBI treatment is often difficult to attain and thus a regimen that enhances compliance may improve overall programmatic efficacy. For example, if the efficacy of 9 months of isoniazid is 92% and the completion rate of this regimen is 60% (as attained by our program and others5), the rate of tuberculosis disease in TST-positive, HIV-infected individuals would be 3.58% (assuming 8% of HIV-infected, TST-positive individuals will have active tuberculosis disease develop per year if left untreated11 and the efficacy of incomplete treatment being nil). However, if the efficacy of twice-weekly rifamycin/pyrazinamide is assumed to be even as low as 70% but its completion rate is 90%, the rate of tuberculosis disease in TST-positive, HIV-infected individuals would be 2.96% (lower than would be expected from 9 months of isoniazid therapy) [Table 4] . Although this is a simplified scheme, the difference between the two regimens may become even more significant when true adherence to self-administered isoniazid for 9 months is taken into consideration.

The positive outcome of this prospective study was believed to be due principally to two factors: the working partnership between the BCHD Tuberculosis Control Program and publicly funded HIV clinics, and the effectiveness of the community outreach workers. The BCHD Tuberculosis Control Program developed a unique network of partnerships with publicly funded HIV clinics in areas where HIV infection and tuberculosis high-risk groups are highly prevalent. This longstanding partnership has been one that has allowed these health-care centers not only to provide HIV services but also a variety of other health-care services to a large, diverse community with multiple needs. One agency alone would not have had the ability nor the resources to accomplish this. The effectiveness of community outreach staff is indicated by the fact that 95% of patients who had a TST placed subsequently had it read. Another strength of the outreach staff was that they culturally, ethnically, and linguistically mirrored the diverse populations that they served.

There are several limitations to our study. First, the treatment of LTBI was not randomized; thus, there may have been a bias that physicians prejudged whether individuals would be nonadherent with the LTBI treatment and those deemed nonadherent were assigned to self-administered isoniazid therapy in order to minimize potentially wasted effort in providing DOT. This would have raised the completion rate of rifamycin/pyrazinamide by eliminating nonadherent individuals. Second, for the comparison between rifamycin/pyrazinamide and isoniazid therapy, a historical group was used. A significant bias may have been involved, such as different patient attitudes toward treatment (eg, more informed/motivated patients in the former group) and difference in the intensity of follow-up by the tuberculosis control program. Moreover, the historical isoniazid group had to receive 12 months of isoniazid in order to complete the treatment, which is longer than the currently recommended 9 months of isoniazid for LTBI in HIV-infected individuals.

Nonetheless, we found that the regimen of rifamycin/pyrazinamide, given by DOT, had a high completion rate and was well tolerated. Four patients (3%) stopped the rifamycin/pyrazinamide treatment due to allergic skin reactions. Only 1 of 135 patients had to discontinue rifamycin/pyrazinamide due to elevated liver enzymes, and none of the patients had severe hepatitis. This may be due, in part, to the outreach staff’s close monitoring of symptoms, as well as repeated following of hepatic enzymes. This finding was consistent with the two trials (conducted in Zambia12 and Haiti4) of intermittent dosing of rifampin/pyrazinamide in HIV-infected patients, which showed a low incidence of elevated liver enzymes at 1 of 360 (0.3%) and 1 to 3% (no participants had to discontinue medications), respectively. The daily rifampin/pyrazinamide regimen was reported to have a rate of abnormal liver function testing and hepatitis of 1.4% and 0.8%, respectively.3 This low incidence of drug-induced hepatitis was seen in the rifamycin/pyrazinamide group, although there has been a report of higher incidences of drug-induced hepatitis in HIV infected tuberculosis patients receiving tuberculosis medications including isoniazid, rifampin, and pyrazinamide.13Several cases of fatal/near-fatal hepatitis triggered by rifampin/pyrazinamide have been reported,1415 but our results and those of others16 are encouraging in the low incidence of drug-induced hepatitis that was found. It is worth noting that none of those patients receiving isoniazid therapy had to discontinue treatment due to adverse reactions.

Of the 96 patients who completed therapy with rifamycin/pyrazinamide and were followed up for > 12 months, 1 patient subsequently had culture-positive tuberculosis develop. It is clear that rifamycin/pyrazinamide twice-weekly regimen does not provide 100% prevention of active tuberculosis disease, though the one case of subsequent tuberculosis disease could have resulted from new transmission and re-infection.

This study shows that twice-weekly rifamycin/pyrazinamide by DOT for the treatment of LTBI is practical and well tolerated in a community setting of HIV-infected patients, and has a high completion rate in this crucial population. Public health programs may be able to apply this strategy to their high-risk, HIV-infected populations, thereby improving tuberculosis control. When utilizing short-course, twice-weekly rifamycin/pyrazinamide treatment in community settings, public health departments should place a priority on developing integral working relationships with community outreach programs in order to optimize resources and health-care outcomes and afford close monitoring of the patient.

Abbreviations: BCHD = Broward County Health Department; DOT = directly observed treatment; LTBI = latent tuberculosis infection; SGOT = serum glutamate oxaloacetate transaminase; TST = tuberculin skin test

A preliminary report of this work was presented at the 8th Conference on Retroviruses and Opportunistic Infections, Chicago, IL, February 4–8, 2001.

Funding for the outreach staff was made possible through a cooperative relationship between the local chapter of the American Lung Association and the Florida Department of Health Tuberculosis Control Program, and local Ryan White title III grant funds to the Broward County Health Department Tuberculosis Program.

Table Graphic Jump Location
Table 1. Summary of HIV-infected Patients Screened
Table Graphic Jump Location
Table 2. Treatment of LTBI in HIV-Infected Patients in Broward County, 1999–2001
Table Graphic Jump Location
Table 3. Patient Characteristics: Rifamycin/Pyrazinamide vs Historical Isoniazid Group*
* 

Data are presented as mean ± SD, No., or No. (%).

Table Graphic Jump Location
Table 4. Theoretical Protection in 100 TST-positive, HIV-infected Patients

The authors thank Heather Duncan from the Bureau of Tuberculosis Control and Refugee Health, Florida Department of Health, for technical assistance and critical review, and Nalinie Samlal from the American Lung Association of South Florida, Inc, for assistance in data collection.

. Centers for Disease Control and Prevention (1998) Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations.MMWR Morb Mortal Wkly Rep47(RR-20),1-58
 
American Thoracic Society/Centers for Disease Control and Prevention. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society.Am J Respir Crit Care Med1994;149,1359-1374. [PubMed]
 
Gordin, F, Chaisson, RE, Matts, JP, et al Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.JAMA2000;283,1445-1450. [PubMed] [CrossRef]
 
Halsey, NA, Coberly, JS, Desormeaux, J, et al Randomised trial of isoniazid vs rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.Lancet1998;351,786-792. [PubMed]
 
Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society.MMWR Morb Mortal Wkly Rep2000;49(RR-6),1-51
 
Centers for Disease Control and Prevention. HIV/AIDS Surveill Report 2001; 12:8–10.
 
2000 census. Available at: www.census.gov. Accessed September 17, 2002.
 
UNAIDS. Report on the global HIV/AIDS epidemic, 2000. Available at: www.unaids.org/epidemic_update/report_july02/index.html. Accessed September 19, 2002.
 
Dye, C, Scheele, S, Dolin, P, et al Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance Monitoring Project.JAMA1999;282,677-686. [PubMed]
 
Bock, NN, Metzger, BS, Tapia, JR, et al A tuberculin screening and isoniazid preventive therapy program in an inner-city population.Am J Respir Crit Care Med1999;159,295-300. [PubMed]
 
Selwyn, PA, Hartel, D, Lewis, VA, et al A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection.N Engl J Med1989;320,545-550. [PubMed]
 
Mwinga, A, Hosp, M, Godfrey-Faussett, P, et al Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.AIDS1998;12,2447-2457. [PubMed]
 
Ungo, JR, Jones, D, Ashkin, D, et al Antituberculosis drug-induced hepatotoxicity: the role of hepatitis C virus and the human immunodeficiency virus.Am J Respir Crit Care Med1998;157,1871-1876. [PubMed]
 
Centers for Disease Control, and Prevention. Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection–New York and Georgia, 2000.MMWR Morb Mortal Wkly Rep2001;50,289-291. [PubMed]
 
Centers for Disease Control and Prevention update. Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations—United States, 2001.MMWR Morb Mortal Wkly Rep2001;50,733-735. [PubMed]
 
Bock, NN, Rogers, T, Tapia, JR, et al Acceptability of short-course rifampin and pyrazinamide treatment of latent tuberculosis infection among jail inmates.Chest2001;119,833-837. [PubMed]
 

Figures

Tables

Table Graphic Jump Location
Table 1. Summary of HIV-infected Patients Screened
Table Graphic Jump Location
Table 2. Treatment of LTBI in HIV-Infected Patients in Broward County, 1999–2001
Table Graphic Jump Location
Table 3. Patient Characteristics: Rifamycin/Pyrazinamide vs Historical Isoniazid Group*
* 

Data are presented as mean ± SD, No., or No. (%).

Table Graphic Jump Location
Table 4. Theoretical Protection in 100 TST-positive, HIV-infected Patients

References

. Centers for Disease Control and Prevention (1998) Prevention and treatment of tuberculosis among patients infected with human immunodeficiency virus: principles of therapy and revised recommendations.MMWR Morb Mortal Wkly Rep47(RR-20),1-58
 
American Thoracic Society/Centers for Disease Control and Prevention. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society.Am J Respir Crit Care Med1994;149,1359-1374. [PubMed]
 
Gordin, F, Chaisson, RE, Matts, JP, et al Rifampin and pyrazinamide vs isoniazid for prevention of tuberculosis in HIV-infected persons: an international randomized trial. Terry Beirn Community Programs for Clinical Research on AIDS, the Adult AIDS Clinical Trials Group, the Pan American Health Organization, and the Centers for Disease Control and Prevention Study Group.JAMA2000;283,1445-1450. [PubMed] [CrossRef]
 
Halsey, NA, Coberly, JS, Desormeaux, J, et al Randomised trial of isoniazid vs rifampicin and pyrazinamide for prevention of tuberculosis in HIV-1 infection.Lancet1998;351,786-792. [PubMed]
 
Centers for Disease Control and Prevention. Targeted tuberculin testing and treatment of latent tuberculosis infection. American Thoracic Society.MMWR Morb Mortal Wkly Rep2000;49(RR-6),1-51
 
Centers for Disease Control and Prevention. HIV/AIDS Surveill Report 2001; 12:8–10.
 
2000 census. Available at: www.census.gov. Accessed September 17, 2002.
 
UNAIDS. Report on the global HIV/AIDS epidemic, 2000. Available at: www.unaids.org/epidemic_update/report_july02/index.html. Accessed September 19, 2002.
 
Dye, C, Scheele, S, Dolin, P, et al Global burden of tuberculosis: estimated incidence, prevalence, and mortality by country. WHO Global Surveillance Monitoring Project.JAMA1999;282,677-686. [PubMed]
 
Bock, NN, Metzger, BS, Tapia, JR, et al A tuberculin screening and isoniazid preventive therapy program in an inner-city population.Am J Respir Crit Care Med1999;159,295-300. [PubMed]
 
Selwyn, PA, Hartel, D, Lewis, VA, et al A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection.N Engl J Med1989;320,545-550. [PubMed]
 
Mwinga, A, Hosp, M, Godfrey-Faussett, P, et al Twice weekly tuberculosis preventive therapy in HIV infection in Zambia.AIDS1998;12,2447-2457. [PubMed]
 
Ungo, JR, Jones, D, Ashkin, D, et al Antituberculosis drug-induced hepatotoxicity: the role of hepatitis C virus and the human immunodeficiency virus.Am J Respir Crit Care Med1998;157,1871-1876. [PubMed]
 
Centers for Disease Control, and Prevention. Fatal and severe hepatitis associated with rifampin and pyrazinamide for the treatment of latent tuberculosis infection–New York and Georgia, 2000.MMWR Morb Mortal Wkly Rep2001;50,289-291. [PubMed]
 
Centers for Disease Control and Prevention update. Fatal and severe liver injuries associated with rifampin and pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations—United States, 2001.MMWR Morb Mortal Wkly Rep2001;50,733-735. [PubMed]
 
Bock, NN, Rogers, T, Tapia, JR, et al Acceptability of short-course rifampin and pyrazinamide treatment of latent tuberculosis infection among jail inmates.Chest2001;119,833-837. [PubMed]
 
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