Important note: Information in this article was accurate in March 2001. The state of the art may have changed since the publication date. | The online version of HEPP News displays the main article only, to view the entire newsletter download the following PDF:
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There is a perilous synergy between HIV and tuberculosis in correctional facilities. Prisoners, who have long been known to have disproportionately high rates of diagnosed TB disease and TB infection,1 (See Figure 1) also have more than 5 times the general population's rate of AIDS, and between 4 and 10 times the general population's rate of HIV infection.2 Crowding, poor ventilation, the high prevalence of HIV among prisoners, and the higher prevalence of TB in the communities from which prisoners are disproportionately drawn can make correctional facilities key sites of amplification for TB transmission. This article will review the interactions between HIV and TB in correctional settings, describe a recent outbreak of TB in a facility where HIV-infected inmates are segregated, and address the treatment of TB in HIV-infected individuals.
During the Spring of 2000, South Carolina reported a significant TB outbreak among HIV-positive prisoners.3 Contemporaneously, the Institute of Medicine released a report on the lamentable state of TB eradication,4 and the CDC released updated guidelines for simultaneous treatment of HIV and TB5 and new guidance on targeted screening and treatment of latent TB infection.6 The South Carolina outbreak serves as a compelling reminder that this emphasis on guidelines and standards for TB in prisons and jails is well justified.
In August 1999, two men who had been housed on the HIV-segregation unit in the Broad River Men's Correctional Institution in Columbia, South Carolina were diagnosed with sputum smear-positive pulmonary tuberculosis.7 The first patient had a previously documented tuberculin skin test reaction of 15 mm in 1984 and two subsequent incomplete attempts at isoniazid prophylaxis. Six weeks before his TB diagnosis, in July 1999, he was admitted to a community hospital with fever, abdominal pain, and cough. The patient's chest radiograph was normal and, despite existing guidelines for the treatment of HIV-infected, PPD positive individuals (See HEPP News March 2000, and Prevention and Treatment of Tuberculosis Among Patients Infected with Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations, MMWR 1998; 47(No. RR-20):1-58), no sputum specimens were obtained for AFB smear and culture. He was not placed in respiratory isolation and was returned to the prison. Six weeks later, in mid-August, the patient returned to the community hospital, where he was diagnosed with active TB. Later that month, South Carolina Department of Corrections (DOC) staff learned that another prisoner who had been released from the same HIV-segregation unit in July 1999 had been diagnosed with active TB.8
The SC DOC and the state's Department of Health and Environmental Control initiated a contact investigation, and invited collaboration from the Centers for Disease Control and Prevention. Contact investigators tracked down current prisoners who had come into contact with the source case-patient (he had participated in congregate religious activity, including bible study),9 as well as more than 100 prisoners who had lived in the source-case patient's dormitory but had since been released into the community. By the time CDC reported on the investigation in November 2000,10 over 320 current or former inmates from the HIV-segregation unit were found to have been exposed to MTB and 31 were diagnosed with TB disease. In addition, a medical student who had examined the initial source case-patient in the community hospital in July developed cavitary TB. Notably, IS6110-based DNA fingerprints of all 20 available outbreak-associated M. tuberculosis isolates were identical.11
Although the South Carolina outbreak was due to a drug-susceptible strain of TB, it was a reminder of the deadly 1990-1991 outbreak of multi-drug-resistant TB in New York prisons and jails.12 Of the 39 New York inmates identified with MDR-TB, 38 were HIV-positive.13 As an airborne infection, TB presents one of the most immediate health threats not only to prisoners, but also to correctional staff, health care providers, visitors, and others who come in close contact with TB patients.
The single most potent factor affecting the risk of progression from latent TB infection to active TB disease is HIV coinfection.14 It is often more difficult to detect active TB in persons with HIV/AIDS because they may not respond to the tuberculin skin test, and they may present atypical or negative findings on chest x-ray.15 Furthermore, significant drug interactions may complicate the concurrent treatment of HIV and TB.16 In short, HIV increases the risk of progression from TB infection to disease, makes screening for TB more difficult, and complicates the treatment of TB. (Refer to HEPPigram on page 6.)
For New York State, the 1990-1991 outbreak was a catalyst for overhauling the DOC's anti-TB efforts. TB protocols were modified to reflect heightened levels of scrutiny for HIV-infected individuals who might be harboring TB. Stepped-up monitoring and treatment resulted in a 73% decrease in the NYDOC's TB incidence rate (per 100,000 population) from 225 in 1991 to 61 in 1997.17
As recommended by the National Commission for Correctional Health Care, all prisoners should receive tuberculosis symptom screening on intake; anyone with TB symptoms (chronic productive cough, fever, weight loss, night sweats) should immediately be moved to a negative pressure respiratory isolation room and evaluated for TB disease. Tuberculin skin tests (TST) should be administered to all prisoners who have not had a previous documented positive skin test result. A TST reaction (induration at 48-72 hours) of greater than 10mm should be taken as indicative of TB infection in HIV-negative prisoners; however, in HIV-infected individuals and in recent contacts of an active case, the threshold is only 5mm. Any patient whose TST indicates TB infection, and all HIV-positive patients, should receive a chest x-ray. It should be noted that TST may fail to identify TB infection in high-risk patients including prisoners.18 TB control officers may consider using on-site chest radiography to screen all prisoners at entry (see HEPP News March 2000). HIV-positive patients with TB may be unresponsive to TST19 - and even chest x-rays may fail to demonstrate abnormalities in HIV-positive patients with TB disease. It is therefore recommended that any HIV-positive patient with respiratory symptoms undergo a sputum analysis in addition to a chest x-ray.
Prisoners with documented latent TB infection (LTBI) should complete a course of treatment.20 Several regimens are currently recommended; for HIV-positive patients not taking HAART, guidelines for treating latent TB infection are substantially similar to those for persons who are HIV-negative (see Table 1).
Those with a positive TST who cannot complete treatment for latent TB infection (LTBI) should receive regular screening for TB symptoms (South Carolina's TB Control Division recommends quarterly screening); any such patient with significant immune suppression should be scrutinized for TB symptoms even more frequently. Prisoners who clear the initial TB intake screening should be evaluated at least yearly for TST conversion, and more frequently if there is evidence of recent transmission of TB in the facility or if prisoners with HIV are housed together.21
HIV-positive persons with active TB are always candidates for HAART (if not already on HAART) since active TB infection is itself an AIDS-defining illness. While it may sometimes be feasible to delay HAART treatment in order to start treatment for TB disease, the converse is not true: there is no clinical justification for delaying the treatment of active TB.
The complicated nature of coadministering treatment for active TB and HAART is due to the fact that the rifamycin drugs used to treat TB (usually rifampin or rifabutin) stimulate the same liver enzyme systems (CYP450) that process protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs).22 Non-rifamycin TB drugs (such as isoniazid) do not generally interact with HAART medications. However, treatment of active TB in HIV-positive persons using regimens lacking a rifamycin is regarded as sub-optimal and is not recommended.23 CDC guidelines for the concurrent treatment of HIV and TB were updated in March 2000.24 Previous guidelines had advised that rifampin not be administered to an HIV-positive patient taking any PI or NNRTI, but the update advises that rifampin can probably be co-administered with these three HAART regimens:
(Data were also presented at the 8th Retroviruses Conference in Chicago in February suggesting that it may be necessary to increase efavirenz dosage to 800 mg/qd when used in combination with rifampin. See HIV 101, page 7 for a complete chart of dosages).25
In addition, the CDC had previously recommended that rifabutin could safely be used with any PI other than ritonavir and any NNRTI other than delavirdine. The new recommendations advise that rifabutin may be co-administered with ritonavir (with or without saquinavir), but that the dosage of rifabutin should be reduced substantially to 150 mg two or three times per week. While there are not substantial clinical data on the subject, the CDC recommends that it is possible to administer rifabutin with the PIs saquinavir, nelfinavir, or amprenavir and the NNRTI nevirapine without reducing the dosage of rifabutin. Rifabutin should not be used with the NNRTI delavirdine. When rifabutin is used concurrently with the NNRTI efavirenz, the dosage of rifabutin should be increased (to either 450 mg or 600 mg daily or 600 mg two or three times per week).
The exact appropriate dosages of the rifamycins (either rifampin or rifabutin) may vary depending on the exact HAART medications and dosages (See HIV 101, page 7). In HAART regimens that contain multiple PIs or PI/NNRTI combinations, there is little clinical experience and no firm guidance from CDC; state health authorities and experts in HIV/TB coinfection should be consulted. Updated guidelines and information on TB diagnosis and treatment can always be found on the CDC's Division of TB Elimination website: http://www.cdc.gov/nchstp/tb.
It should also be noted that two non-HAART drugs commonly administered to HIV-positive patients, fluconazole and clarithromycin, both cause an increase in rifabutin levels. Both fluconazole and clarithromycin cause this effect independently, and the effect is more-than-doubled when both are present. Clinicians should monitor for rifabutin toxicity (arthralgia, neutropenia, uveitis) when co-administering fluconazole and/or clarithromycin.26
Any patient taking isoniazid or pyrazinamide should be cautioned about hepatotoxicity and monitored for its symptoms, which can include nausea, vomiting, jaundice, abdominal pain, and anorexia. The risk of hepatotoxicity is probably greater in persons with acute hepatitis, chronic liver disease, injecting drug use history, prior intolerance of either medication, chronic alcoholism, or current use of interacting medications. Correctional clinicians should obtain baseline hepatic measurements of serum AST (SGOT) or ALT (SGPT) and bilirubin before starting therapy for TB infection, and may need to consider more frequent monitoring of clinical and/or biochemical status when either medication is used in treating latent TB infection. A forthcoming report (MMWR, April 2001) from the CDC will give additional data on serious adverse reactions associated with treatment for latent TB infection. Adverse reactions to a two month regimen of rifampin and pyrazinamide can be serious or even fatal, and patients should be monitored closely for liver toxicity. For additional information on optimal monitoring approaches, providers may wish to access information provided at the National TB Center TB Infoline 1-800-4TB DOCS or http://www.umdnj.edu/ntbc.
Two maxims are critical to TB control in correctional settings: "Think TB!" and "Consult an expert". TB specialists are available through the departments of public health in every state, and CDC experts are available for additional consultation. All it takes to transmit TB is to share airspace with an active TB case. Correctional providers and staff are also at risk when active TB is present in a prison or jail setting.
* HEPP News Staff Writer
** Supervisory Medical Epidemiologist, Research and Evaluation Branch, Project Officer, TB Trials Consortium, Division of TB Elimination, NCHSTP, CDC
*** Director, TB Control Division, SC Department of Health and Environmental Control
^ Nothing to disclose
1. "Prevention and Control of Tuberculosis in Correctional Facilities Recommendations of the Advisory Council for the Elimination of Tuberculosis", MMWR June 07, 1996 / 45(RR-8);1-27.
2. Hammett, TM; Rhodes, W; Harmon P 'HIV/AIDS and Other Infectious Diseases Among Correctional Inmates: A Public Health Problem and Opportunity' National HIV Prevention Conference 1999. Atlanta, GA. Abstract 571.
3. "Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates --- South Carolina, 1999--2000", MMWR November 24, 2000 / 49(46);1041-1044. Spradling P, McLaughlin S, Drociuk D, et al., "Transmission of mycobacterium tuberculosis among inmates in an HIV-dedicated prison dormitory", Abstract ThPeB5188, XIII International AIDS Conference 2000. Durban, South Africa.
4. Institute of Medicine. Ending Neglect: The Elimination of Tuberculosis in the United States. Washington, DC: National Academy Press. 2000.
5. "Notice to Readers: Updated Guidelines for the Use of Rifabutin or Rifampin for the Treatment and Prevention of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors", MMWR March 10, 2000 / 49(09);185-9.
6. CDC. Targeted tuberculin testing and treatment of latent tuberculosis infection. MMWR June 09, 2000 / 49(RR06);1-54.
7. American Health Consultants 'TB plus HIV cause big trouble for prison, jail in two Southern states' TB Monitor 2000; 7(8):77-79.
8. "Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates --- South Carolina, 1999--2000", MMWR November 24, 2000 / 49(46);1041-1044.
9. American Health Consultants 'TB plus HIV cause big trouble for prison, jail in two Southern states' TB Monitor 2000; 7(8):77-79.
10. "Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates --- South Carolina, 1999--2000", MMWR November 24, 2000 / 49(46);1041-1044.
11. "Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates --- South Carolina, 1999--2000", MMWR November 24, 2000 / 49(46);1041-1044.
12. "Transmission of Multidrug-Resistant Tuberculosis Among Immunocompromised Persons in a Correctional System -- New York, 1991", MMWR July 17, 1992 / 41(28);507-509.
13. Valway SE, Greifinger RB, Papania M, et al., "Multidrug-resistant tuberculosis in the New York State prison system, 1990-1991", J Infect Dis 1994 Jul;170(1):151-6.
14. "Targeted Tuberculin Testing and Treatment of Latent ", MMWR June 09, 2000 / 49(RR06);1-54.
15. "Drug-Susceptible Tuberculosis Outbreak in a State Correctional Facility Housing HIV-Infected Inmates --- South Carolina, 1999--2000", MMWR November 24, 2000 / 49(46);1041-1044.
16. Burman WJ, Gallicano K, Peloquin C, et al., "Therapeutic implications of drug interactions in the treatment of human immunodeficiency virus-related tuberculosis", Clin Infect Dis 1999 Mar;28(3):419-29; quiz 430.
17. Klopf LC, "Tuberculosis control in the New York State Department of Correctional Services: a case management approach", Am J Infect Control 1998 Oct;26(5):534-7.
18. Zoloth SR, Safyer S, Rosen J, et al., "Anergy compromises screening for tuberculosis in high-risk populations", Am J Public Health 1993 May;83(5):749-51.
19. Perlman DC, el-Sadr WM, Nelson ET, et al., "Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). The AIDS Clinical Trials Group (ACTG)", Clin Infect Dis 1997 Aug;25(2):242-6.
20. CDC. Prevention and control of tuberculosis in correctional facilities: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR June 07, 1996 / 45(RR-8);1-27. CDC. Prevention and Treatment of Tuberculosis Among Patients Infected with Human Immunodeficiency Virus: Principles of Therapy and Revised Recommendations. MMWR October 30, 1998 / 47(RR20);1-51.
21. CDC. Prevention and control of tuberculosis in correctional facilities: recommendations of the Advisory Council for the Elimination of Tuberculosis. MMWR June 07, 1996 / 45(RR-8);1-27.
22. Munsiff SS, Fujiwara PI 'Treatment of Tuberculosis in Patients Taking Antiretrovirals' AIDS Reader 2000; 10(2):102-108.
23. "Notice to Readers: Updated Guidelines for the Use of Rifabutin or Rifampin for the Treatment and Prevention of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors", MMWR March 10, 2000 / 49(09);185-9.
24. "Notice to Readers: Updated Guidelines for the Use of Rifabutin or Rifampin for the Treatment and Prevention of Tuberculosis Among HIV-Infected Patients Taking Protease Inhibitors or Nonnucleoside Reverse Transcriptase Inhibitors", MMWR March 10, 2000 / 49(09);185-9.
25. Lopez-Cortes LF, Ruiz R, Viciana P, et al 'Pharmacokinetic Interactions between Rifampin and Efavirenz in Patients with Tuberculosis and HIV Infection' 8th Conference on Retroviruses and Opportunistic Infections 2001. Chicago, IL. Abstract 32.
26. Jordan MK, Polis MA, Kelly G, et al., "Effects of fluconazole and clarithromycin on rifabutin and 25-O-desacetylrifabutin pharmacokinetics", Antimicrob Agents Chemother 2000 Aug;44(8):2170-2.
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©1997,1998,1999,2000,2001. The recently formed HIV Education Prison Project (HEPP) is a medical education program that targets a growing population, inmates in correctional facilities, that has been underserved in HIV care. It is part of the Brown University AIDS Program. Permission to use and reproduce portions of this newsletter is hereby granted provided that author and publication are fully credited and both copyright and permission notice appear with reprinted material. Inquiries may be directed to heppnews@brown.edu. Website: HIV Education Prison Project.
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