Important note: Information in this article was accurate in March 1999. 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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The incidence of tuberculosis (TB) is three times higher inside correctional settings than outside, making mastery of TB treatment guidelines a "must" for correctional HIV professionals. Updated guidelines highlighting new regimens and clinical practices for the treatment of tuberculosis (TB) and human immunodeficiency virus (HIV) co-infected individuals were just published (CDC, 1999 1). The guidelines re- emphasize previously well-recognized principles of TB treatment, and extend these concepts to TB in the context of HIV co-infection. The following article will review these recent developments and provide insight into the complex issues surrounding the care of TB and HIV infected individuals in the correctional setting.
Initial studies of TB and HIV concentrated on the impact of HIV on the natural progression of TB. HIV infected individuals appear to be more likely to be infected with TB if exposed, compared to non-HIV infected individuals. Once infected, the natural history of TB progression from infection to disease and death may be telescoped into a matter of weeks in the HIV infected individual.
More recent studies have revealed that the impact of TB on the progression of HIV may be just as devastating. The host immune response to Mycobacterium tuberculosis (Mtb), the causative agent of TB, appears to increase HIV replication, both systemically and locally. In some patients with active TB, plasma HIV RNA levels (viral load) rise substantially before TB is diagnosed and viral loads fall with TB treatment alone (Havlir, Barnes, 1998 -- see reference 2). These facts serve therefore to underscore the absolute importance of prevention, early recognition and effective treatment of both TB and HIV in the correctional setting.
Decisions regarding treatment of active tuberculosis are constrained by the choice of HIV treatment regimen (see Table 1, page 3, for a detailed summary of treatment regimens for TB/HIV co-infected patients). Therefore, the HIV infection status of the patient should be ascertained prior to initiation of TB prophylaxis or early in the treatment of active disease.
Two new classes of drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTI’s) and protease inhibitors (PI's), are known to interact with rifampin, one of the drug cornerstones of TB treatment. Rifampin, a potent inducer of the cytochrome P450 system, reduces the levels of PI's and NNRTI's in the plasma; reduction in plasma levels of these drugs to less than therapeutic levels may lead to the development of resistant mutations of the HIV virus. Furthermore, NNRTI's and PI's may impair the clearance of rifampin, thereby predisposing the patient to drug side effects.
One of the new CDC recommendations is to use rifabutin to replace rifampin in TB treatment regimens when patients are on NNRTI's and PI's. Because of the possibility that a rifabutin-containing regimen may reduce the long-term efficacy of the TB treatment regimen, it is now recommended that a four-drug regimen, including rifabutin, be used to treat TB for the first 2 months, even if drug susceptibility is demonstrated.
If the HIV infected patient is already on PI’s or NNRTI’s, interruption of the HIV treatment regimen is not recommended; modification of the TB treatment to allow for the use of the PIs and NNRTIs is preferred. However, if the diagnoses of TB and HIV are made simultaneously, the relative risks of simultaneous initiation of therapy for both diseases versus the treatment of TB first must be considered on a case-by-case basis. Three options are available: (1) TB can be treated alone for at least 2 months with subsequent modification of the standard TB regimen (see Table 1); (2) TB can be treated for 6 months with subsequent initiation of HIV therapy; (3) Simultaneous HIV and TB treatment may be initiated with rifabutin, substituting rifampin if PI’s or NNRTI’s are used for HIV therapy. By implication, the clinician must assess whether it is appropriate to delay treatment of HIV infection in favor of treating TB disease. Delaying treatment of active TB disease, in favor of treating HIV first, is not a clinical option.
Adherence to TB therapy has been emphasized for years as the most important principle in the treatment of TB disease. Concomitant treatment of TB and HIV requires meticulous adherence to both sets of drugs. The patient must be taught that each of the drugs has an effect on the other. For example, if the patient becomes nonadherent with the HIV medications, the serum rifabutin level will fall and may place the patient at risk for the development of drug resistant TB. Nonadherence in this scenario may lead not only to resistant TB, but also to resistant HIV. It does, therefore, entail a double risk.
Treatment of drug resistant forms of TB in the setting of HIV is not discussed in-depth here because it is complex and requires individualization. Identifying MDRTB by doing appropriate cultures is an important first step. Correctional HIV providers should send appropriate clinical specimens from every suspected or active TB case to competent microbiology laboratories for culture and sensitivity testing. Should correctional providers identify a case of MDRTB, they should take the opportunity to obtain consultation with their state TB control officers and to confer with physicians experienced in the management of drug resistant TB.
Directly observed therapy (DOT) is accepted as the standard mechanism for ensuring adherence both inside and outside of the correctional setting and is recommended by the World Health Organization (WHO). The use of fixed dose combination pills is an additional option, which may eliminate the patient's ability to selectively uncouple drug regimens. Unfortunately, fixed dose combinations are not available for all drug combinations and no fixed dose combination is available that includes rifabutin. Because it is feasible in the correctional setting, DOT for all TB regimens (including prophylaxis) is already the standard of care.
Obviously it is much easier and safer to treat TB in its latent form than in its active form. Therefore, screening for TB infection is an important part of the annual health care evaluation of the HIV infected individual. A PPD (TB skin test) of greater than 5 mm in duration is considered to be an indication of TB infection in HIV infected individuals: 10 mm is the cutoff for incarcerated patients who are not HIV seropositive. Clearly, the HIV risk status of the patient should be assessed and HIV testing should be advised if appropriate, as HIV-infection status affects the interpretation of the TB skin test. Careful clinical history documentation may sometimes reveal a history suggestive of TB exposure, which would hold as much or greater weight in the decision to initiate therapy for TB infection as would a positive PPD. In fact, the most important requirement before initiating therapy for latent tuberculosis is a careful history and physical combined with appropriate radiographic screening to rule out active TB.
There are three options for the treatment of TB infection in the HIV infected individual. Note that the following regimens incorporate some new concepts in TB treatment. All of the following regimens should be provided via DOT in the correctional setting:
Individuals who complete an adequate course of therapy (whether for TB infection or TB disease) require no specific follow-up screening care unless they have symptoms of active TB or are subsequently re-exposed to an individual with infectious TB. The problem here is how to ensure adequacy of therapy whenever DOT is not utilized.
Correctional HIV providers need to take advantage of their DOT option for these regimens. It is important to develop methods of confirming DOT: you may wish to ask the medline staff to keep a separate record of DOT treatment for TB, and to notify you if more than one dose is missed in a given period. Even if medline keeps track of a patient's adherence to TB medications, you may wish to keep your own records; a standard calendar can serve as a DOT flow sheet. While DOT may be facilitated by the correctional environment, continuity of care of a TB/HIV co-infected patient may be challenged by transfers between correctional facilities and treatment in the community setting.
The issues raised in this article serve to underscore the importance of close communication between service providers should a patient's TB and HIV regimens be administered by different physicians within the correctional and community settings.
1. CDC." Prevention and treatment of Tuberculosis among individuals infected with Human Immundeficiency Virus: Principles of therapy and revised recommendations." MMWR 1998: 47 (No. RR-20)
2. Havlir, DV, Barnes, PF." Tuberculosis in patients with Human Immunodeficiency Virus infection." N Engl J Med 1999 Feb 4;340(5):367-73
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