HIV coinfection with tuberculosis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Recommendations for treating tuberculosis in adults with HIV infection are, with a few exceptions, the same as those for adult TB patients who are not HIV infected. However, managing HIV-related TB is complex and people with HIV and TB should seek care from a health care provider or providers with expertise in the management of both HIV disease and TB. Because persons with HIV infection are often taking numerous medications, some of which interact with anti-TB medications, experts in the treatment of HIV-related TB should be consulted.

Medical Therapy

Role of Treatment

• Without treatment, as with any other opportunistic infection, HIV and TB can work together to shorten the life of the person infected.
• Someone with untreated latent TB infection and HIV infection is much more likely to develop active TB disease during his or her lifetime than someone without HIV infection.
• Among people with latent TB infection, HIV infection is the strongest known risk factor for progressing to active TB disease.
• A person who has both HIV infection and active TB disease has an AIDS-defining condition.
• Since viral load is the single greatest risk factor for all modes of HIV transmission, ART use decreases the risk that HIV will be transmitted from one person to another.

Recommended Regimen

The recommended treatment of TB disease in HIV-infected adults (when the disease is caused by organisms that are known or presumed to be susceptible to first-line drugs) is a 6-month regimen consisting of:

• For the first 2 months: An initial phase of isoniazid (INH), a rifamycin, pyrazinamide (PZA), and ethambutol (EMB).
• For the last 4 months: A continuation phase of INH and a rifamycin.
• Patients with advanced HIV (CD4 counts < 100/µl) should be treated with daily or three-times-weekly therapy in both the initial and the continuation phases.
• Twice weekly therapy may be considered in patients with less-advanced immunosuppression (CD4 counts ≥ 100/µl).
• Once-weekly INH/rifapentine in the continuation phase should not be used in any HIV-infected patient.

Duration of Treatment

• Six months: For adults with HIV, even for patients with culture-negative TB.

• Nine months (extend continuation phase to 7 months): For HIV-infected patients with delayed response to therapy (e.g., culture positive after 2 months of treatment).

Drug Interactions

A major concern in treating TB in HIV-infected persons is the interaction of rifampin (RIF) with certain antiretroviral agents (some protease inhibitors [PIs] and nonnucleoside reverse transcriptase inhibitors [NRTIs]).

Rifabutin, which has fewer problematic drug interactions, may be used as an alternative to RIF.

WHO Recommendations

In addition to initiating earlier antiretroviral therapy (ART), WHO recommends the implementation of the "three I's" for HIV/TB to reduce the burden of TB among people living with HIV:

• Intensified TB case finding,
• Isoniazid preventive therapy,
• Infection control for TB.

WHO recommends that the Three I's for HIV/TB in addition to ART be part of a TB prevention package and that emphasize that they should be core components of HIV services with AIDS programmes and service providers taking the primary responsibility for the Three I's for HIV/TB.

National Institute of Health Recommendations

• The principles for treatment of active tuberculosis (TB) disease in HIV-infected patients are the same as those for HIV-uninfected patients (AI).
• All HIV-infected patients with diagnosed active TB should be started on TB treatment immediately (AI).
• All HIV-infected patients with diagnosed active TB should be treated with antiretroviral therapy (ART) (AI).
• In patients with CD4 counts <50 cells/mm3, ART should be initiated within 2 weeks of starting TB treatment (AI).
• In patients with CD4 counts ≥50 cells/mm3 who present with clinical disease of major severity as indicated by * clinical evaluation (including low Karnofsky score, low body mass index [BMI], low hemoglobin, low albumin, organ system dysfunction, or extent of disease), ART should be initiated within 2 to 4 weeks of starting TB treatment. The strength of this recommendation varies on the basis of CD4 cell count:
  • CD4 count 50 to 200 cells/mm3 (BI)
  • CD4 count >200 cells/mm3 (BIII)
• In patients with CD4 counts ≥50 cells/mm3 who do not have severe clinical disease, ART can be delayed beyond 2 to 4 weeks of starting TB therapy but should be started within 8 to 12 weeks of TB therapy initiation. The strength of this recommendation also varies on the basis of CD4 cell count:
  • CD4 count 50 to 500 cells/mm3 (AI)
  • CD4 count >500 cells/mm3 (BIII)
  • In all HIV-infected pregnant women with active TB, ART should be started as early as feasible, both for maternal health and for prevention of mother-to-child transmission (PMTCT) of HIV (AIII).
• In HIV-infected patients with documented multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB, ART should be initiated within 2 to 4 weeks of confirmation of TB drug resistance and initiation of second-line TB therapy (BIII).
• Despite pharmacokinetic drug interactions, a rifamycin (rifampin or rifabutin) should be included in TB regimens for patients receiving ART, with dosage adjustment if necessary (AII).
• Rifabutin is the preferred rifamycin to use in HIV-infected patients with active TB disease on a protease inhibitor PI)-based regimen because the risk of substantial drug interactions with PIs is lower with rifabutin than with rifampin (AII).
• Coadministration of rifampin and PIs (with or without ritonavir [RTV] boosting) is not recommended (AII).
• Rifapentine (RPT) is NOT recommended in HIV-infected patients receiving ART for treatment of latent TB infection (LTBI) or active TB, unless in the context of a clinical trial (AIII).
• Immune reconstitution inflammatory syndrome (IRIS) may occur after initiation of ART. Both ART and TB treatment should be continued while managing IRIS (AIII).
• Treatment support, which can include directly observed therapy (DOT) of TB treatment, is strongly recommended for HIV-infected patients with active TB disease (AII).

References

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