HHS Guidelines Panels Issue Statement on Treating Latent Tuberculosis Infection in People Infected With HIV Receiving Antiretroviral Therapy
Short-Course (3-Month) Therapy With Weekly Isoniazid-Rifapentine Is NOT RECOMMENDED for HIV-Infected Patients Receiving Antiretroviral Therapy
December 20, 2011
The purpose of this supplemental information is to alert clinicians about the use of short-course therapy with weekly isoniazid plus rifapentine (INH-RPT) for the treatment of latent tuberculosis infection (LTBI) in HIV-infected patients. Pharmacokinetic data are lacking on the interactions between RPT and antiretroviral (ARV) drugs; therefore, until such data are available, the Panel recommends the following:
Treatment of LTBI can prevent progression to active TB. INH given once daily for 9 months is the standard treatment regimen for LTBI. In an open-label, randomized non-inferiority trial, a 3-month combination regimen of INH-RPT, given by DOT once weekly, was compared with the standard 9-month self-administered once daily INH regimen for LTBI treatment.4 The study results included more than 7,000 enrolled subjects. After 33 months of follow-up, in a modified intention-to-treat analysis, 15 cases of TB were diagnosed in the INH recipients and 7 cases in the INH-RPT recipients (hazard ratio: 0.38 for INH-RPT, confidence interval [CI] 0.15-0.99, P = 0.05). The permanent discontinuation rate before treatment completion was higher in the INH alone arm. In this study, only 105 HIV-infected patients who were not receiving ART received the 3-month INH-RPT.
The 3-month regimen of INH-RPT has the advantages of shorter treatment duration, higher completion rate, and efficacy non-inferior to INH alone for 9 months. The results of this study have led to a new CDC recommendation1 in which 3-month once-weekly INH-RPT given by DOT is considered an equal alternative to the standard 9-month regimen for adults and adolescents (>12 years old). This regimen, however, is NOT recommended for HIV-infected patients receiving ART (AIII).
Rationale for NOT Recommending Short Course INH-RPT for Treatment of LTBI in HIV-Infected Patients Receiving ART
RPT is a rifamycin-antibiotic with a long plasma half-life, allowing it to be dosed less frequently than other commonly used rifamycins, such as rifampin and rifabutin. Like other rifamycins, RPT induces the cytochrome P450 enzyme system, which is responsible for the metabolism of many drugs including HIV protease inhibitors, non-nucleoside reverse transcriptase inhibitors, and maraviroc. Rifampin also induces the enzyme UGT-1A1, leading to interaction with raltegravir. No systematic study has been performed to assess the magnitude of the enzyme induction effect of RPT on the metabolism of ARV drugs and other concomitant drugs. Significant enzyme induction can result in reduced ARV drug exposure, which may compromise virologic efficacy.
Pharmacokinetic studies and clinical trials to evaluate the impact of RPT on ART are under way or in the planning stages.
The HHS Panel on Antiretroviral Guidelines for Adults and Adolescents and the HHS Panel on Antiretroviral Therapy and Medical Management of HIV-Infected Children, in consultation with:
For more detailed information regarding treatment and care for the HIV-infected patient, consult the AIDSinfo Web site: http://aidsinfo.nih.gov/Guidelines/Default.aspx.
This article was provided by AIDSinfo. Visit the AIDSinfo website to find out more about their activities and publications.
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