FAQ
Tuberculosis in human immunodeficiency virus (HIV) patients: managing drug interactions
Patients with human immunodeficiency virus (HIV) frequently develop opportunistic infections due to their immune status; one of the most common of which is tuberculosis. The treatment of tuberculosis in patients with HIV is complicated due to the potential drug-drug interactions that may occur with their antiretroviral and antimycobacterial therapies. The main concern is interactions with rifamycins (rifabutin, rifampin, and rifapentine), which induce the cytochrome (CYP) P450 isoenzyme system. Rifamycins are essential for appropriate treatment of tuberculosis, and regimens without a rifamycin have proven to be less effective, especially in patients with HIV. Rifampin is the most common agent used based on widespread availability, whereas rifabutin is difficult to obtain in some countries. In addition, the concentration of rifabutin may be reduced by certain antiretroviral agents.
The Centers for Disease Control and Prevention (CDC) has provided clinicians with updated information (December 2007) for managing these interactions. One of the main reasons for the updated document is to incorporate clinical experience to supplement pharmacokinetic data. The interactions and CDC recommendations are summarized in the table below.
Table. Summary of rifamycin interactions with antiretroviral therapy.
| Rifamycin | Object drug | Interaction(s) | Recommendation/comments</b> |
| rifampin (strongest CYP inducer) | efavirenz | Reduction in efavirenz concentration by 20% | Use standard doses of each agent, as the effect has been shown to be clinically insignificant. May increase the efavirenz dose to 800 mg twice daily for patients who weigh >60 kg. |
| nevirapine | Reduction in nevirapine concentration by 20% to 55% Overlapping toxicities exist with antituberculosis drugs. | Concerns exist for concurrent use due to overlapping toxicity with antituberculosis drugs. Standard dose nevirapine appears to be the preferred option if combination therapy is desired. | |
| protease inhibitors (PIs) | Reduction in PI concentrations by >90% | Cannot use concurrently, change to rifabutin. Some literature has evaluated the use of increasing the dose of ritonavir-boosted PI from 100 mg to 200 mg to 400 mg, but hepatotoxicity has occurred. | |
| maraviroc | Reduction in maraviroc concentration | No clinical experience; maraviroc dose should be increased to 600 mg twice daily according the prescribing information. | |
| raltegravir | Reduction in raltegravir concentrations by 60% | Limited clinical experience exists, may use standard dose raltegravir (400 mg twice daily) | |
| rifabutin (weakest CYP inducer) | PI | No affect on PI concentrations; rifabutin concentrations are increased dramatically. | Rifabutin is the rifamycin of choice for patients with HIV who must take antiretroviral therapy with PIs during tuberculosis treatment. Rifabutin should be given at a reduced dose such as 150 mg per day or 300 mg thrice weekly. |
The CDC guidelines also address concurrent therapy in pregnant women and children and multidrug-resistant tuberculosis; however, data are limited in these populations. Nevirapine-based regimens are recommended for pregnant women who need rifampin therapy; however, liver function should be monitored. Efavirenz is a potential option, but not in the first 2 trimesters. Rifabutin therapy in women treated with PIs is the preferred option.
For children, lopinavir-ritonavir with additional doses of ritonavir is recommended for children receiving rifampin. An alternative, is an antiretroviral regimen containing 3 nucleoside reverse transcriptase inhibitors (NRTIs). Efavirenz-containing regimens are appropriate for older children being treated with rifampin.
No specific recommendations are provided for multidrug-resistant tuberculosis due to a lack of information about the metabolism and pharmacokinetic properties of a majority of the second-line agents.
Practitioners who treat patients with HIV should be aware of the potential interactions between antiretroviral therapy and rifamycins and consult the CDC guidelines for recommendations.
References
Centers for Disease Control and Prevention. Managing drug interactions in the treatment of HIV-related tuberculosis, December 2007. Available at: http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm. Accessed February 29, 2008.
Selzentry [package insert]. New York, NY: Pfizer; 2007.