Rifabutin dose must be increased in patients taking efavirenz

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A study of patients with HIV and tuberculosis has confirmed that the recommended dose adjustment of rifabutin (Mycobutin) in patients also taking efavirenz (Sustiva) produces adequate levels of rifabutin in the blood. The study’s findings were presented in the 1st November edition of Clinical Infectious Diseases.

Rifabutin is often used to treat tuberculosis in patients taking antiretroviral therapy as it has fewer interactions with anti-HIV drugs than other drugs in the rifamycin class. However, studies in HIV-negative patients have shown that efavirenz can lower blood levels of rifabutin through its effects on the cytochrome P450 enzymes in the liver. This has led to treatment guidelines recommending a dose increase from 300 to 450 or 600mg when it is used alongside efavirenz-based HIV therapy.

To establish whether this recommendation is effective in a real-life setting, investigators measured the levels of rifabutin in 15 patients with HIV and tuberculosis before and after starting efavirenz-based antiretroviral therapy. None of the patients had taken a non-nucleoside reverse transcriptase inhibitor in the past, or was taking any other drug that could interact with rifabutin or efavirenz during the study.


drug interaction

A risky combination of drugs, when drug A interferes with the functioning of drug B. Blood levels of the drug may be lowered or raised, potentially interfering with effectiveness or making side-effects worse. Also known as a drug-drug interaction.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 


A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 


An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

statistical significance

Statistical tests are used to judge whether the results of a study could be due to chance and would not be confirmed if the study was repeated. If result is probably not due to chance, the results are ‘statistically significant’. 

The investigators first measured blood rifabutin levels over 21 hours when the patients had been taking 300mg rifabutin and 15mg/kg isoniazid for tuberculosis twice weekly for at least two weeks. When they started antiretroviral therapy with 600mg efavirenz once daily and two nucleoside reverse transcriptase inhibitors, the dose of rifabutin was increased to 600mg twice weekly, before rifabutin levels were measured again 21 days later.

The average 24-hour exposure to rifabutin increased by 20% from 4.2 to 5.0µg.h/ml after the addition of efavirenz, but this increase was not statistically significant (p = 0.10). This indicates that the increased rifabutin dose from 300 to 600mg was sufficient to overcome the effects of efavirenz on rifabutin levels.

The number of patients with low blood levels of rifabutin also declined after addition of efavirenz-based antiretroviral therapy: eleven (73%) of the patients had rifabutin levels below 4.5µg.h/ml at the first assessment, compared with five (33%) after addition of efavirenz (p = 0.03).

Similarly, the peak concentrations of rifabutin increased by 58% after the addition of efavirenz (p = 0.008).

When they compared the blood levels of efavirenz to those in a previous study, the investigators found similar efavirenz levels with and without rifabutin, although this could not be tested statistically. Adequate levels of efavirenz were confirmed by the effective treatment of the patients’ HIV. After a median of 21 days on antiretroviral therapy, viral loads had decreased by a median of 2.6log10 and CD4 cell counts had risen from 141 to 240 cells/mm3.

Efavirenz had no effect of blood levels of isoniazid.

“The increase in rifabutin dose from 300mg to 600mg was adequate to compensate for the drug interaction with efavirenz in most patients,” the investigators conclude. “However, additional studies are needed to characterise optimal treatment regimens for patients with HIV infection and tuberculosis”.


Weiner M et al. Evaluation of the drug interaction between rifabutin and efavirenz in patients with HIV infection and tuberculosis. Clin Infect Dis 41: 1343-1349, 2005.