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Tapping into the possibility of treating tuberculosis with rifampicin in patients taking boosted protease inhibitor (bPI)
1 March, 2012
One of the leading causes of death among people living with HIV, tuberculosis remains a serious threat for HIV-infected people. Antiretroviral drugs from a class called "Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI)" are recommended for patients who take rifampicin (RIF), a cheaper, widely used anti-TB drug. However, some patients cannot tolerate side effects of NNRTI medications since they can cause serious dizziness and rashes. Globally, if patients with TB and HIV co-infection have failed or cannot tolerate NNRTI treatment, they will have limited treatment options and will likely be recommended to take boosted protease inhibitor (bPI) with rifabutin, a more expensive anti-TB treatment, instead of rifampicin.
Rifampicin is used to treat TB In resource-limited countries. Unfortunately, it is not recommended to use rifampicin in HIV-infected people who take bPI because the HIV drug will not be as effective. Moreover, according to a study, the drug interaction can increase levels of liver enzymes in healthy uninfected people, negatively affecting liver function. Physicians then opt for rifabutin, which is more expensive and usually not available in countries with high rates of HIV-related tuberculosis.
But is it possible to use rifampicin to treat TB in patients taking bPI?
Realizing the importance of creating new alternatives for people with TB/HIV co-infection, the study team led by Dr. Anchalee Avihingsanon conducted a research on HIV-infected volunteers who take bPI and rifampicin to investigate the safety and efficacy of using both drugs. Indinavir (IDV), one of the bPI medications, was selected because it was widely used in Thailand at that time. The standard dose for Thai patients is 400 mg of IDV and 100 mg of ritonavir (RTV) administered twice per day. In this study, 1.5 times the standard dose of Indinavir and the standard dose of ritonavir administered twice per day were used during TB treatment with rifampicin. When the TB treatment was stopped, IDV and RTV were reduced to standard dose administered twice per day.
This study found that HIV-infected patients with active TB could use 600 mg of IDV and 100 mg of RTV administered twice per day with rifampicin, as it was found that levels of liver damages were lower than what was reported in studies conducted in healthy volunteers. However, this resulted in patients having lower drug concentrations of IDV in the blood which can lead to treatment failure. As a result, frequent monitoring of drug concentrations is recommended.
Further research is needed to establish safety and efficacy of this regimen. The regimen is not recommended for patients unless specified otherwise in the treatment guideline.
"Pharmacokinetics and 48 week efficacy of adjusted dose indinavir/ritonavir in rifampicin treated HIV/tuberculosis co-infected patients: a pilot study" is published in the journal entitled, "AIDS Research and Human Retroviruses" on 17 January 2012.
Original abstract is available in pubmed: Click here
Avihingsanon A, van der Lugt J, Singphore U, Gorowara M, Boyd M, Ananworanich J, Phanuphak P, Burger DM, Ruxrungtham K. Pharmacokinetics and 48 week efficacy of adjusted dose indinavir/ritonavir in rifampicin treated HIV/tuberculosis co-infected patients: a pilot study. AIDS Hum Retroviruses 2012 Jan 17
For inquiries about this manuscript, you can contact the corresponding author Anchalee Avihingsanon at anchalee.a@hivnat.org.
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