Doubling LPV dose or adding RTV overcomes impact of rifampicin
South African people taking a lopinavir/ritonavir-based antiretroviral combination and a rifampin (rifampicin)-based anti-TB regimen generally responded well to a doubling of the lopinavir dose or to an additional 300 mg of ritonavir to overcome the impact of rifampin on lopinavir concentrations.
Previous research showed that rifampin dramatically reduces lopinavir concentrations when the two drugs are taken together. Doubling the lopinavir dose or adding ritonavir offset this interaction but often caused liver toxicity in healthy volunteers.
Researchers in South Africa assessed these strategies in HIV/TB-positive adults already taking lopinavir/ritonavir and rifampin. Study participants either doubled the lopinavir dose or added 300 mg of ritonavir daily. The investigators measured steady-state lopinavir levels before dosing (minimum concentrations) every second month.
The study involved 18 people observed for 79 patient-months. Eleven of the 18 continued follow-up until they completed their TB regimen.
During TB therapy the median lopinavir minimum concentration was 6.8 mg/L (interquartile range 1.1 to 9.2). Thirty-six of 47 lopinavir concentrations (77%) were above the recommended trough of 1 mg/L.
Study participants tolerated the lopinavir and rifampin regimens well, with no grade 3 or 4 toxicity. Grade 1 or 2 transaminase elevations developed in 8 people (44%). One patient stopped taking additional ritonavir because of nausea, and 1 patient needed a dose reduction because of diarrhea.
In 11 patients with viral loads available after TB therapy, 10 had an undetectable load.
The researchers conclude that these strategies yield adequate lopinavir concentrations in people taking rifampin, noting that “the isolated subtherapeutic measures were most likely due to poor adherence.”
They note that adding ritonavir is complicated by the increased pill burden and low-temperature storage instructions for ritonavir. In an earlier study of healthy volunteers, adding ritonavir tended to cause more toxicity than doubling the lopinavir dose. Therefore they suggest an adequately powered trial to assess the safety and efficacy of doubling the lopinavir dose in patients with tuberculosis.
Until results of larger studies are available, the authors recommend monitoring transaminases regularly during cotreatment with lopinavir and rifampin.
Source: Eric H. Decloedt, Gary Maartens, Peter Smith, Concepta Merry, Funeka Bango, Helen McIlleron. The safety, effectiveness and concentrations of adjusted lopinavir/ritonavir in HIV-infected adults on rifampicin-based antitubercular therapy. PLoS One. 2012; 7(3): e32173.
Complete article provided by PLoS One, an open-access journal
