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The article by Decloedt et al. describes the pharmacokinetics (PK) of ritonavir (RTV)-boosted lopinavir (LPV/r) at different doses when combined with rifampin in patients with HIV infection but without TB coinfection [1].
The coexistence of HIV and TB infections is quite common, especially in resource-limited settings where millions of patients are affected [101]. Coinfection leads to increased morbidity and mortality and several problems in management, such as additive toxicity, drug interactions, availability and cost of the treatment. Current HIV guidelines recommend initiating antiretroviral (ARV) therapy soon after anti-TB drugs, within the first 8 weeks if possible, especially with low CD4 counts [102-104]. This leads to a decrease in morbidity and mortality from both diseases, although with higher risk of immune reconstitution inflammatory syndrome [2].
Rifampin is a major inducer of cytochrome P450 enzymes and p-glycoprotein efflux pump [3]. Some ARV drugs, mainly protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), are metabolized using these enzymatic systems. These interactions are especially important with PIs and when administered with rifampin, their minimum concentrations (C min ) decrease significantly despite RTV boosting, contraindicating its coadministration [4-7]. Another problem of rifampin-PI combination is a higher incidence of hepatotoxicity and other side effects, mainly gastrointestinal [8-10]. Decreases in efavirenz (EFV) C min are less marked [11,12], and for this reason it is the third drug of choice when rifampin is used [102].
However, some patients are not able to receive EFV due to adverse effects, pregnancy or resistance and other options have to be considered, including adjusted-dose PI/r-based regimens, as in the current study [103].
Methods
This was an open-label, sequential, four-period study with different twice-daily (b.i.d.) LPV/r doses in adult black South African HIV-infected patients, without TB, who were previously receiving LPV/r tablets plus two nucleoside reverse transcriptase inhibitors (NRTIs) and had a HIV viral load <400 copies/ml. Patients with hepatic disease (defined as ALT above 1.5-times the upper normal limit, positive hepatitis B surface antigen or hepatitis C antibody), excessive alcohol consumption, TB suspicion, pregnancy, lipid alterations, diabetes or those taking other drugs that could interact with LPV/r were excluded.
Steady-state intensive 12-h PK of LPV and RTV were performed using noncompartmental methods. Liquid chromatography-mass spectrometry was used. On PK at day 1, patients were receiving...