Xiaoqin Le1, Xiaoye Guo2, Jianjun Sun1, Li Liu1, Yinzhong Shen1, Jiangrong Wang1, Tangkai Qi1, Zhenyan Wang1, Yang Tang1, Wei Song1, Lin Yin3, Lijun Zhang3, Renfang Zhang4, Jun Chen5. 1. Department of Infection and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 2. The Fifth People's Hospital of Wuxi City, Jiangsu Province. 3. Scientific Research Center, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 4. Department of Infection and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: zhangrenfang@shphc.org.cn. 5. Department of Infection and Immunology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. Electronic address: qtchenjun@163.com.
Abstract
BACKGROUND: Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection. METHODS: Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed. RESULTS: A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57). CONCLUSIONS: Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.
BACKGROUND: Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection. METHODS: Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed. RESULTS: A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57). CONCLUSIONS: Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.
Authors: Maria A Mendoza; Mohammad H Alshaer; Giovanni Roldan; Jose Guillermo Castro; David Ashkin; Charles A Peloquin; Catherine V Boulanger Journal: J Int Assoc Provid AIDS Care Date: 2022 Jan-Dec