When rifabutin and Kaletra were co-administered for 10 days, rifabutin (parent drug and active 25-O-desacetyl metabolite) Cmax and AUC were increased by 3.5- and 5.7-fold, respectively. When given with Kaletra the recommended dose of rifabutin is 150 mg 3 times per week on set days (for example Monday-Wednesday-Friday). Increased monitoring for rifabutin-associated adverse reactions including neutropenia and uveitis is warranted due to an expected increase in exposure to rifabutin. Further dosage reduction of rifabutin to 150 mg twice weekly on set days is recommended for patients in whom the 150 mg dose 3 times per week is not tolerated. It should be kept in mind that the twice weekly dosage of 150 mg may not provide an optimal exposure to rifabutin thus leading to a risk of rifamycin resistance and a treatment failure. No dose adjustment is needed for Kaletra.
Kaletra Summary of Product Characteristics, AbbVie Ltd, January 2021.

Coadministration of rifabutin (150 mg once daily) and lopinavir/ritonavir (400/100 mg twice daily) to 14 HIV- subjects resulted in increases in lopinavir Cmax, AUC and Cmin of 8%, 17% and 20% respectively. Data in 12 subjects, and compared to rifabutin 300 mg once daily alone, showed increases in rifabutin Cmax, AUC and Cmin of 2.1-, 3.0- and 4.9-fold. Cmax, AUC and Cmin for 25-O-desacetyl rifabutin increased by 23.6-, 47.5- and 94.9-fold. Dosage reduction of rifabutin by at least 75% of the usual dose of 300 mg/day is recommended (i.e., a maximum dose of 150 mg every other day or three times per week). Increased monitoring for adverse events is warranted in patients receiving the combination. Further dosage reduction of rifabutin may be necessary. 
Kaletra Prescribing Information, AbbVie Ltd, October 2020.

Patients with TB-HIV co-infection (n=16) received rifabutin (300 mg once daily) in combination with tuberculosis chemotherapy (initially pyrazinamide, isoniazid and ethambutol then only isoniazid), and were then randomized to receive isoniazid and lopinavir/ritonavir based ART with rifabutin (150 mg three times weekly or 150 mg daily). The rifabutin dose with ART was switched after 1 month. Rifabutin AUC and Cmax in patients taking 150 mg rifabutin three times weekly was significantly reduced compared to the other treatment arms: AUC and Cmax decreased by 40% and 50% when compared to 300 mg once daily, and decreased by 60% and 50% when compared to 150 mg daily. 86% of patients on the three times weekly rifabutin arm had an AUC < 4.5 μg.h/mL, which has previously been associated with acquired rifamycin resistance. Plasma d-RBT concentrations increased 5-fold with three times weekly rifabutin dosing and 15-fold with daily doses of rifabutin. Rifabutin was well tolerated at all doses and there were no grade 4 laboratory toxicities. A daily 150 mg dose of rifabutin in combination with lopinavir/ritonavir safely maintained rifabutin plasma concentrations in line with those shown to prevent resistance. 
Randomized pharmacokinetic evaluation of different rifabutin doses in African HIV- infected tuberculosis patients on lopinavir/ritonavir-based antiretroviral therapy. Naiker S, Connolly C, Wiesner L, et al. BMC Pharmacol Toxicol, 2014, 15:61.

A randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis evaluated rifabutin pharmacokinetics before and after the introduction of lopinavir/ritonavir. Rifabutin and 25-O-desacetyl rifabutin concentrations were measured after 2 weeks of rifabutin 300 mg daily alone, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir (n=12) and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir (n=13). Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2-5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations.
Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam. Lan NT, Thu NT, Barrail-Tran A, et al. PLoS One, 2014, 9(1): e84866.