604. Effect of rifabutin in dolutegravir dosing: a case series

Abstract Background Tuberculosis (TB) is the leading cause of death in human immunodeficiency virus (HIV) infected people worldwide. Patients with HIV who have latent TB are 20-30 times more likely to develop active TB. Integrated antiretroviral therapy (ART) early treatment for tuberculosis recommended due improved morbidity and mortality, however, there can be serious drug interactions. Rifamycins potent inducers CYP3A4 isoform, which sub-therapeutic concentrations anti-retroviral drugs, among these, rifabutin (RBN) a less inducer CYP3A4. Pharmacokinetic (PK) studies done on healthy adults showed that rifampin decreased dolutegravir (DTG) by than 50 % whereas RBN it 30%. has been preferred given its favorable pharmacokinetic toxicity profile. Currently no examining use DTG co-infected persons. This case series 4 patients receiving both agents underwent PK analysis. Methods Retrospective analysis respiratory care unit (RCU) at Jackson Memorial Hospital Miami. We included adult patients, admitted RCU, concomitant diagnosis disease received RBN, plasma were measured therapeutic monitoring (TDM). A non-compartmental was performed area under concentration-time curve (AUC) calculated RBN. Results report (Figure 1) met criteria All treated had low DTG, requiring higher doses (Table 1 & 2). After adjustments based analysis, evidence response 2 robust others. Adequate suppression viral load could not determined 3 because short observation time. Figure 1:Timelines describing admission providedDTG, dolutegravir. RFB, rifabutin. VL, load. AFB, Acid fast bacilli. LAD, lymphadenopathy. TAF, Tenofovir alafenamide. FTC, Emtricitabine. TDF, Disoproxil Fumarate. INH, Isoniazid. PYZ, Pyrazinamide. BID, twice day. QD, daily. IRIS, Immune reconstitution inflammatory syndrome. GU, genitourinary. TB, tuberculosis.Table 1:Patients’ pharmacokinetics DTGAUCX-Y, from time X Y hours; AUC0-tau, zero end dosing interval; dolutegravir; TDM, monitoring. a) AUC0-6 calculated.Table 2:Patients’ RBNAUCX-Y, Rifabutin; every 24 hours, b) value trace AUC calculated. Conclusion DTG. demonstrates optimal highly TDM. Prospective clinical needed further determine interactions between virologic treatment. Disclosures Authors: No reported disclosures.