Abstract
Despite the availability of effective antiretroviral therapy (ART), tuberculosis (TB) remains the leading cause of morbidity and mortality among people living with human immunodeficiency virus (PLWH). The use of effective ART can reduce the risk of developing active TB by 65%. Additional of TB preventive therapy (TPT) to ART is shown to further reduce TB incidence by 30% and mortality rate by 35-50%. Therefore, TPT is one of the important strategies for ending TB. TPT amomg PLWH in Thailand is currently implemented in clinical practice guideline2023. The preferred TPT regimen are 3 HP (weekly isoniazif 900 mg+ rifapentine 900 mg for 12 weeks)) and 1 HP (daily isoniazid 300 mg + rifapentine 450-600 mg for 4 weeks). It is crucial to investigate the drug-drug interaction to find the optimal dose of dolutegravir (DTG), the most preferred ART when it is being used with rifampin for active TB and rifapentine for TPT. This study investigated the effect of rifampin on DTG 50 mg once daily (experimental dose) versus DTG 50 mg twice daily (recommended dose) among active TB/HIV co-infection. The study demonstrated that DTG based regimen is highly effective (90% had HIV RNA < 50 copies/ml at week 48) and the standard dose DTG may be appropriate to be concomitantly use with rifampin. The study also investigated the effect of rifapentine as 1 HP or 3 HP for TPT on DTG 50 mg once daily among PLWH. The study showed that DTG based regimen is highly effective (> 95% had HIV RNA < 50 copies/ml at week 48) and the standard dose DTG may be appropriate to be concomitantly use with rifapentine. Since, fixed dose combination of DTG/tenofovir disoproxil fumarate (TDF) /lamivudine or TLD is widely used in Thailand and other low-middle-income countries (LMICs), thus, the standard dose TLD without additional DTG is more convenient for national HIV program, it is cost saving (no extra DTG dose) and the adherence of patients is not compromised (once daily ART). In those with high risk of isoniazid related hepatotoxicity such as liver disease, alcoholism, older, N-acetyltransferase 2 or NAT2 may be beneficial. The dose of Isoniazid and rifapentine or rifampin can be adjusted. Uridine glucuronosyltransferase 1A1 (UGT1A1) is also important for DTG metabolizer. In this study, rifampin, body weight and poor metabolizer of UGT1A1 are significantly affects the DTG concentration. Poor metabolizer of UGT1A1 increased DTG trough concentration by 22.8%. In summary, this study highlighs that the standad dose TLD can be safety used with both rfampin based anti TB among active TB/HIV co-infection and rifapentine based TPT. This is simple as 1 tab a day, no additioanal DTG is required. It is good for ARV procument, and cost saving. Importantly, it can be used as once a day to improve adherence. This finding is benefit for Thai PLWH and the global PLWH at large.
