Figure 2.
Summary of data and guidelines regarding short-course latent tuberculosis infection treatment and alternative antiretroviral (ARV) regimens. (A) Isoniazid regimens are not shown. There are no drug-interactions with ARVs that preclude usage of isoniazid, although additive liver toxicity should be assessed with some ARVs. (B) The National Tuberculosis Controller’s Association (NTCA)/Centers for Disease Control and Prevention (CDC), US Department of Health and Human Services (DHHS) HIV Adult ART, and European AIDS Clinical Society (EACS) guidelines suggest that rifabutin (RBT) can be used in place of rifampin (RIF) [15, 19, 20], but there are no efficacy data to support this, and the use of RBT should be limited to scenarios in which there are no alternatives. (C) No interaction is expected between tenofovir disoproxil fumarate (TDF) and RIF, and TDF can be considered as a replacement for tenofovir alafenamide (TAF). Rifampin decreased plasma TAF area under the curve (AUC) by 55% and intracellular tenofovir-diphosphate (TFV-DP) concentrations by 36%; however, intracellular TFV-DP concentrations during RIF/TAF coadministration were more than 4 times greater than those achieved by TDF alone [51]. The DHHS guidelines indicate “do not coadminister, unless benefits outweigh risks” [14]. The EACS guidelines suggest “administer TAF BID” [15]. The World Health Organization (WHO) TB preventive treatment guidelines indicate “contraindicated” [1]. The University of Liverpool drug interaction checker suggests “coadministration is not recommended. If coadministration required, use TAF 25 mg twice daily” [61]. (D) Data on the coadministration of weekly RPT (in 3HP), daily RPT (in 1HP), and RBT with TAF are limited, but emerging data suggest these combinations may be considered. Based on the RIF drug-drug interaction study, intracellular TFV-DP is still adequate with RIF/TAF coadministration [51]; and the interaction with TAF is greatest for RIF and daily RPT compared with other rifamycins (RIF~daily RPT > weekly RPT > RBT). The DHHS OI guidelines indicate “do not coadminister” for TAF with RBT or RPT [14]. The EACS guidelines indicate, “consider administration of TAF BID” for RBT and do not comment on RPT [15]. The WHO indicates all rifamycins with TAF are “contraindicated” [1]. The University of Liverpool drug interaction checker suggests “coadministration is not recommended. If coadministration required, use TAF 25 mg twice daily” for all rifamycins [61]. (E) In the DOLPHIN study, DTG AUC decreased by 26% and Cmin by 47% with weekly RPT coadministration, but all patients maintained an undetectable viral load with 59 of 60 of patients with troughs above the 90% MIC [56]. The WHO guidelines suggest DTG may be used with 3HP based on this study [1]. DHHS HIV Adult ART guidelines indicate, “do not coadminister” with RPT [20]. The EACS guidelines do not comment on RPT regimens [15]. The University of Liverpool interaction checker suggests that “coadministration may decrease DTG… magnitude is predicted to be lower than with rifampicin” [61]. (F) TheWHO guidelines suggest DTG may be used with 1HP [1], but there are no clinical trial data to support this. (G) Daily RPT is expected to reduce RAL Cmin 41% [40]. Whether this interaction can be overcome by increased dosing is uncertain and the optimal dosing strategy with daily RPT is unknown [61]. The WHO guidelines suggest RAL may be used with 1HP [1], but DHHS guidelines advise against daily RPT with RAL [14].