2021
DOI: 10.1016/j.crphar.2021.100044
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Pharmacokinetic drug interactions of integrase strand transfer inhibitors

Abstract: The integrase strand transfer inhibitor (INSTI)-containing regimens are currently considered as the first-line treatment of human immunodeficiency virus (HIV) infection. Although possessing a common mechanism of action to inhibit HIV integrase irreversibly to stop HIV replication cycle, the INSTIs, including raltegravir, elvitegravir, dolutegravir, and bictegravir, differ in pharmacokinetic characteristics. While raltegravir undergoes biotransformation by the UDP-glucuronosyltransferases (UGTs), elvitegravir i… Show more

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Cited by 21 publications
(11 citation statements)
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References 61 publications
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“…While co-formulated single-tablet InSTI-containing regimens have become the recommended first-line HIV treatment regimens 12 , concerns about adverse effects and drug-drug interactions cause the hesitancy to initiate TBI treatment in this cohort. Indeed, co-administration of rifapentine significantly decreases the plasma concentrations of InSTIs due to rifapentine-mediated CYP3A and UGT1A1 induction 33 . In a phase 1/2 trial conducted among 61 PLWH concurrently receiving DTG-containing regimens and 3HP, a 36% increase in DTG clearance was observed; however, only one had trough concentration below the 90% maximal inhibitory concentration for DTG and all participants were able to maintain HIV viral suppression during 3HP treatment 13 .…”
Section: Discussionmentioning
confidence: 99%
“…While co-formulated single-tablet InSTI-containing regimens have become the recommended first-line HIV treatment regimens 12 , concerns about adverse effects and drug-drug interactions cause the hesitancy to initiate TBI treatment in this cohort. Indeed, co-administration of rifapentine significantly decreases the plasma concentrations of InSTIs due to rifapentine-mediated CYP3A and UGT1A1 induction 33 . In a phase 1/2 trial conducted among 61 PLWH concurrently receiving DTG-containing regimens and 3HP, a 36% increase in DTG clearance was observed; however, only one had trough concentration below the 90% maximal inhibitory concentration for DTG and all participants were able to maintain HIV viral suppression during 3HP treatment 13 .…”
Section: Discussionmentioning
confidence: 99%
“…Each drug with 3 doses was added into a culture medium and incubated, Mito-Tox was evaluated in 3D spheroids, as compared to 2D cultures a three-time points (3 day, 2, and 4 weeks) Three FDA approved anti-HIV drugs were tested compared to two controls, including (1) ddC (0.1, 2, 10 µM) [ 39 , 40 ] known for significantly inducing Mito-Tox, 0.1 µM ddC is a typical single dose maximal plasma concentration (Cmax) [ 40 ]; (2) TFV (3, 30, 300 µM) [ 41 , 42 , 43 ] known for inducing only minimal Mito-Tox, 2.12µM TFV is a typical single dose maximal plasma concentration [ 40 , 41 , 42 , 43 , 44 ] (3) RAL (2, 20, 200 µM) [ 45 , 46 , 47 ] that is controversial in its ability to cause Mito-Tox, 2.25 µM is a typical RAL maximal plasma concentration [ 48 ], (4) rotenone (10 µM) [ 49 ] as a positive control; and (5) 0.1% DMSO as a negative control, see Table 1 .…”
Section: Methodsmentioning
confidence: 99%
“…Moreover, the consensus was reached that HRQoL reported by PLWH is better in single tablet regimens (STR) than in multi-tablet regimens and that HRQoL monitoring over time assesses the experience of drug burden (number of tablets, food restrictions, ease of intake) and symptoms associated with treatment regimes. The complexity of the pharmacological burden, identifiable in the definition of polypharmacy, entails consequences for care, but also ethical, social and economic, while the concepts of deprescribing and therapeutic optimization might allow the reduction of potentially inappropriate drugs and drug-drug interactions, with the ultimate aim of improving the patient's quality of life [48][49][50][51]. The final statements are reported in Figure 4.…”
Section: Quality Of Lifementioning
confidence: 99%