Although rifapentine/isoniazid decreased DTG bioavailability, all viral loads were suppressed. DTG may be co- administered with 3HP without dose adjustment.
DTG Vs. rifapentine/isoniazid
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Study Design
HIV infected adults with undetectable viral load on efavirenz (EFV)- based regimens were recruited into 3 groups. All received DTG in place of EFV for 8 weeks, then began 12 once weekly rifapentine/isoniazid dose; after rifapentine/isoniazid completion, all participants were followed 4 more weeks. Viral loads were measured at baseline and weeks 11 and 24. Groups 1A (n=12) and 1B (n=18) had intensive DTG PK sampling performed at week 8 (pre-HP), then weeks 11 and 16 following the 3rd and 8th doses of HP. Group 2 (n=30) were treated with the same schedule and had sparse DTG PK sampling
at weeks 8, 11 and 16. Primary endpoints were 1) grade >3 AE and 2) population PK parameters of DTG with or without rifapentine/isoniazid.
Study Results
Of the 60 participants who received 3HP, 43 (70%) were female, median (IQR) age was 40 (35-48) years, all were black African, median (IQR) CD4 was 683 (447-935) cells/mm3, and median (IQR) BMI was 28.9 (24.0-32.9) kg/m2. All participants received ≥6 rifapentine/isoniazid doses at the time of this report. ThreeGrade 3 AE occurred (2 elevated creatinine, 1 hypertension). HIV viral loads at baseline, day 58 (pre-rifapentine/isoniazid), day 72 (3rd rifapentin/isoniazid dose) and day 168 (post-rifapentine/isoniazid) were all <40 c/mL. The geometric mean (GM) trough concentration of DTG on Day 58 (pre-rifapentine/isoniazid) was 1003 ug/mL (5th-95th %ile: 500-2080), and during rifapentine/isoniazid treatment 546 (134-1616) with all trough levels but one above DTG IC90 of 64 ug/mL; ). Overall, rifapentine/isonizid administration decreased DTG bioavailability by 29% (RSE 13%) (+18%, -37% and -35% for week 1, 3 and 8), while clearance remained unchanged.
Study Conclusions
The authors concluded that co-administration of DTG and rIfapentine/isoniazid was well-tolerated, with no rifapentine/isoniazid-related Grade >3 AEs. Although rifapentine/isoniazid decreased DTG bioavailability, which was associated with a modest decrease in trough levels, all trough levels but one were above the DTG IC90. All viral loads were suppressed. DTG may be co- administered with rifapentine/isoniazid without dose adjustment.
References
Churchyard, G, Savic, R, Gupte, A, Marzinke, M, Zhang, N, Edward, V, etc.. Safety & pk of weekly rifapentine/isoniazid (3hp) in adults with hiv on dolutegravir. Conference On Retroviruses And Opportunistic Infections. 2019; : .
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