Dolutegravir + Rifapentine/Isoniazid = Unknown or no reaction

Effect on Concentration

Dolutegravir
Decrease
Applies within class?
No
Rifapentine/Isoniazid
No change
Applies within class?
No

Pharmacologic Effects

Dolutegravir
Effect
N/A
Applies within class?
No
Rifapentine/Isoniazid
Effect
N/A
Applies within class?
No

Interaction History

N/A

Last Updated 24-Apr-2019

Summary

Sources

Dolutegravir vs Rifapentine/Isoniazid ^

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 3HP; after 3HP 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 HP. An independent Study Monitoring Committee recommended release of results following its second review.

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 HP doses at the time of this report. Three Grade 3 AE occurred (2 elevated creatinine, 1 hypertension). HIV viral loads at baseline, day 58 (pre-HP), day 72 (3rd HP dose) and day 168 (post-HP) were all <40 c/mL. Table 1 shows Group 1A and 1B PK results. The geometric mean (GM) trough concentration of DTG on Day 58 (pre-HP) was 1003 ug/mL (5th-95th %ile: 500-2080), and during HP treatment 546 (134-1616) with all trough levels but one above DTG IC90 of 64 ug/mL; Table). Overall, HP administration decreased DTG bioavailability by 29% (RSE 13%) (+18%, -37% and -35% for week 1, 3 and 8), while clearance remained unchanged.

Study Conclusions

Co-administration of DTG and HP was well-tolerated, with no HP-related Grade >3 AEs. Although HP 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.

References

Dooley KE, Churchyard G, Savic RM, Gupte A, Markinze MA. Safety & pk of weekly rifapentine/isoniazid (3hp) in adults with hiv on dolutegravir. Conference On Retroviruses And Opportunistic Infections. Seattle, WA. 2019; March 2019.