Safety, Tolerability, and Drug-drug Interactions of Short-course Treatment of Latent Tuberculosis Infection With High-dose Rifapentine and Isoniazid or Standard Isoniazid Preventative Therapy Among HIV-infected Patients Taking Dolutegravir-based Antiretroviral Treatment

3HP DTG AUR1-6-212 IMPAACT4TB

Single-arm, single-center, Phase I/II clinical trial, in four groups. Individuals with HIV infection taking Efavirenz (EFV) and two nucleoside reverse transcriptase inhibitors (NRTI) who have undetectable (Groups 1 and 2) or detectable (Group 3 and 4) HIV viral load and an indication for TPT, will be switched to DTG with tenofovir/emtricitabine (Groups 1 and 2) or lamivudine/tenofovir (Groups 3 and 4). Group 1 and 2 will receive weekly HP for 12 total doses starting 8 weeks after initiating DTG. Individuals who are on an existing DTG-based plus two NRTI ART regimen for at least eight weeks (and have not received efavirenz or nevirapine for at least two months) who have an undetectable HIV viral load may also participate. Individuals with HIV infection who are ART treatment naïve at any HIV viral load level and have an indication for TPT will start DTG and be enrolled to receive standard IPT (Group 3) or HP (Group 4) initiated at the same time as DTG. Group 3 and 4 will be enrolled after follow up of Group 1 and 2 has been completed.

2018-01-18

2022-12-07

2022-12-07

Completed

Early phase I

135

Inclusion Criteria: 1. Age \> 18 years 2. Weight \> 50 kg 3. Documented HIV infection\* 4. At least 8 weeks of HIV treatment with efavirenz or dolutegravir plus two NRTI, or ART treatment naïve, depending upon the enrolling treatment Group 5. Undetectable or detectable HIV-1 viral load, depending upon the enrolling treatment Group Exclusion Criteria: 1. Confirmed or suspected TB disease 2. Likely to move from the study area during the study period 3. Known exposure to TB cases with known or suspected resistance to isoniazid or rifampicin in the source case 4. TB treatment within the past year 5. TB preventive therapy within the last year 6. Sensitivity or intolerance to isoniazid or rifamycins 7. On nevirapine, etravirine, rilpivirine, PI-based, or raltegravir-containing ART regimens 8. Suspected acute hepatitis or known chronic liver disease; severe hepatic impairment (Class C or greater) as determined by Child Pugh classification 9. ALT≥ 3 times the upper limit of normal (ULN) 10. Total bilirubin ≥ 2.5 times the ULN 11. Absolute neutrophil count (ANC) ≤ 750 cells/mm3 12. Creatinine clearance \< 50 ml/min 13. Pregnancy or breastfeeding 14. Women of childbearing potential who are unable or unwilling to use contraception 15. Self-reported alcohol use exceeding 28 units per week for men, or 21 units for women 16. Karnofsky status \< 80 17. On prohibited medications e.g. dofetilide (see Appendix 1) 18. Known porphyria

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Group 1A:12 ppts will take DTG 50mg/TDF/FTC once daily + once weekly HP for 12 weeks. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.An interim PK, safety,and HIV VL assessment will be performed to ensure that DTG 50mg once daily is safe and meets PK targets.Group 1B:18 ppts will receive either DTG 50mg or dose adjusted DTG + once weekly HP. Semi-intensive PK for DTG,RPT,INH will be collected per protocol.Group 2: 30 ppts will receive DTG at the same dose and frequency as Group 1B. Sparse PK for DTG, safety labs and HIV VL will be measured per protocol.Group 3: 25 ppts who are HIV tx naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + standard of care isoniazid preventive therapy. ART and IPT will start together. Sparse PK for DTG will be collected per protocol.Group 4: 50 ppts who are HIV treatment naive will start DTG 50mg/TDF/3TC daily as a FDC tablet + weekly HP for 12 weeks. ART and 3HP will start together. Sparse PK for DTG will be collected per protocol.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 135, 'type': 'ACTUAL'}}

2023-02-02