Clinical trial NCT03727152: Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir
Official title: Maintenance of Switching From Protease Inhibitor/Ritonavir to Generic Single Tablet Regimen of Tenofovir Alafenamide/Emtricitibine/Dolutegravir in Virologically Suppressed HIV-infected Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Keywords: generic TAF/E/D
virologically suppressed HIV-infected adults
pharmacokinetics (PK) parameters of DTG
psychiatric symptoms
metabolic syndrome
ASCVD risk
liver fibrosis
Lead sponsor: The HIV Netherlands Australia Thailand Research Collaboration
Sponsor class: OTHER
Collaborators: name: Faculty of Medical Sciences, Radboud University of Medical Center
name: Department of Pharmaceutical care, Faculty of Pharmacy, Chiang Mai University
name: Police General Hospital
First posted: 2018-11-01
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase III, multicenter, open-label, single-arm study of 190 virologically suppressed HIV-infected adults

Detailed description: The fundamental principle of regimen switching is to maintain viral suppression without jeopardizing future treatment options. The reasons to consider regimen switching in the viral suppressed population are to simplify the regimen by reducing the pill burden and dosing frequency, to increase the tolerability, reduce the adverse effects as well as long-term toxicities, to prevent drug-to-drug interactions and to avoid the dietary requirements.

Generic TAF/E/D (tenofovir alafenamide 25mg/emtricitabine 200mg/dolutegravir 50 mg), a single-tablet once daily regimen, will be an affordable regimen with the potential characteristics such as reduced pill burden, less drug to drug interaction and toxicities. The generic form (Mylan) is recently received the tentative approval from the U.S. Food and Drug Administration (FDA) under the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Whether DTG-containing regimen is a better option than protease inhibitors among resource-limited settings during the decisions for second-line treatment options, is needed to be evaluated.

All participants will be switched from their pre-study ART regimen to a single tablet regimen (STR) of TAF/FTC/DTG 25/200/50mg once daily.

Eligibility criteria: Inclusion Criteria:

1. Documented HIV-1 infection
2. Aged ≥18 years old
3. Female participant may be eligible to participate if she:

   is of non-childbearing potential defined as either post-menopausal (12 months of spontaneous amenorrhea or \>=54 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy, or bilateral oophorectomy or, is of child-bearing potential, with a negative pregnancy test at both Screening and week 0 and agrees to use one of the protocol-defined methods of contraception to avoid pregnancy.
4. On current ART for at least 6 months prior to study entry
5. Current ART includes boosted protease inhibitors
6. No more than one HIV-1 plasma RNA \>50 copies/mL and \<200 copies/L (only one 'blip') in the past 6 months with a subsequent HIV-1 plasma RNA \<50 copies/mL
7. HIV-1 plasma RNA \<50 copies/mL at screening visit
8. No prior or current exposure to integrase strand transfer inhibitor (INSTI)
9. Have signed the informed consent form

Exclusion Criteria:

1. Breastfeeding female
2. Pregnancy or positive UPT at screening
3. Calculated creatinine clearance as estimated by Cockcroft-Gault equation (CrCl) \<60 mL/min,
4. Alanine aminotransferase (ALT) \>2.5 x ULN,
5. Concomitant use of any of the following medications:

(1) aluminum and magnesium-containing antacids, proton-pump inhibitors (2) anticonvulsants: carbamazepine, oxcarbamazepine, phenobarbital, phenytoin (3) antimycobacterials: rifabutin, rifampin, rifapentine (4) St. John's wort

6. Alcohol or drug abuse that, in the opinion of the investigator, would interfere with completion of study procedures

7. Any serious illness that, in the opinion of the investigator, would interfere with completion of study procedures

Primary outcomes:
measure: number of subjects with undetectable viral load
timeFrame: 48 weeks
Secondary outcomes:
measure: Proportion of participants without tolerability failure
timeFrame: weeks 24 and weeks 48
measure: Cmax of DTG
timeFrame: weeks 24 and weeks 48
measure: Tmax of DTG
timeFrame: weeks 24 and weeks 48
measure: AUC of DTG
timeFrame: weeks 24 and weeks 48
measure: T1/2 of DTG
timeFrame: weeks 24 and weeks 48
measure: Ke of DTG
timeFrame: weeks 24 and weeks 48
measure: CL of DTG
timeFrame: weeks 24 and weeks 48
measure: Anxiety at baseline will be compared to level of anxiety at weeks 24 and weeks 48.
timeFrame: weeks 24 and weeks 48
measure: Depression at baseline will be compared to depression level at weeks 24 and weeks 48.
timeFrame: weeks 24 and weeks 48
measure: Changes from baseline in fasting lipid profiles
timeFrame: weeks 24 and weeks 48
measure: Changes from baseline in insulin
timeFrame: weeks 24 and weeks 48
measure: Changes from baseline in fasting blood glucose levels
timeFrame: weeks 24 and weeks 48
measure: Changes from baseline in renal parameters (creatinine, eGFR)
timeFrame: weeks 24 and weeks 48
measure: Changes from baseline in transient elastography results
timeFrame: weeks 24 and weeks 48
Other outcomes:
Locations:
city: Bangkok
country: Thailand
facility: HIV-NAT, Thai Red Cross AIDS Research Centre
city: Bangkok
country: Thailand
facility: Police General Hospital
Study officials:
affiliation: The HIV Netherlands Australia Thailand Research Collaboration
name: Sivaporn Gatechompol, MD
role: PRINCIPAL_INVESTIGATOR
References: