Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Adults Aged ≥ 60 Years

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the safety of elvitegravir/cobicistat/emtricitabine/ tenofovir alafenamide (E/C/F/TAF) relative to unchanged current antiretroviral therapy (ART) by assessing spine and hip bone mineral density (BMD) measured at Week 48 in virologically-suppressed, HIV-1 infected participants aged ≥ 60 years.

Official Title
-----------------
A Phase 3b, Randomized, Open-Label Study to Evaluate Switching From a Tenofovir Disoproxil Fumarate (TDF) Containing Regimen to Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Alafenamide (E/C/F/TAF) Fixed-Dose Combination (FDC) in Virologically-Suppressed, HIV-1 Infected Subjects Aged ≥ 60 Years

Conditions
-----------------
HIV-1 Infection

Intervention / Treatment
-----------------
* Drug: E/C/F/TAF
* Drug: TDF
* Drug: FTC
* Drug: FTC/TDF
* Drug: 3TC
* Drug: Third agent


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Currently receiving a TDF and FTC or 3TC-containing 'backbone' (maximum 2 NRTIs) regimen plus a third agent for ≥ 6 consecutive months prior to screening visit. For individuals with 3 or more ART regimens, a regimen history must be provided for approval by the Sponsor. Refer to assigned interventions for allowed third agents of the current regimen. Documented plasma HIV-1 RNA levels < 50 copies/mL for ≥ 6 months preceding the screening visit (measured at least twice using the same assay). In the preceding 6 months prior to screening, one episode of blip (HIV-1 RNA > 50 and < 400 copies/mL) is acceptable, only if HIV-1 RNA is < 50 copies/mL immediately before and after the blip. Plasma HIV-1 RNA level < 50 copies/mL at screening visit Adequate renal function Estimated glomerular filtration rate ≥ 30 mL/min according to the Cockcroft-Gault formula (eGFRCG) and are on ARVs that are appropriately dose adjusted for renal function per package insert All documented historical plasma genotype(s) must not show resistance to TDF or FTC, including, but not limited to the presence of reverse transcriptase resistance mutations K65R, K70E, M184V/I, or thymidine analog-associated mutations (TAMs) that include M41L, L210W, D67N, K70R, T215Y/F, K219Q/E/N/R. If historical plasma prior to first ART is not available or individual has 3 or more ART regimens, individuals will have proviral genotype analysis prior to Day 1 to confirm absence of archived resistance to TDF or FTC. Study performed dual energy x-ray absorptiometry (DXA) scan and T-score received prior to Day 1 Key Exclusion Criteria: Previous use of any approved or experimental integrase strand transfer inhibitor (INSTI) (for any length of time) if the current regimen contains a PI/r Individuals will have no evidence of previous virologic failure on a PI/r or INSTI-based regimen (with or without resistance to either class of ARV) A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4+ cell count and/or percentage criteria) Hepatitis C virus that would require therapy during the study Individuals receiving ongoing treatment for bone disease (eg, osteoporosis), including bisphosphonates, denosumab, and strontium ranelate Note: Other protocol defined Inclusion/ Exclusion criteria may apply.

Ages Eligible for Study
-----------------
Minimum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E/C/F/TAF<br>Participants will switch from tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) or 3TC plus a third agent to E/C/F/TAF and will receive treatment for 48 weeks. | Drug: E/C/F/TAF<br>* 150/150/200/10 mg FDC tablet administered orally once daily<br>* Other names: Genvoya®;|
| Active Comparator: Remain current regimen<br>Participants will remain on current TDF and FTC (or FTC/TDF) or 3TC plus continuing third agent. | Drug: TDF<br>* 300 mg tablet administered orally once daily<br>* Other names: Viread®;Drug: FTC<br>* 200 mg capsule administered orally once daily<br>* Other names: Emtriva®;Drug: FTC/TDF<br>* 200/300 mg tablet administered orally once daily<br>* Other names: Truvada®;Drug: 3TC<br>* Tablet administered orally<br>* Other names: Epivir®;Drug: Third agent<br>* Third agent may include one of the following regimens: lopinavir+ritonavir (LPV/r; Kaletra®), atazanavir (ATV; Reyataz®) + ritonavir (RTV; Norvir®), ATV + cobicistat (COBI;Tybost®) (or ATV/COBI FDC), DRV + RTV, darunavir (DRV; Prezista®) + COBI (or DRV/COBI FDC), fosamprenavir (FPV; Lexiva®) + RTV , saquinavir (SQV; Invirase®; Fortovase®) + RTV, efavirenz (EFV;Sustiva®), rilpivirine (RPV;Edurant®), nevirapine (NVP;Viramune®), etravirine (ETR;Intelence®), raltegravir (RAL; Isentress®), elvitegravir (EVG) + COBI, or dolutegravir (DTG;Tivicay®) Drug classes: Protease inhibitors (PI): LPV/r, ATV, RTV, ATV, DRV, FPV, and SQV Pharmacokinetic enhancer: COBI Non-nucleoside reverse transcriptase inhibitors (NNRTI): EFV, RPV, NVP, and ETR Integrase inhibitors: RAL and DTG<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 48 in Spine BMD |  | Baseline; Week 48 | 
| Percent Change From Baseline to Week 48 in Hip BMD |  | Baseline; Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline to Week 24 in Spine BMD |  | Baseline; Week 24 | 
| Percent Change From Baseline to Week 24 in Hip BMD |  | Baseline; Week 24 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 24 | 
| Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm | The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a participant's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status. | Week 48 | 
| Change From Baseline in CD4+ Cell Count at Week 24 |  | Baseline; Week 24 | 
| Change in Baseline in CD4+ Cell Count at Week 48 |  | Baseline; Week 48 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV 1 Infection, HIV, Virologically-Suppressed