NCT02815566

Brief Summary

Design: Open-label randomised multicenter international strategic trial of older women on combination antiretroviral therapy (cART) containing tenofovir-emtricitabine (TDF/FTC) with HIV RNA suppression for \> 6 months to : 1. Immediate switch of TDF/FTC to tenofovir alafenamide-emtricitabine (TAF/FTC) while continuing the third antiretroviral agent.; 2. Delayed switch; with switch of TDF/FTC to TAF/FTC at 48 weeks while continuing the third agent. Follow up of all subjects to 96 weeks. Subject Population: The anticipated sample size is 128 HIV infected women aged 45-55 years (peri or early post menopause). . Primary endpoint: Percentage change from baseline bone mineral density (BMD) at the lumbar spine at weeks 48 and 96. Secondary Endpoints: BMD change at hip, trabecular bone score, estimated bone strength by high resolution peripheral quantitative computerized tomography (HR-pQCT), muscle quality, geriatric assessment; biomarkers of bone, immune activation and inflammation; HIV viral suppression; safety, lipid and renal function, cardiovascular risk scores at weeks 48 and 96. Expected Outcomes: To determine if a switch from TDF/FTC to TAF?FTC improves BMD to a degree correlating with a decreased risk of fragility fracture in aging HIV infected women. Secondary outcomes will assess bone strength using new imaging modalities, timing of switch, and renal health. This data will be used by health policy makers and providers to determine the proper use of TAF/FTC in the aging HIV population.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Sep 2017

Longer than P75 for phase_4

Geographic Reach
2 countries

7 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 22, 2016

Completed
6 days until next milestone

First Posted

Study publicly available on registry

June 28, 2016

Completed
1.2 years until next milestone

Study Start

First participant enrolled

September 12, 2017

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 25, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 25, 2021

Completed
1.9 years until next milestone

Results Posted

Study results publicly available

January 19, 2023

Completed
Last Updated

December 19, 2024

Status Verified

December 1, 2024

Enrollment Period

3.5 years

First QC Date

June 22, 2016

Results QC Date

September 27, 2022

Last Update Submit

December 3, 2024

Conditions

OsteoporosisHIVMenopause

Keywords

kidney, antiretroviral agent, tenofovir, osteoporosis, women

Outcome Measures

Primary Outcomes (1)

  • Percent Change in Bone Mineral Density From Baseline at the Lumbar Spine

    The outcome measures presented are descriptive as enrollment in the clinical trial did not reach the target number of subjects needed to achieve target power and was insufficient to produce statistically reliable results. There are limited results at the week 48 timepoint due to the COVID pandemic.

    Baseline, 48 weeks and 96 weeks

Secondary Outcomes (1)

  • % Change in Bone Mineral Density From Baseline at the Femoral Neck

    Baseline, 48 weeks and 96 weeks

Study Arms (2)

Immediate switch

EXPERIMENTAL

Open label tenofovir-alafenamide (25/10mg)-emtricitabine (200mg) tablet once daily by mouth for 96 weeks

Drug: tenofovir-alafenamide-emtricitabine

delayed switch

ACTIVE COMPARATOR

Open-label tenofovir (300mg)-emtricitabine (200mg) tablet once daily by mouth for 48 weeks followed by open label tenofovir-alafenamide (25/10mg)-emtricitabine (200mg) tablet once daily by mouth for an additional 48 weeks

Drug: tenofovir-emtricitabine

Interventions

tenofovir-alafenamide-emtricitabineDRUG

comparison of tenofovir-emtricitabine and tenofovir-alafenamide-emtricitabine on bone mineral density

Also known as: Descovy
Immediate switch
tenofovir-emtricitabineDRUG

comparison of tenofovir-emtricitabine and tenofovir-alafenamide-emtricitabine on bone mineral density

Also known as: Truvada
delayed switch

Eligibility Criteria

Age40 Years - 60 Years
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Biological female aged 40-60
  • Documented HIV-1 infection
  • Peri-menopausal ( as documented by history).
  • Signed Informed Consent Form and willing to comply with the protocol.
  • Receiving a cART regimen containing a ritonavir boosted PI (darunavir, atazanavir, lopinavir,) or an NNRTI (efavirenz, nevirapine or rilpivirine) or an integrase inhibitor (dolutegravir or raltegravir or elvitegravir) in combination with TDF-FTC for \> 24 weeks.
  • Stable viral suppression (plasma HIV-RNA\<50 copies/mL for \> 24 weeks). Single viral blip \<500/ml allowed if re-suppresses.
  • If of childbearing potential, is using effective birth control methods and is willing to continue during the trial.
  • Women will be assessed for vitamin D and calcium dietary intake; if inadequate for age, supplements will be recommended.

You may not qualify if:

  • HIV-2
  • High 10-year fracture risk at baseline ( \> 20%) based on country specific FRAX
  • Current treatment with active bone medications- bisphosphonates, denosumab, calcitonin, raloxifene, teriparatide, strontium
  • Current use of systemic steroids ( inhaled steroids permitted) or chemotherapeutic agents
  • Acute viral hepatitis
  • Chronic hepatitis C with liver transaminases \>5 x ULN or expected to require treatment for hepatitis C during the trial period.
  • Any investigational ARV within 30 days.
  • Dialysis or renal insufficiency (creatinine clearance \< 50ml/min)
  • History of decompensated liver disease (AST or ALT≥5x the upper limit of normal (ULN) or ALT ≥ 3 x ULN and bilirubin ≥ 1.5 x ULN with \> 35% direct bilirubin), or the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices.
  • Pregnant or breastfeeding
  • Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 amylase, creatinine phosphokinase, or lipid elevation.
  • Any condition (including illicit drug use or alcohol abuse) or lab results which, in the investigator's opinion, interfere with assessments or completion of the trial.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (7)

Vancouver ID Research and Care Centre

Vancouver, British Columbia, V6Z 2C7, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8S 1A4, Canada

Location

University Health Network

Toronto, Ontario, M5G 2C4, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

CHU de Québec-Université Laval

Québec, Quebec, G1V 4G2, Canada

Location

Ospedale San Raffaele

Milan, 20127, Italy

Location

Università degli Studi di Modena e Reggio Emilia

Modena, 41124, Italy

Location

Related Publications (1)

  • Walmsley S, Clarke R, Lee T, Singer J, Cheung AM, Smaill F, De Pokomandy A, Trottier S, Messina E, Guaraldi G. BEING: Bone Health in Aging Women with HIV: Impact of Switching Antiretroviral Therapy on Bone Mineral Density During the Perimenopausal Period. AIDS Res Hum Retroviruses. 2023 Apr;39(4):204-210. doi: 10.1089/AID.2022.0106. Epub 2023 Jan 20.

    PMID: 36511389RESULT

MeSH Terms

Conditions

Osteoporosis

Interventions

emtricitabine tenofovir alafenamideEmtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

TenofovirOrganophosphonatesOrganophosphorus CompoundsOrganic ChemicalsEmtricitabineDeoxycytidineCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsAdeninePurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingDeoxyribonucleosidesNucleosidesNucleic Acids, Nucleotides, and NucleosidesDrug CombinationsPharmaceutical Preparations

Limitations and Caveats

Enrollment was a challenge and did not reach the target subject number and was insufficient to produce statistically reliable results. This was primarily due to long delays in study start-up associated with contract negotiations. During the delays, most eligible participants switched to a TAF based regimen outside of the study. The COVID pandemic prevented enrollment of additional participants. The study was closed to futility on the recommendation of the DSMB

Results Point of Contact

Title
Dr. Sharon Walmsley
Organization
University Health Network
sharon.walmsley@uhn.ca
416-340-3871

Study Officials

  • sharon walmsley, MD

    University Health Network, Toronto

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Medicine

Study Record Dates

First Submitted

June 22, 2016

First Posted

June 28, 2016

Study Start

September 12, 2017

Primary Completion

February 25, 2021

Study Completion

February 25, 2021

Last Updated

December 19, 2024

Results First Posted

January 19, 2023

Record last verified: 2024-12

Data Sharing

IPD Sharing
Will share

Information on viral load, toxicity and bone scans will be available to treating physicians

Locations

IT(2)CA(5)