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HIV-1 InfectionPhase 3ADVANCENCT03122262

ADVANCE Study of DTG + TAF + FTC vs DTG + TDF + FTC and EFV + TDF+FTC in First-line Antiretroviral Therapy

A Phase 3 study testing Dolutegravir, Tenofovir Alafenamide and Truvada in people with HIV-1 Infection, run by Professor Francois Venter at 4 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a non-inferiority (10% non-inferiority margin), study to assess the efficacy and safety of dolutegravir, DTG (50 mg once daily [QD]) administered in combination with tenofovir alafenamide fumarate, TAF (25 mg QD) and emtricitabine, FTC (200 mg QD) compared to DTG (50 mg QD) administered in combination with… Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
Dolutegravir, Tenofovir Alafenamide and Truvada
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,110 participants
Where
4 sitesSouth Africa
Study dates
16 Jan 2017to 29 Jul 2022
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Age ≥ 12 years and ≥ 40 kg
  • Documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening
  • Plasma HIV-1 RNA (VL) ≥ 500 copies/mL
  • All pre-existing medical or laboratory abnormalities must be deemed to be stable by the investigator prior to study enrolment
  • Calculated creatinine clearance (CrCl) > 60 mL/min (Cockcroft-Gault formula) in > 18 years old OR > 80 mL/min (modified Cockcroft-Gault) in ≤ 18 years old
  • Ability to comprehend the full nature and purpose of the study, in the opinion of the investigator, and to comply with the requirements of the entire study.
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  • To enrol in extension post-96 weeks:
  • Each patient must meet all of the following criteria to be enrolled in this study:
  • Previously enrolled on the ADVANCE study, and followed to week 96 (including those on post-trial access)
  • Ability to comprehend the full nature and purpose of the study, including the extended timeline, in the opinion of the investigator, and to comply with the requirements of the entire study.

Who cannot join

  • Previously received more than 30 days of treatment with any form of antiretroviral therapy (ART) or
  • Received any antiretrovirals within the last 6 months
  • Women who are pregnant at the time of the screening or baseline visit
  • Active tuberculosis and/or are on antituberculous therapy at the time of the baseline visit
  • Taking and cannot discontinue prohibited concomitant medications listed in 7.3 at least 2 weeks prior to the baseline visit and for the duration of the study period
  • Clinically unstable, in the investigator's opinion
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  • Current history of drug or alcohol abuse that, in the opinion of the investigator, may be an impediment to patient adherence to the protocol
  • Patients who participated in a study with an investigational drug within 60 days of screening or who are currently receiving treatment with any other investigational drug or device may be ineligible to participate. This is an investigator decision
  • Have a strong likelihood of relocating far enough to make access to the study site difficult
  • History or presence of allergy to the study drugs or their components
  • Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); Child-Pugh C.
  • To enrol in extension post-96 weeks:
  • Patients meeting the following criteria will be excluded from the study:
  • HbA1c, lipids and blood pressures that are not responding to treatment, in the opinion of the investigator and in consultation with the principal investigator, justifying substitution of DTG or TAF
  • Clinically unstable, in the opinion of the investigator
  • Have a strong likelihood of relocating far enough to make access to the study site difficult.

Trial locations and contacts

4 sites in 1 country.

South Africa4 sites

  • Shandukani Research Centre

    Johannesburg, Gauteng, 2001

  • Charlotte Maxeke Johannesburg Academic Hospital

    Johannesburg, Gauteng, 2196

  • Sunnyside Office Park

    Johannesburg, Gauteng

  • Wits RHI Yeoville Clinic

    Johannesburg, Gauteng

Other trials in South Africa

About this study

Official title: WRHI 060 (ADVANCE): A Randomised, Phase 3 Non-inferiority Study of DTG + TAF + FTC Compared With DTG + TDF + FTC and EFV + TDF + FTC in Patients Infected With HIV-1 Starting First-line Antiretroviral Therapy - Extension to 192 Weeks

This is a non-inferiority (10% non-inferiority margin), study to assess the efficacy and safety of dolutegravir, DTG (50 mg once daily [QD]) administered in combination with tenofovir alafenamide fumarate, TAF (25 mg QD) and emtricitabine, FTC (200 mg QD) compared to DTG (50 mg QD) administered in combination with tenofovir disoproxil fumarate, TDF (300 mg QD) and FTC (200 mg QD) and compared to efavirenz, EFV (600 mg QD) administered in combination with TDF (300 mg QD) and FTC (200 mg QD) through 96 weeks in patients with HIV-1 starting first-line ART.

Read the detailed description

This is an open label randomised, non-inferiority (10% non-inferiority margin), phase 3 study to assess the efficacy and safety of DTG (50 mg once daily [QD]) administered in combination with TAF (25 mg QD) and FTC (200 mg QD) compared to DTG (50 mg QD) administered in combination with TDF (300 mg QD) and FTC (200 mg QD) and compared to EFV (600 mg QD) administered in combination with TDF (300 mg QD) and FTC (200 mg QD) through 96 weeks in patients with HIV-1 starting first-line ART.

Approximately 1110 male and female patients infected with HIV-1 who are eligible for first-line ART will be randomly assigned in a 1:1:1 ratio (approximately 370 patients per treatment group) to Treatment Group 1 (DTG + TAF + FTC) or Treatment Group 2 (DTG + TDF + FTC) or Treatment Group 3 (EFV + TDF + FTC). To ensure adequate representation of adolescents (12 - 18 years) in any treatment group, randomisation will be stratified according to age greater or less than 18 years. The study includes screening and baseline visits, 8 study visits from Week 4 to Week 84, and a preliminary end of study visit at Week 96.

The study will then take patients on Treatment Group 1 (DTG + TAF + FTC) or Treatment Group 2 (DTG + TDF + FTC) or Treatment Group 3 (EFV + TDF + FTC), who have completed 96 weeks successfully, and follow them to 192 weeks, with visits every 24 weeks after enrolment to 192 weeks. Study medication pill counts will be performed at each follow-up visit.

Conditions
HIV-1 Infection
Being tested
Dolutegravir, Tenofovir Alafenamide, Truvada, Atripla
Keywords
Antiretroviral Agents, first-line antiretroviral therapy, dolutegravir, Tenofovir alafenamide

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DolutegravirDrug

    Also called Tivicay

    DTG 50mg Oral Tablet once daily

  • Tenofovir AlafenamideDrug

    Also called Descovy

    TAF/FTC 25/200mg Oral Tablet once daily

  • TruvadaDrug

    Also called TDF/FTC 300/200mg Oral Tablet

  • AtriplaDrug

    Also called EFV/TDF/FTC 600/200/300mg Oral Tablet

Study groups in NCT03122262
Study groupRoleWhat they receive
Tenofovir AlafenamideActive comparatorDescovy: Tenofivir alafenamide tablets 25mg daily, Emtricitabine 200mg daily
Receives: Drug: Dolutegravir; Drug: Tenofovir Alafenamide
DolutegravirActive comparatorDolutegravir 50mg daily, Truvada 500mg daily
Receives: Drug: Dolutegravir; Drug: Truvada
AtriplaActive comparatorAtripla: Efavirenz 600mg daily, Tenofovir Disoproxil Fumarate 300mg daily, Emtricitabine 200mg daily
Receives: Drug: Atripla

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Proportion of patients with undetectable plasma HIV-1 RNA levels (< 50 copies/mL) at Week 48

    The proportion of participants with undetectable plasma HIV-1 RNA levels at Week 48, will be calculated for each treatment group and summarised.

    Measured: 48 weeks

Secondary outcomes (5)

  1. Proportion of patients with undetectable plasma HIV-1 RNA levels (< 50 copies/mL) at Week 48, 96, 144 and 192

    Using FDA snapshot algorithm

    Measured: 192 weeks

  2. Proportion of patients with plasma HIV-1 RNA levels < 200 copies/mL at Week 192

    • Participants with undetectable plasma HIV-1 RNA levels will be defined as those with plasma RNA levels of < 200 copies/mL. Successes/responders will be defined as those participants on each regimen with undetectable plasma HIV-1 RNA levels at Week 192.

    Measured: 192 weeks

  3. Time to virologic failure (defined as confirmed HIV-1 RNA levels ≥ 1000 copies/mL at week 12 - 24 or ≥ 200 copies/mL at or after week 24)

    Time to virologic failure will be modelled by Cox regression.

    Measured: 24 weeks

  4. Change from baseline in plasma HIV-1 RNA levels at each visit

    Individual patient plasma HIV-1 RNA levels will be summarised and listed by treatment and visit, together with changes from screening/enrolment plasma HIV-1 RNA levels. Observations (linear and log transformed) will also be presented graphically, over time, in the form of line plots.

    Measured: At week 12, 24, 36, 60, 72, 84, 96, 120, 144, 168, 192

  5. Change from baseline in plasma CD4 levels at each visit

    Individual patient CD4 counts will be summarised and listed by treatment and visit, together with changes from screening/enrolment CD4 values. Observations (linear and log transformed) will also be presented graphically, over time, in the form of line plots.

    Measured: At week 12, 24, 36, 60, 72, 84, 96, 120, 144, 168, 192

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2017
  2. Study start16 Jan 2017
  3. Primary completion30 Apr 2022
  4. Study completion29 Jul 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03122262
Sponsor's protocol ID
WRHI060
Acronym
ADVANCE
Status last verified
Feb 2023
First submitted
11 Oct 2016
Last updated
8 Feb 2023
Results posted
No
Data monitoring committee
Yes
Individual data sharing
Yes: The data that will be shared is all of the individual participant data collected during the trial, after deidentification.

Publications

  • Manne-Goehler J, Fabian J, Sokhela S, Akpomiemie G, Rahim N, Lalla-Edward ST, Brennan AT, Siedner MJ, Hill A, Venter WDF. Blood pressure increases are associated with weight gain and not antiretroviral regimen or kidney function: a secondary analysis from the ADVANCE trial in South Africa. J Int AIDS Soc. 2024 Jul;27(7):e26268. doi: 10.1002/jia2.26268.

    PubMed 38978403

  • Cindi Z, Kawuma AN, Maartens G, Bradford Y, Sokhela S, Chandiwana N, Venter WDF, Wasmann RE, Denti P, Wiesner L, Ritchie MD, Haas DW, Sinxadi P. Pharmacogenetics of tenofovir clearance among Southern Africans living with HIV. Pharmacogenet Genomics. 2023 Jun 1;33(4):79-87. doi: 10.1097/FPC.0000000000000495. Epub 2023 Mar 6.

    PubMed 37098852

  • Cindi Z, Maartens G, Bradford Y, Venter WDF, Sokhela S, Chandiwana NC, Haas DW, Sinxadi P. Genetic Associations with Weight Gain among South Africans who Initiated Dolutegravir-Containing and Tenofovir-Containing Regimens. J Acquir Immune Defic Syndr. 2021 Jul 1;87(3):1002-1009. doi: 10.1097/QAI.0000000000002661.

    PubMed 33625064

  • Siedner MJ, Moorhouse MA, Simmons B, de Oliveira T, Lessells R, Giandhari J, Kemp SA, Chimukangara B, Akpomiemie G, Serenata CM, Venter WDF, Hill A, Gupta RK. Reduced efficacy of HIV-1 integrase inhibitors in patients with drug resistance mutations in reverse transcriptase. Nat Commun. 2020 Dec 1;11(1):5922. doi: 10.1038/s41467-020-19801-x.

    PubMed 33262331

  • Venter WDF, Sokhela S, Simmons B, Moorhouse M, Fairlie L, Mashabane N, Serenata C, Akpomiemie G, Masenya M, Qavi A, Chandiwana N, McCann K, Norris S, Chersich M, Maartens G, Lalla-Edward S, Vos A, Clayden P, Abrams E, Arulappan N, Hill A. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. Lancet HIV. 2020 Oct;7(10):e666-e676. doi: 10.1016/S2352-3018(20)30241-1.

    PubMed 33010240

  • Venter WDF, Moorhouse M, Sokhela S, Fairlie L, Mashabane N, Masenya M, Serenata C, Akpomiemie G, Qavi A, Chandiwana N, Norris S, Chersich M, Clayden P, Abrams E, Arulappan N, Vos A, McCann K, Simmons B, Hill A. Dolutegravir plus Two Different Prodrugs of Tenofovir to Treat HIV. N Engl J Med. 2019 Aug 29;381(9):803-815. doi: 10.1056/NEJMoa1902824. Epub 2019 Jul 24.

    PubMed 31339677

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dolutegravir, Tenofovir Alafenamide and Truvada in people with HIV-1 Infection, run by Professor Francois Venter at 4 sites in South Africa.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of patients with undetectable plasma HIV-1 RNA levels (< 50 copies/mL) at Week 48 (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03122262, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.

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