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CompletedNCT03122262ADVANCEUpdated Feb 8, 2023

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

A Phase 3 interventional study of Dolutegravir and Tenofovir Alafenamide in HIV-1 Infection, sponsored by Professor Francois Venter. Completed at 4 sites in South Africa. Open to participants aged 12 Years and older. Per ClinicalTrials.gov, last updated 2023-02-08.

Sponsored by Professor Francois Venter · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
1,110
Allocation
Randomized
Ages
12 Years and older
Sex
All
01

Study 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 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.

02

Conditions studied

  • HIV-1 Infection

Keywords

  • Antiretroviral Agents, first-line antiretroviral therapy
  • dolutegravir
  • Tenofovir alafenamide
03

In context

Lead sponsor

Professor Francois Venter is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Age ≥ 12 years and ≥ 40 kg
  2. Documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening
  3. Plasma HIV-1 RNA (VL) ≥ 500 copies/mL
  4. All pre-existing medical or laboratory abnormalities must be deemed to be stable by the investigator prior to study enrolment
  5. 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
  6. 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.

To enrol in extension post-96 weeks:

Each patient must meet all of the following criteria to be enrolled in this study:

  1. Previously enrolled on the ADVANCE study, and followed to week 96 (including those on post-trial access)
  2. 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.

Exclusion criteria

Exclusion Criteria:

  1. Previously received more than 30 days of treatment with any form of antiretroviral therapy (ART) or
  2. Received any antiretrovirals within the last 6 months
  3. Women who are pregnant at the time of the screening or baseline visit
  4. Active tuberculosis and/or are on antituberculous therapy at the time of the baseline visit
  5. 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
  6. Clinically unstable, in the investigator's opinion
  7. Current history of drug or alcohol abuse that, in the opinion of the investigator, may be an impediment to patient adherence to the protocol
  8. 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
  9. Have a strong likelihood of relocating far enough to make access to the study site difficult
  10. History or presence of allergy to the study drugs or their components
  11. 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:

  1. 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
  2. Clinically unstable, in the opinion of the investigator
  3. Have a strong likelihood of relocating far enough to make access to the study site difficult.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
1,110 participants (actual)

Study arms

  • Active comparator
    Tenofovir Alafenamide

    Descovy: Tenofivir alafenamide tablets 25mg daily, Emtricitabine 200mg daily

    Drug: Dolutegravir · Drug: Tenofovir Alafenamide

  • Active comparator
    Dolutegravir

    Dolutegravir 50mg daily, Truvada 500mg daily

    Drug: Dolutegravir · Drug: Truvada

  • Active comparator
    Atripla

    Atripla: Efavirenz 600mg daily, Tenofovir Disoproxil Fumarate 300mg daily, Emtricitabine 200mg daily

    Drug: Atripla

Interventions

  • DrugDolutegravir

    DTG 50mg Oral Tablet once daily

    Also known as: Tivicay

  • DrugTenofovir Alafenamide

    TAF/FTC 25/200mg Oral Tablet once daily

    Also known as: Descovy

  • DrugTruvada

    Also known as: TDF/FTC 300/200mg Oral Tablet

  • DrugAtripla

    Also known as: EFV/TDF/FTC 600/200/300mg Oral Tablet

06

What researchers measure

Primary outcomes

  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.

    Time frame: 48 weeks

Secondary outcomes

  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

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

    Time frame: 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.

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

Other outcomes

  1. Nature and frequency of adverse events

    A summary table will be presented, summarised by treatment, SOC and preferred term including the number of patients dosed in treatment group and number and percentage of subjects with AEs.

    Time frame: Week 48, 96, 144, 192

  2. Analysis of PK data in those developing TB

    Participants in treatment groups 1 and 2 who develop TB during the study will have DTG trough levels (ng/mL) measured at routine scheduled three visits. Trough levels will also be measured in control subjects (without TB coinfection) in a 3:1 ratio.

    Time frame: Over course of TB treatment in those developing TB, during 3 regular scheduled visits

  3. Analysis of PK data in those becoming pregnant

    Participants in treatment groups 1 and 2 who develop TB during the study will have DTG trough levels (ng/mL) measures will be measured in control non-pregnantsubjects in a 3:1 ratio.

    Time frame: Monthly

  4. Virological efficacy in the 12 - 18 year age group

    Proportion of patients with undetectable plasma HIV-1 RNA levels (\< 50 copies/mL) at Week 48 and 96 in a subgroup analysis of this age-range

    Time frame: Week 48, 96

07

Study locations

4 sites
  • Shandukani Research Centre
    Johannesburg, Gauteng 2001, South Africa
  • Charlotte Maxeke Johannesburg Academic Hospital
    Johannesburg, Gauteng 2196, South Africa
  • Sunnyside Office Park
    Johannesburg, Gauteng, South Africa
  • Wits RHI Yeoville Clinic
    Johannesburg, Gauteng, South Africa
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References and documents

Publications

  • 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 ↗

Individual participant data

Plan to share: Yes — The data that will be shared is all of the individual participant data collected during the trial, after deidentification.

Supporting information: Study protocol, Icf

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 8, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT03122262
Lead sponsor
Professor Francois Venter
Responsible party
Professor Francois Venter (Professor, University of Witwatersrand, South Africa) — Sponsor-investigator
First posted
Apr 20, 2017
Start date
Jan 16, 2017
Primary completion
Apr 30, 2022
Completion
Jul 29, 2022
Last update
Feb 8, 2023

Study contacts

Willem Daniel Francois Venter, FCP (SA)
principal investigator · Wits Reproductive Health & HIV Institute, University of the Witswatersrand

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2023. You cannot join it, but the record below documents what was studied.

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