HIV-1-infectionPhase 4NCT04311957
Continuation of Protease-Inhibitor Based Second-Line Therapy vs. Switch to B/F/TAF in Virologically Suppressed Adults
A Phase 4 study testing Continuation of boosted PI and B/F/TAF in people with HIV-1-infection and Antiretroviral Therapy, run by Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic at 1 site in Haiti.
Trial summary
This randomized trial compares the efficacy of switching to a fixed-dose combination of B/F/TAF versus continuing a boosted protease inhibitor (bPI) regimen in HIV-1 infected participants who are virologically suppressed (HIV-1 RNA <200 copies) on a second-line bPI regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV-1-infection, Antiretroviral Therapy
- What is being tested?
- Continuation of boosted PI and B/F/TAF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 386 participants
- Where
- 1 siteHaiti
- Study dates
- 1 Sep 2020to 30 Nov 2022
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The ability and willingness to give informed consent.
- Age ≥18 years
- History of meeting WHO criteria for immunologic or virologic failure after receipt of a first-line treatment regimen for ≥6 months
- Currently receiving a second-line ART regimen including either ATVr or LPVr + 2 NRTIs for ≥6 months
- At least one HIV-1 RNA <200 copies/mL within 12 months prior to enrollment, and no HIV-1 RNA of at least 200 copies/mL during this period.
- Plasma HIV-1 RNA <200 copies/mL at Screening Visit.
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- eGFR ≥ 50 mL/min according to the MDRD study equation for creatinine clearance
- Hepatic transaminases (AST and ALT) </=5X upper limit of normal (ULN)
- No active TB
- Women of childbearing age must agree to take reliable contraception
Who cannot join
- Active World Health Organization Stage 3 or 4 condition
- Treatment with an INSTI in the past
- Gap in care of at least one month in the prior six months
- Current alcohol or substance use judged by investigator to potentially interfere with participant study compliance
- History of poor adherence, that in the opinion of the investigator, would potentially interfere with study compliance
- Pregnant or breastfeeding at screening visit
- Planning to transfer care
Trial locations and contacts
1 site in 1 country.
Haiti1 site
GHESKIO
Port-au-Prince
Patrice Severe, MD, 3448-5963, patsevere@gheskio.org
Samuel Pierre, MD, 3740-7711, spierre@gheskio.org
About this study
Official title: A Randomized Non-Inferiority Trial to Compare the Efficacy of Switching From Protease-Inhibitor Based Second-Line Therapy to Bictegravir-Tenofovir Alafenamide-Emtricitabine in Virologically Suppressed Adults in Haiti
This randomized trial compares the efficacy of switching to a fixed-dose combination of B/F/TAF versus continuing a boosted protease inhibitor (bPI) regimen in HIV-1 infected participants who are virologically suppressed (HIV-1 RNA <200 copies) on a second-line bPI regimen. Half of participants will receive B/F/TAF and half will continue a bPI regimen. The hypothesize is that B/F/TAF will have efficacy that is non-inferior to the boosted PI regimen.
Read the detailed description
The second generation integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) and bictegravir (BIC) are widely prescribed for the treatment of HIV, due to their favorable tolerability and toxicity profile, durable efficacy, and high barrier to resistance. However, there are limited data to guide the management of patients who are already virally suppressed on a second-line bPI regimen.
Though bPIs have a high barrier to resistance and durable virologic efficacy, they have several important drug-drug interactions, are associated with unfavorable long-term metabolic effects, and may be poorly tolerated. For these reasons, a second-generation INSTI would be preferable to a boosted PI regimen, as long INSTIs are demonstrated to have non-inferior efficacy for patients who are already suppressed on a second-line bPI regimen.
In the proposed study, the efficacy of continuing the bPI regimen will be compared to switching to B/F/TAF.
- Conditions
- HIV-1-infection, Antiretroviral Therapy
- Being tested
- Continuation of boosted PI, B/F/TAF
- Keywords
- HIV, Second-line therapy, Integrase strand transfer inhibitor, Protease inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Continuation of boosted PIDrug
Continuation of the same second-line regimen taken prior to entry:
LPVr 400 mg/100 mg BID or ATVr 300 mg/100 mg QD + 2 NRTIs
B/F/TAFDrug
Single-tablet, fixed dose combination of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily.
| Study group | Role | What they receive |
|---|---|---|
| Boosted PI Group | Active comparator | Continuation of the same second-line regimen taken prior to entry:
This includes either Lopinavir/ritonavir (LPVr) 400 mg/100 mg BID or Atazanavir/ritonavir (ATV/r) 300 mg/100 mg QD
plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). Receives: Drug: Continuation of boosted PI |
| B/F/TAF Group | Experimental | Combination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily. Receives: Drug: B/F/TAF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic failure - 200 Copies/mL cut-off
Proportion of participants with HIV-1 RNA at least 200 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
Measured: Week 48
Secondary outcomes (11)
Virologic failure - 50 Copies/mL cut-off
Proportion of participants with HIV-1 RNA at least 50 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
Measured: Week 48
Virologic failure - 1000 Copies/mL cut-off
Proportion of participants with HIV-1 RNA at least 1000 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
Measured: Week 48
Tolerability as measured by discontinuing medication
Proportion of participants discontinuing therapy for drug-related adverse events
Measured: Entry to 48 weeks
Adverse events
Proportion of participants with 1 or more NIH Division of AIDS Grade 3 or 4 adverse events (at least 1 grade increase from baseline)
Measured: Entry to 48 weeks
Change in cholesterol
Median change in cholesterol
Measured: Entry to 48 weeks
Change in weight
Median change in weight in kilograms
Measured: Entry to 48 weeks
Change in body mass index
Median change in body mass index (weight in kilograms divided by the square of height in meters)
Measured: Entry to 48 weeks
Weight gain of 10% or greater
Proportion of participants with weight gain of at least 10% (in kilograms)
Measured: Entry to 48 weeks
Change in waist circumference
Median change in waist circumference
Measured: Entry to 48 weeks
Waist to hip ratio
Median change in waist to hip ratio
Measured: Entry to 48 weeks
Adherence
Median adherence as measured by pharmacy refill records
Measured: Entry to 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2020
- Study start1 Sep 2020 (estimated)
- Primary completion31 May 2022 (estimated)
- Study completion30 Nov 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV-1-infectionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized to the B/F/TAF or continuation bPI group in a 1:1 ratio.
- Masking
- None (open label)
- Enrolment
- 386 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Harvard Medical School (HMS and HSDM), Analysis Group, Inc., Weill Medical College of Cornell University
- Responsible party
- Sponsor
- Investigators
- Patrice Severe, MD, Principal investigator, Haitian Group for the Study of Kaposi's Sarcoma and OpportunisticSerena Koenig, MD, Principal investigator, Brigham and Women's Hospital/Harvard Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04311957
- Sponsor's protocol ID
- CO-US-380-5733
- Status last verified
- Jul 2020
- First submitted
- 15 Mar 2020
- Last updated
- 3 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Severe P, Pierre S, Homeus F, Marc JB, Trevisi L, Aristhomene ML, Bernadin GR, Lavoile K, Rivera V, Duchatellier CF, Joseph MJ, Wu J, Rouzier V, Preval F, Jean E, Bernadin J, Zion A, Pierre Louis Forestal G, Avila-Rios S, Garcia Morales C, Zhang A, Israelski D, Apollon A, Dumont E, Fox E, Cremieux PY, Pape JW, Collins SE, Liautaud B, Sax PE, Koenig SP. Bictegravir, emtricitabine, and tenofovir alafenamide versus ritonavir-boosted protease inhibitor-based antiretroviral therapy in people with HIV and viral suppression on second-line therapy in Haiti: an open-label, randomised, non-inferiority trial. Lancet HIV. 2025 Sep;12(9):e616-e626. doi: 10.1016/S2352-3018(25)00130-4.
PubMed 40883049
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Non-Inferiority Trial to Compare the Efficacy of Switching From Protease-Inhibitor Based Second-Line Therapy to Bictegravir-Tenofovir Alafenamide-Emtricitabine in Virologically Suppressed Adults in Haiti
- ClinicalTrials.gov ID
- NCT04311957
- Acronym / sponsor ID
- CO-US-380-5733
- Conditions
- HIV-1-infection, Antiretroviral Therapy
- Keywords
- HIV, Second-line therapy, Integrase strand transfer inhibitor, Protease inhibitor
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 386 participants (estimated)
- Lead sponsor
- Haitian Group for the Study of Kaposi's Sarcoma and OpportunisticUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Harvard Medical School (HMS and HSDM), Analysis Group, Inc., Weill Medical College of Cornell University
- Study start
- 1 Sep 2020 (estimated)
- Primary completion
- 31 May 2022 (estimated)
- Study completion
- 30 Nov 2022 (estimated)
- First posted
- 17 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized trial compares the efficacy of switching to a fixed-dose combination of B/F/TAF versus continuing a boosted protease inhibitor (bPI) regimen in HIV-1 infected participants who are virologically suppressed (HIV-1 RNA <200 copies) on a second-line bPI regimen. Half of participants will receive B/F/TAF and half will continue a bPI regimen. The hypothesize is that B/F/TAF will have efficacy that is non-inferior to the boosted PI regimen.
Detailed description
The second generation integrase strand transfer inhibitors (INSTIs) dolutegravir (DTG) and bictegravir (BIC) are widely prescribed for the treatment of HIV, due to their favorable tolerability and toxicity profile, durable efficacy, and high barrier to resistance. However, there are limited data to guide the management of patients who are already virally suppressed on a second-line bPI regimen.
Though bPIs have a high barrier to resistance and durable virologic efficacy, they have several important drug-drug interactions, are associated with unfavorable long-term metabolic effects, and may be poorly tolerated. For these reasons, a second-generation INSTI would be preferable to a boosted PI regimen, as long INSTIs are demonstrated to have non-inferior efficacy for patients who are already suppressed on a second-line bPI regimen.
In the proposed study, the efficacy of continuing the bPI regimen will be compared to switching to B/F/TAF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will be randomized to the B/F/TAF or continuation bPI group in a 1:1 ratio.
| Arm | Type | Receives |
|---|---|---|
| Boosted PI Group | Active comparator | Drug: Continuation of boosted PIContinuation of the same second-line regimen taken prior to entry: This includes either Lopinavir/ritonavir (LPVr) 400 mg/100 mg BID or Atazanavir/ritonavir (ATV/r) 300 mg/100 mg QD plus 2 nucleoside reverse transcriptase inhibitors (NRTIs). |
| B/F/TAF Group | Experimental | Drug: B/F/TAFCombination tablet of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The ability and willingness to give informed consent.
- Age ≥18 years
- History of meeting WHO criteria for immunologic or virologic failure after receipt of a first-line treatment regimen for ≥6 months
- Currently receiving a second-line ART regimen including either ATVr or LPVr + 2 NRTIs for ≥6 months
- At least one HIV-1 RNA <200 copies/mL within 12 months prior to enrollment, and no HIV-1 RNA of at least 200 copies/mL during this period.
Key exclusion criteria (7 listed)
- Active World Health Organization Stage 3 or 4 condition
- Treatment with an INSTI in the past
- Gap in care of at least one month in the prior six months
- Current alcohol or substance use judged by investigator to potentially interfere with participant study compliance
- History of poor adherence, that in the opinion of the investigator, would potentially interfere with study compliance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Continuation of boosted PIContinuation of the same second-line regimen taken prior to entry: LPVr 400 mg/100 mg BID or ATVr 300 mg/100 mg QD + 2 NRTIs | Drug | Boosted PI Group |
| B/F/TAFSingle-tablet, fixed dose combination of bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg (B/F/TAF) administered orally, once daily. | Drug | B/F/TAF Group |
Primary outcome
Virologic failure - 200 Copies/mL cut-off
Time frame: Week 48
Proportion of participants with HIV-1 RNA at least 200 copies/mL at Week 48 as defined by the US FDA-defined snapshot algorithm
11 secondary outcomes
Virologic failure - 50 Copies/mL cut-off
Time frame: Week 48
Virologic failure - 1000 Copies/mL cut-off
Time frame: Week 48
Tolerability as measured by discontinuing medication
Time frame: Entry to 48 weeks
Adverse events
Time frame: Entry to 48 weeks
Change in cholesterol
Time frame: Entry to 48 weeks
Change in weight
Time frame: Entry to 48 weeks
Change in body mass index
Time frame: Entry to 48 weeks
Weight gain of 10% or greater
Time frame: Entry to 48 weeks
Change in waist circumference
Time frame: Entry to 48 weeks
Waist to hip ratio
Time frame: Entry to 48 weeks
Adherence
Time frame: Entry to 48 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2020.
- Derived from this study: PubMed 40883049Severe P, Pierre S, Homeus F, Marc JB, Trevisi L, Aristhomene ML, Bernadin GR, Lavoile K, Rivera V, Duchatellier CF, Joseph MJ, Wu J, Rouzier V, Preval F, Jean E, Bernadin J, Zion A, Pierre Louis Forestal G, Avila-Rios S, Garcia Morales C, Zhang A, Israelski D, Apollon A, Dumont E, Fox E, Cremieux PY, Pape JW, Collins SE, Liautaud B, Sax PE, Koenig SP. Bictegravir, emtricitabine, and tenofovir alafenamide versus ritonavir-boosted protease inhibitor-based antiretroviral therapy in people with HIV and viral suppression on second-line therapy in Haiti: an open-label, randomised, non-inferiority trial. Lancet HIV. 2025 Sep;12(9):e616-e626. doi: 10.1016/S2352-3018(25)00130-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrice Severe, MD principal investigator
Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic
Serena Koenig, MD principal investigator
Brigham and Women's Hospital/Harvard Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Continuation of boosted PI and B/F/TAF in people with HIV-1-infection and Antiretroviral Therapy, run by Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic at 1 site in Haiti.
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 7 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: status not confirmed, as of the sponsor's last update on 3 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Haiti. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Patrice Severe, MD (718-962-4585, patsevere@gheskio.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virologic failure - 200 Copies/mL cut-off (time frame: Week 48). 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 NCT04311957, which also lists 1 linked publication.
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 3 Aug 2020.