HIV-1-infectionPhase 3Opti-DORNCT05924438
A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy
A Phase 3 study testing Delstrigo and KOCITAF in people with HIV-1-infection, run by Professor Francois Venter at 1 site in South Africa.
Trial summary
This is an open label, randomised, phase 3, two-arm study conducted over 96 weeks. The study includes a screening period day - 60 to -1, enrolment visit day 0, and a 96-week treatment follow-up period. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- HIV-1-infection
- What is being tested?
- Delstrigo and KOCITAF
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 600 participants
- Where
- 1 siteSouth Africa
- Study dates
- 8 Nov 2023to 30 Jun 2026
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Each participant must meet all the following criteria to be enrolled in this study.
- ≥18 years old, male or female.
- Documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening, with no baseline DOR resistance (please see Table 2 below).
- Is ART naïve.
- BMI≥ 25 kg/cm2.
- VL >500 copies/ml.
- Must sign an ICF indicating that he or she understands the purpose of, and procedures required for the study and is willing to participate in the study.
- Female participants of childbearing potential (WOCBP) are eligible to participate if willing to use highly effective contraception methods from enrolment, for the duration of the study.
Who cannot join
- Participants meeting any of the following criteria will be excluded from the study:
- Is currently participating in any other interventional study or participated in a study with an investigational drug within 60 days of screening.
- Is pregnant, breastfeeding or intends to become pregnant or breastfeed during the study.
- Has active TB co-infection and requires anti-TB treatment.
- Has unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); Child-Pugh C.
- Has pre-existing physical or mental condition (including substance abuse disorder and suicide risk) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
Show all 9Show fewer
- Clinically unstable in the investigator's opinion (any pre-existing medical or laboratory abnormalities must be deemed to be stable by the investigator prior to study enrolment).
- Has estimated creatinine clearance <60mL/min per Cockcroft-Gault formula.
- Is taking, and is unable to discontinue, any of the following prohibited medications: carbamazepine, oxcarbazepine, phenobarbital, phenytoin; the antimycobacterial rifampicin, rifapentine; St. John's Wort (Hypericum perforatum); mitotane; enzalutamide; lumacaftor.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Opti-DOR: A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy
This is an open label, randomised, phase 3, two-arm study conducted over 96 weeks.
The study includes a screening period day - 60 to -1, enrolment visit day 0, and a 96-week treatment follow-up period.
Approximately 600 male and female participants infected with HIV-1 eligible for first-line therapy, will be randomly assigned in a 1:1 ratio approximately 300 participants per treatment group to either Treatment Group 1 DOR/3TC/TDF or Treatment Group 2 DTG/TAF/FTC. All medications will be administered in an open label design.
Read the detailed description
One of the major concerns, voiced by researchers, clinicians, and participants, is that data is severely limited to inform participants with side effects, or those wanting to avoid these side effects, as to evidence-based alternatives. As a result, there are no evidence-based regimens available for participants who have begun experiencing weight gain as a side effect on treatment or wanting to avoid weight gain on initiation of antiretrovirals which is now an almost routine side effect for women or Black participants.
Switching to efavirenz-based regimens, while plausibly associated with weight mitigation in efavirenz slow-metabolizers, is accompanied by unacceptable metabolic, organ and neuropsychiatric side effects in the slow metabolizers likely to experience weight loss. There is minimal data on weight changes for switches from integrase inhibitors and having evidence-based options would dramatically add to treatment possibilities for participants. There is some evidence that the use of TDF and doravirine may mitigate the weight gain seen with TAF/integrase inhibitors combinations.
Doravirine is a compelling replacement for the integrase inhibitors similarly well tolerated, and with a high resistance barrier and better lipid profile as compared to other drugs in the non-nucleoside reverse-transcriptase inhibitor class14. In a recent network meta-analysis, DOR/3TC/TDF was found to exhibit superiority in virological suppression to traditional first line non-DTG containing regimes with more tolerable side effects, and a decrease in severe adverse events.
The DOR/3TC/TDF combination would be a major step forward for current treatment guidelines if found to be equivalent in terms of virological suppression and showed a meaningful difference in weight gain, as well as in cardiometabolic outcomes. This potentially offers clinicians and high risk participants an evidence-based alternative to TAF/integrase inhibitor combinations.
We propose a head-to-head, non-inferiority, randomized study with DTG/TAF/FTC, against a formulation of DOR/3TC/TDF, in antiretroviral-naïve overweight participants, with differences in viral suppression as the primary end points weight gain and metabolic changes-being secondary endpoints of interest at 48 Weeks.
- Conditions
- HIV-1-infection
- Being tested
- Delstrigo, KOCITAF
- Keywords
- delstrigo, KOCITAF, doravirine, HIV-1 RNA, dolutegravir, weight gain
- Medical subject headings
- Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DelstrigoDrug
Treatment Group 1 Participants will receive Doravirine, as part of a fixed-dose oral combination with lamivudine and tenofovir disoproxil fumarate (DOR/3TC/TDF, Delstrigo)tablets which are to be administered orally and once daily.
KOCITAFDrug
Treatment Group 2 Participants will receive dolutegravir, as part of a fixed-dose oral combination with tenofovir alafenamide plus emtricitabine (DTG/TAF/FTC, KOCITAF) tablets which are to be administered orally and once daily.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group 1 | Experimental | Delstrigo Receives: Drug: Delstrigo |
| Treatment Group 2 | Other | KOCITAF Receives: Drug: KOCITAF |
What is being measured
The primary outcome is the main question the study is designed to answer.
The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC in the first line treatment, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48
HIV1-RNA
Measured: 48 Weeks
Secondary outcomes (11)
The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96
HIV-1 RNA
Measured: 96 Weeks
The antiretroviral activity of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 and Week 96
HIV-1 RNA
Measured: 48 and 96 Weeks
Time to virologic failure (defined as confirmed HIV-1 RNA levels ≥ 1000 copies/mL at week 24 or ≥ 200 copies/mL after week 24)
HIV-1 RNA
Measured: 24 Weeks
The immunologic effect of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline in CD4+ T-cell count at Week 48 and Week 96
CD4-T-cell count
Measured: 48 and 96 Weeks
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Adverse events
Measured: 96 Weeks
The effect of DOR/3TC/TDF compared with DTG/TAF/FTC on weight, as assessed by the mean change from baseline to Week 48 and Week 96
Weight
Measured: 48 and 96 Weeks
The effect on body composition of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96.
Dual-energy X-ray absorptiometry (DXA) scan
Measured: 48 and 96 Weeks
The effect on hematology of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96.
Full blood count
Measured: 48 and 96 Weeks
The effect on lipid profile of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96
fasting lipogram
Measured: 48 and 96 Weeks
To evaluate the pharmacokinetics of DOR in pregnant women
Peak Plasma Concentration (Cmax)
Measured: 96 Weeks
To evaluate the pharmacokinetics of DOR in pregnant women
Area under the plasma concentration versus time curve (AUC)
Measured: 96 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jun 2023
- Study start8 Nov 2023
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 600 participants (actual)
Sponsor and investigators
- Lead sponsor
- Professor Francois Venter
- Sponsor type
- University, hospital or other
- Collaborators
- Africa Health Research Institute, Merck Sharp & Dohme LLC
- Responsible party
- Sponsor-investigator, Professor Francois Venter, University of Witwatersrand, South Africa
- Investigators
- JOANA FRANCISCA WOODS, MBBCh, Principal investigator, Ezintsha Resesarch CentreSIMISO MANDISA Sokhela, MBBCh, Study director, Ezintsha Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05924438
- Sponsor's protocol ID
- EZ-JW-033
- Other IDs
- DOH-27-052023-5232
- Acronym
- Opti-DOR
- Status last verified
- Mar 2025
- First submitted
- 23 May 2023
- Last updated
- 2 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Woods J, Lebina L, Moller K, Venter WDF, Akpomiemie G, Manentsa N, Taukobong I, Macholo P, Behuhuma NO, Lalla-Edward ST, Manne-Goehler J, Siedner MJ, Collings T, Mashabane N, Hill A, Sokhela SM. Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: The Opti-DOR Randomized Clinical Trial. JAMA. 2026 Jul 31:e2614762. doi: 10.1001/jama.2026.14762. Online ahead of print.
PubMed 42536019
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Opti-DOR: A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy
- ClinicalTrials.gov ID
- NCT05924438
- Acronym / sponsor ID
- Opti-DOR / EZ-JW-033
- Conditions
- HIV-1-infection
- Keywords
- delstrigo, KOCITAF, doravirine, HIV-1 RNA, dolutegravir, weight gain
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 600 participants (actual)
- Lead sponsor
- Professor Francois VenterUniversity, hospital or other
- Collaborators
- Africa Health Research Institute, Merck Sharp & Dohme LLC
- Study start
- 8 Nov 2023 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 29 Jun 2023 (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 is an open label, randomised, phase 3, two-arm study conducted over 96 weeks.
The study includes a screening period day - 60 to -1, enrolment visit day 0, and a 96-week treatment follow-up period.
Approximately 600 male and female participants infected with HIV-1 eligible for first-line therapy, will be randomly assigned in a 1:1 ratio approximately 300 participants per treatment group to either Treatment Group 1 DOR/3TC/TDF or Treatment Group 2 DTG/TAF/FTC. All medications will be administered in an open label design.
Detailed description
One of the major concerns, voiced by researchers, clinicians, and participants, is that data is severely limited to inform participants with side effects, or those wanting to avoid these side effects, as to evidence-based alternatives. As a result, there are no evidence-based regimens available for participants who have begun experiencing weight gain as a side effect on treatment or wanting to avoid weight gain on initiation of antiretrovirals which is now an almost routine side effect for women or Black participants.
Switching to efavirenz-based regimens, while plausibly associated with weight mitigation in efavirenz slow-metabolizers, is accompanied by unacceptable metabolic, organ and neuropsychiatric side effects in the slow metabolizers likely to experience weight loss. There is minimal data on weight changes for switches from integrase inhibitors and having evidence-based options would dramatically add to treatment possibilities for participants. There is some evidence that the use of TDF and doravirine may mitigate the weight gain seen with TAF/integrase inhibitors combinations.
Doravirine is a compelling replacement for the integrase inhibitors similarly well tolerated, and with a high resistance barrier and better lipid profile as compared to other drugs in the non-nucleoside reverse-transcriptase inhibitor class14. In a recent network meta-analysis, DOR/3TC/TDF was found to exhibit superiority in virological suppression to traditional first line non-DTG containing regimes with more tolerable side effects, and a decrease in severe adverse events.
The DOR/3TC/TDF combination would be a major step forward for current treatment guidelines if found to be equivalent in terms of virological suppression and showed a meaningful difference in weight gain, as well as in cardiometabolic outcomes. This potentially offers clinicians and high risk participants an evidence-based alternative to TAF/integrase inhibitor combinations.
We propose a head-to-head, non-inferiority, randomized study with DTG/TAF/FTC, against a formulation of DOR/3TC/TDF, in antiretroviral-naïve overweight participants, with differences in viral suppression as the primary end points weight gain and metabolic changes-being secondary endpoints of interest at 48 Weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment Group 1 | Experimental | Drug: DelstrigoDelstrigo |
| Treatment Group 2 | Other | Drug: KOCITAFKOCITAF |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Each participant must meet all the following criteria to be enrolled in this study.
- ≥18 years old, male or female.
- Documented laboratory diagnosis of infection with HIV-1 (positive enzyme-linked immunosorbent assay HIV-1 antibody test) at screening, with no baseline DOR resistance (please see Table 2 below).
- Is ART naïve.
- BMI≥ 25 kg/cm2.
Key exclusion criteria (9 listed)
- Is currently participating in any other interventional study or participated in a study with an investigational drug within 60 days of screening.
- Is pregnant, breastfeeding or intends to become pregnant or breastfeed during the study.
- Has active TB co-infection and requires anti-TB treatment.
- Has unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones); Child-Pugh C.
- Has pre-existing physical or mental condition (including substance abuse disorder and suicide risk) which, in the opinion of the Investigator, may interfere with the participant's ability to comply with the dosing schedule and/or protocol evaluations or which may compromise the safety of the participant.
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 |
|---|---|---|
| DelstrigoTreatment Group 1 Participants will receive Doravirine, as part of a fixed-dose oral combination with lamivudine and tenofovir disoproxil fumarate (DOR/3TC/TDF, Delstrigo)tablets which are to be administered orally and once daily. | Drug | Treatment Group 1 |
| KOCITAFTreatment Group 2 Participants will receive dolutegravir, as part of a fixed-dose oral combination with tenofovir alafenamide plus emtricitabine (DTG/TAF/FTC, KOCITAF) tablets which are to be administered orally and once daily. | Drug | Treatment Group 2 |
Primary outcome
The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC in the first line treatment, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48
Time frame: 48 Weeks
HIV1-RNA
11 secondary outcomes
The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96
Time frame: 96 Weeks
The antiretroviral activity of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 and Week 96
Time frame: 48 and 96 Weeks
Time to virologic failure (defined as confirmed HIV-1 RNA levels ≥ 1000 copies/mL at week 24 or ≥ 200 copies/mL after week 24)
Time frame: 24 Weeks
The immunologic effect of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline in CD4+ T-cell count at Week 48 and Week 96
Time frame: 48 and 96 Weeks
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Time frame: 96 Weeks
The effect of DOR/3TC/TDF compared with DTG/TAF/FTC on weight, as assessed by the mean change from baseline to Week 48 and Week 96
Time frame: 48 and 96 Weeks
The effect on body composition of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96.
Time frame: 48 and 96 Weeks
The effect on hematology of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96.
Time frame: 48 and 96 Weeks
The effect on lipid profile of DOR/3TC/TDF compared with DTG/TAF/FTC, as assessed by the mean change from baseline to Week 48 and Week 96
Time frame: 48 and 96 Weeks
To evaluate the pharmacokinetics of DOR in pregnant women
Time frame: 96 Weeks
To evaluate the pharmacokinetics of DOR in pregnant women
Time frame: 96 Weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2025.
- Derived from this study: PubMed 42536019Woods J, Lebina L, Moller K, Venter WDF, Akpomiemie G, Manentsa N, Taukobong I, Macholo P, Behuhuma NO, Lalla-Edward ST, Manne-Goehler J, Siedner MJ, Collings T, Mashabane N, Hill A, Sokhela SM. Initial HIV Therapy for Adults and Treatment-Associated Weight Gain: The Opti-DOR Randomized Clinical Trial. JAMA. 2026 Jul 31:e2614762. doi: 10.1001/jama.2026.14762. Online ahead of print.
- Individual participant dataSharing planned: Yes
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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.
JOANA FRANCISCA WOODS, MBBCh principal investigator
Ezintsha Resesarch Centre
SIMISO MANDISA Sokhela, MBBCh study director
Ezintsha Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Delstrigo and KOCITAF in people with HIV-1-infection, run by Professor Francois Venter at 1 site 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 8 inclusion and 9 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: under way, not looking for participants, as of the sponsor's last update on 2 Apr 2025. 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 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?
This study is still under way. Results are not available in the source record yet.
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?
The antiretroviral activity of DOR/3TC/TDF compared to DTG/TAF/FTC in the first line treatment, as assessed by the percentage of participants with HIV-1 RNA < 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 NCT05924438, 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 2 Apr 2025.