Acquired Immunodeficiency SyndromePhase 4NCT05493969
Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity
A Phase 4 study testing Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG) in people with Acquired Immunodeficiency Syndrome, run by Shanghai Public Health Clinical Center.
Trial summary
To investigate the efficacy and tolerability of the regimen of dolutegravir plus lamivudine in HIV infected adults who are virologically suppressed and with evidence of TDF toxicity. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Acquired Immunodeficiency Syndrome
- What is being tested?
- Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Aug 2022to Jun 2026
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female subjects were required to meet one of the following criteria: 1) Incapacitated, defined as postmenopausal (spontaneous amenorrhea at 12 months, age ≥45 years) or physically unable to conceive after tubal ligation, hysterectomy, or bilateral oophorectomy; 2) Have potential to have children, but are negative at screening and on day 1 pregnancy test, and agree to use appropriate contraceptive methods, including oral contraceptives, condoms and intrauterine devices;
- At least once plasma HIV-1 RNA<40 c/mL in the 6 months prior to screening and plasma HIV-1 RNA <40 c/mL at screening;
- Must be on uninterrupted TDF + 3TC/FTC-based regimen for ≥6 months prior to screening;
- Participants with pre-existing clinical manifestations of TDF related adverse reactions at the time of screening.
- TDF-related renal damage was defined as: meeting 1 of the 5 following conditions in the investigator's judgement, based upon the medical history and relevant examinations, likely to represent TDF toxicity:
- eGFR decrease by 5 mL/min per year for at least 3 consecutive years or confirmed 25% eGFR decline from baseline ii. Urine β2-microglobulin/Cr ≥300 μg/g iii. Urine microalbumin/creatinine >30 μg/mg iv. Non-diabetic glycosuria (urine glucose 1+ or above) v. Serum phosphate <0.8 mmol/L TDF - associated bone toxicity is defined as a T-value less than -1.0 or Z- value less than -2.0 or fragility fracture after TDF/XTC use and other factors is excluded according to the medical history and relevant examination.
- Sign the informed consent and be able to visit regularly according to the test requirements.
Who cannot join
- Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study;
- Participants with AIDS-related opportunistic infections or AIDS-related or unrelated neoplastic diseases;
- Patients with ALT >= 5 x ULN, or ALT >=3 x ULN and bilirubin >= 1.5xULN (with >35% direct bilirubin. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Evidence of Hepatitis B virus (HBV) infection: Participants positive for HBsAg, negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
- Hepatitis C virus (HCV) infection;
- Participants who are allergic or intolerant to lamivudine or dolutegravir;
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- Participants with known previous episodes of virologic failure and known resistance mutations of 3TC or INSTI if resistance mutations had previously been identified;
- Taking medications that contraindicated with lamivudine or dolutegravir; Other conditions that the investigator considers unsuitable to participate in the study, including the risk of suicide, poor adherence, and interference with the evaluation of clinical study endpoints.
- Participants with creatinine clearance <30ml/min.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: A Study Evaluating the Efficacy and Tolerability of Dolutegravir Plus Lamivudine in HIV Infected Adults Who Are Virologically Suppressed and With Evidence of TDF Toxicity
To investigate the efficacy and tolerability of the regimen of dolutegravir plus lamivudine in HIV infected adults who are virologically suppressed and with evidence of TDF toxicity.
Read the detailed description
This study is a single-center, prospective, uncontrolled, open-label and single-arm interventional study, and aim to investigate the efficacy and safety of dolutegravir plus lamivudine (DTG+3TC) for HIV-infected adults switching from TDF-based triple ART due to TDF toxicity. The study populations are : HIV-infected patients, irrespective of gender, aged 18-75 years old; At least one plasma HIV-1 RNA<40 c/mL in the 6 months prior to Screening and plasma HIV-1 RNA <40 c/mL at Screening; Must be on uninterrupted TDF + 3TC / FTC-based regimen for ≥ 6 months prior to Screening; There are clinical manifestations of TDF related adverse reactions. All enrolled subjects will receive DTG + 3TC once daily (DTG + 3TC) for up to 48 weeks. After stable switch indication approved in China mainland, it's allowed for subjects switch from DTG+3TC to fixed dose combination DTG/3TC. The primary endpoint is the percentage of participants with virologic failure at 48 weeks of treatment by FDA Snapshot algorithm. The secondary endpoints are immunologic outcomes and adverse events including bone and renal biomarkers.
- Conditions
- Acquired Immunodeficiency Syndrome
- Being tested
- Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)Drug
Subjects will discontinue their TDF + 3TC/FTC-based regimen and will switch to DTG+3TC or fixed dose combination DTG/3TC.
| Study group | Role | What they receive |
|---|---|---|
| DTG/3TC | Other | Subjects will switch to dolutegravir (DTG) plus lamivudine (3TC) or fixed dose combination DTG/3TC for 48 weeks. Receives: Drug: Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Virologic outcomes
Percentage of participants with virologic failure after 48 weeks of treatment by FDA Snapshot algorithm.
Measured: Week 48
Secondary outcomes (6)
HIV-RNA
Percentage of participants with HIV-RNA <40 copies/mL at weeks 24 and 48
Measured: Week 24 and Week 48
CD4 counts
Changes from Baseline in CD4+ Cell Counts at Week 24 and 48
Measured: Week 24 and Week 48
bone markers
Median percentage improvement (±SD) of circulating bone markers (alkaline phosphatase, osteocalcin, 25-OH-vitamin D level) at 24 weeks and 48 weeks after switch vs baseline)
Measured: Week 48
DEXA
Percentage change of T-score classification (normal, osteopenia and osteoporosis) or Z-score classification (normal, abnormal) of bone mineral density using DEXA at 48 weeks after switch vs baseline
Measured: Week 48
renal markers
Median percentage improvement (±SD) of urine microalbumin , serum CysC, urine β2-microglobulin/creatinine, urine N-Acetyl-Beta-D-Glucosaminidase (NAG), serum retinol binding protein (RBP) at 24 weeks and 48 weeks after switch vs baseline
Measured: Week 24 and Week 48
eGFR
Median percentage improvement (±SD) of eGFR and Percentage change of renal function (normal, mild, moderate and severe) at 24 weeks and 48 weeks after switch vs baseline
Measured: Week 24 and Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Aug 2022
- Study startAug 2022 (estimated)
- Primary completionAug 2025 (estimated)
- Study completionJun 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 Acquired Immunodeficiency SyndromeStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Public Health Clinical Center
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Renfang Zhang, Shanghai Public Health Clinical Center
- Investigators
- Renfang Zhang, Study chair, Shanghai Public Health Clinical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05493969
- Sponsor's protocol ID
- 2432
- Status last verified
- Aug 2022
- First submitted
- 5 Aug 2022
- Last updated
- 9 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wang Z, Liu L, Chen J, Wang J, Shen Y, Qi T, Tang Y, Song W, Sun J, Xu S, Yang J, Chen Y, Shao Y, Zhang R. Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed HIV-1 Infected Adults with TDF-Related Renal or Bone Toxicity. Infect Dis Ther. 2026 Jul;15(7):1913-1924. doi: 10.1007/s40121-026-01363-y. Epub 2026 May 20.
PubMed 42162408
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study Evaluating the Efficacy and Tolerability of Dolutegravir Plus Lamivudine in HIV Infected Adults Who Are Virologically Suppressed and With Evidence of TDF Toxicity
- ClinicalTrials.gov ID
- NCT05493969
- Acronym / sponsor ID
- 2432
- Conditions
- Acquired Immunodeficiency Syndrome
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Shanghai Public Health Clinical CenterOther government
- Study start
- Aug 2022 (estimated)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 9 Aug 2022 (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.
To investigate the efficacy and tolerability of the regimen of dolutegravir plus lamivudine in HIV infected adults who are virologically suppressed and with evidence of TDF toxicity.
Detailed description
This study is a single-center, prospective, uncontrolled, open-label and single-arm interventional study, and aim to investigate the efficacy and safety of dolutegravir plus lamivudine (DTG+3TC) for HIV-infected adults switching from TDF-based triple ART due to TDF toxicity. The study populations are : HIV-infected patients, irrespective of gender, aged 18-75 years old; At least one plasma HIV-1 RNA<40 c/mL in the 6 months prior to Screening and plasma HIV-1 RNA <40 c/mL at Screening; Must be on uninterrupted TDF + 3TC / FTC-based regimen for ≥ 6 months prior to Screening; There are clinical manifestations of TDF related adverse reactions. All enrolled subjects will receive DTG + 3TC once daily (DTG + 3TC) for up to 48 weeks. After stable switch indication approved in China mainland, it's allowed for subjects switch from DTG+3TC to fixed dose combination DTG/3TC. The primary endpoint is the percentage of participants with virologic failure at 48 weeks of treatment by FDA Snapshot algorithm. The secondary endpoints are immunologic outcomes and adverse events including bone and renal biomarkers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DTG/3TC | Other | Drug: Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)Subjects will switch to dolutegravir (DTG) plus lamivudine (3TC) or fixed dose combination DTG/3TC for 48 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Female subjects were required to meet one of the following criteria: 1) Incapacitated, defined as postmenopausal (spontaneous amenorrhea at 12 months, age ≥45 years) or physically unable to conceive after tubal ligation, hysterectomy, or bilateral oophorectomy; 2) Have potential to have children, but are negative at screening and on day 1 pregnancy test, and agree to use appropriate contraceptive methods, including oral contraceptives, condoms and intrauterine devices;
- At least once plasma HIV-1 RNA<40 c/mL in the 6 months prior to screening and plasma HIV-1 RNA <40 c/mL at screening;
- Must be on uninterrupted TDF + 3TC/FTC-based regimen for ≥6 months prior to screening;
- Participants with pre-existing clinical manifestations of TDF related adverse reactions at the time of screening.
- TDF-related renal damage was defined as: meeting 1 of the 5 following conditions in the investigator's judgement, based upon the medical history and relevant examinations, likely to represent TDF toxicity:
Key exclusion criteria (9 listed)
- Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study;
- Participants with AIDS-related opportunistic infections or AIDS-related or unrelated neoplastic diseases;
- Patients with ALT >= 5 x ULN, or ALT >=3 x ULN and bilirubin >= 1.5xULN (with >35% direct bilirubin. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Evidence of Hepatitis B virus (HBV) infection: Participants positive for HBsAg, negative for anti-HBs but positive for anti-HBc (negative HBsAg status) and positive for HBV DNA are excluded.
- Hepatitis C virus (HCV) infection;
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 |
|---|---|---|
| Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)Subjects will discontinue their TDF + 3TC/FTC-based regimen and will switch to DTG+3TC or fixed dose combination DTG/3TC. | Drug | DTG/3TC |
Primary outcome
Virologic outcomes
Time frame: Week 48
Percentage of participants with virologic failure after 48 weeks of treatment by FDA Snapshot algorithm.
6 secondary outcomes
HIV-RNA
Time frame: Week 24 and Week 48
CD4 counts
Time frame: Week 24 and Week 48
bone markers
Time frame: Week 48
DEXA
Time frame: Week 48
renal markers
Time frame: Week 24 and Week 48
eGFR
Time frame: Week 24 and Week 48
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2022.
- Derived from this study: PubMed 42162408Wang Z, Liu L, Chen J, Wang J, Shen Y, Qi T, Tang Y, Song W, Sun J, Xu S, Yang J, Chen Y, Shao Y, Zhang R. Efficacy and Safety of Switching to Dolutegravir/Lamivudine in Virologically Suppressed HIV-1 Infected Adults with TDF-Related Renal or Bone Toxicity. Infect Dis Ther. 2026 Jul;15(7):1913-1924. doi: 10.1007/s40121-026-01363-y. Epub 2026 May 20.
- Individual participant dataSharing planned: No
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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.
Renfang Zhang study chair
Shanghai Public Health Clinical Center
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG) in people with Acquired Immunodeficiency Syndrome, run by Shanghai Public Health Clinical Center.
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 7 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: status not confirmed, as of the sponsor's last update on 9 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
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 Renfang Zhang (+86-18916051096, zhangrenfang@shaphc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Virologic outcomes (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 NCT05493969, 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 9 Aug 2022.