Efficacy and Tolerability of DTG Plus 3TC in HIV Infected Adults With Virologically Suppression and TDF Toxicity

NCT05493969 | Not Yet Recruiting Phase 4

• 1 other identifier: 2432
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Acquired Immunodeficiency Syndrome

Outcome Measures

Primary Outcomes (1)

• Virologic outcomes

  Percentage of participants with virologic failure after 48 weeks of treatment by FDA Snapshot algorithm.

  Week 48

Secondary Outcomes (6)

• HIV-RNA

  Week 24 and Week 48

• CD4 counts

  Week 24 and Week 48

• bone markers

  Week 48

• DEXA

  Week 48

• renal markers

  Week 24 and Week 48

Study Arms (1)

DTG/3TC

OTHER

Subjects will switch to dolutegravir (DTG) plus lamivudine (3TC) or fixed dose combination DTG/3TC for 48 weeks.

Drug: Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)

Interventions

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.

DTG/3TC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• i. 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.

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Shanghai Public Health Clinical Center: lead

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

dolutegravir; Lamivudine

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Study Officials

• Renfang Zhang

  Shanghai Public Health Clinical Center

  STUDY CHAIR

Central Study Contacts

Renfang Zhang

CONTACT

+86-18916051096; zhangrenfang@shaphc.org

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical professor

Study Record Dates

• First Submitted: August 5, 2022
• First Posted: August 9, 2022
• Study Start: August 1, 2022
• Primary Completion: August 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: August 9, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share