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

Launched by SHANGHAI PUBLIC HEALTH CLINICAL CENTER · Aug 6, 2022

Keywords

ClinConnect Summary

This clinical trial is looking at how effective and tolerable a combination of two medications, dolutegravir (DTG) and lamivudine (3TC), is for adults living with HIV who have stable viral suppression but are experiencing side effects from another medication called TDF. The goal is to see if switching to this new regimen can help these patients without causing additional problems.

To be eligible for the study, participants should be adults aged 18 and older who have been taking TDF and 3TC for at least six months and have shown stable HIV levels (with no detectable virus) during that time. They should also have signs of TDF-related side effects, like kidney or bone issues. Women who can get pregnant need to agree to use birth control during the study. The trial is not yet recruiting participants, but if you qualify, you can expect regular visits for monitoring and support throughout the trial. This study is important as it may offer a safer treatment option for those affected by TDF toxicity.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. 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;
• • 2. 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;
• • 3. Must be on uninterrupted TDF + 3TC/FTC-based regimen for ≥6 months prior to screening;
• • 4. 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.
• • 5. Sign the informed consent and be able to visit regularly according to the test requirements.
• Exclusion Criteria:
• • 1. Women who are pregnant or breastfeeding or plan to become pregnant or breastfeed during the study;
• • 2. Participants with AIDS-related opportunistic infections or AIDS-related or unrelated neoplastic diseases;
• • 3. 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).
• • 4. 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.
• • 5. Hepatitis C virus (HCV) infection;
• • 6. Participants who are allergic or intolerant to lamivudine or dolutegravir;
• • 7. Participants with known previous episodes of virologic failure and known resistance mutations of 3TC or INSTI if resistance mutations had previously been identified;
• • 8. 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.
• • 9. Participants with creatinine clearance \<30ml/min.