HIV infection MedDRA version: 20.1 Level: LLT Classification code 10008919 Term: Chronic HIV infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Tivicay
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Dolutegravir
Other descriptive name: Dolutegravir Sodium
Concentration unit: mg milligram(s)
Concentration type: equal
Conce
Sponsors
FUNDACIÓ LLUITA CONTRA LA SIDA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =18 years. 2. Documented HIV-1 infection (confirmed by a NAT/PCR test). 3. Naïve to cART (Pre-exposure prophylaxis with FTC/TDF or TAF/FTC or post-exposure prophylaxis will be allowed if more than 4 weeks before the screening visit). 4. Willing and able to be adherent to antiretroviral therapy for the duration of the study. 5. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study. 6. In the opinion of the principal investigator or designee, the participant has understood the information provided and capable of giving written informed consent. 7. If female in fertile age and heterosexually active; using an effective method of contraception (hormonal contraception, intra-uterine device (IUD), or anatomical sterility in self or partner*) from 14 days prior to the first study product administration until at least 12 weeks after the last study product administration; all female participants must be willing to undergo urine pregnancy tests at time points specified in the Schedule of Procedures. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 44 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Exposure to any antiretroviral drug within the 4 weeks prior to the screening visit. 2. HIV-1 RNA in plasma >500,000 copies/mL. 3. Active AIDS-defining illness within the prior 4 weeks. 4. Chronic hepatitis B (positive HBsAg). 5. Chronic hepatitis C (positive IgG HCV confirmed by positive HCV RNA in plasma). 6. Estimated glomerular filtration rate (eGFR) <50 mL/min. 7. Advance liver function impairment (Child-Pugh C). 8. Use of systemic chemotherapy within the 12 months before the screening visit. 9. Use of systemic corticosteroids during more than 7 consecutive days within the 3 months before the screening visit. 10. Concomitant treatment with co-medications with known drug-drug interactions with study drugs. 11. History or clinical manifestations of any physical or psychiatric disorder which could impair the subject’s ability to complete the study. 12. Any other current or prior therapy which, in the opinion of the investigators, would make the individual unsuitable for the study or influence the results of the study. 13. In women, pregnancy or breastfeeding.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare changes in the HIV-1 reservoir (proviral HIV-1 DNA in CD4+ T cells) from baseline to week 48 between first-line treatment with DTG+3TC versus DTG +FTC/TAF.;Secondary Objective: •To compare the following variables during the study period between the two study arms: Plasma viremia decay. - Proportion of participants with HIV-1 RNA in plasma < 50 copies/mL and < 1 copy/mL. - Changes in CD4/CD8. - Changes in cell-associated HIV-1 RNA in CD4+ T cells. - Changes in plasma and cell-associated p24 . - Changes in activation (HLA-DR/CD38) and exhaustion (PD-1/TIGIT) markers in different lymphocyte subsets defined by CD3/CD4/CD8/CDR7/CD45RA and CD27 surface markers by multiparametric Flow cytometry. - Change in Inflammatory markers (sCD14, CRP, IL-6, IL-10, d-dimer, IP-10, sCD163, LFABP and TRAIL) in plasma. •To evaluate DTG, TFV, FTC and 3TC penetration and distribution in peripheral lymph node. •To evaluate the longitudinal and spatial association between drug distribution and cell-associated HIV- 1 RNA and DNA expression within peripheral lymph node. •To evaluate the resistance-associated mutations in those patients who develop virologic failure.;Primary end point(s): Change in proviral HIV-1 DNA in CD4+ Tcells from baseline to week 48.;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Comparative dynamics of plasma viremia decay during the study period. 2. Proportion of participants with HIV-1 RNA in plasma below 50 copies/mL and below 1 copy/mL at 48 weeks. 3. Changes in the ratio CD4/CD8. 4. Change in cell-associated HIV-1 RNA in CD4+ T cells from baseline to week 48. 5. Change in plasma and cell-associated p24 (single molecule assay) from baseline to week 48. 6. Change in activation (HLA-DR/CD38) and exhaustion (PD-1/TIGIT) markers from baseline to week 48 indifferent lymphocyte subsets defined by CD3/CD4/CD8/CDR7/CD45RA and CD27 surface markers by multiparametric Flow cytometry. 7. Change in inflammatory markers (sCD14, CRP, IL-6, IL-10, d-dimer, IP-10, sCD163, LFABP and TRAIL) from baseline to week 48. 8. DTG, TFV, FTC and 3TC penetration and distribution in peripheral lymph node. 9. Longitudinal and spatial association between drug distribution and cell-associated HIV-1 RNA and DNA expression within peripheral lymph node from baseline to week 48. 10. Resistance-associated mutations in those patients who develop virologic failure during the study.;Timepoint(s) of evaluation of this end point: Week 48 | — |
Countries
Spain
Contacts
Public ContactClinical Research Associate
Fundació Lluita contra la SIDA
Outcome results
None listed