Adult patients with HIV infection without previous treatment MedDRA version: 20.1 Level: PT Classification code 10020161 Term: HIV infection System Organ Class: 10021881 - Infections and infestations MedDRA version: 20.1 Level: LLT Classification code 10020160 Term: HIV disease System Organ Class: 10021881 - Infections and infestations
Conditions
Interventions
Trade Name: Tivicay
Product Name: Dolutegravir
Product Code: EMEA/H/C/002753
Pharmaceutical Form: Pastille
INN or Proposed INN: DOLUTEGRAVIR SODIUM
CAS Number: 1051375-16-6
Current Sponsor code: EU/1/
Sponsors
Fundación Pública Andaluza para la Gestión en Salud de Sevilla (FISEVI)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Treatment-naïve HIV-1-infected patients = 18 years of age. ? Plasma HIV-1 RNA >5000 and 200/µl. ? Patients of childbearing age should consent to use a highly effective contraceptive method from 15 days before the time of inclusion of the study until 30 days after the end of it. It is considered a highly effective method: o Complete abstinence from penile-vaginal intercourse from 2 weeks prior to administration of Investigational Product, throughout the study, and for at least 2 weeks after discontinuation of all study medications; o Any intrauterine device with published data showing that the expected failure rate is =65 years) yes F.1.3.1 Number of subjects for this age range 15
Exclusion criteria
Exclusion criteria: ? Acute HIV infection ? T lymphocyte CD4+ count in peripheral blood = 200/µl ? Active opportunistic infection. ? Pregnancy at inclusion or during the follow-up ? Active hepatitis C and/or B virus co-infection. ? ALT = 5 times the ULN, or ALT = 3xULN and bilirubin = 1.5xULN (with >35% direct bilirubin). ? Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (apart from hyperbilirubinemia or jaundice due to Gilbert's syndrome or asymptomatic gallstones). ? Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification. ? Current or past disease that requires the use subsidiary of treatment with corticosteroids, immunomodulatory agents, interferon or chemotherapeutic agents. ? Any laboratory abnormality grade 3 or 4 according to the U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Division of AIDS (Annex 3) ? Concomitant use of drugs with potential major interactions with the prescribed drugs according the respective full prescribing information. ? Estimated creatinine clearance <50ml/min. ? History or presence of allergy to the study drugs or their components
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if a dual therapy based on dolutegravir plus lamivudine (DTG/3TC) will provide a comparable reduction in viral reservoir size than a triple therapy based on dolutegravir plus tenofovir alafenamide / emtricitabine (DTG/F/TAF) after 48 and 96 weeks in treatment-naïve HIV-infected patients.;Secondary Objective: •To evaluate the effect on the immune recovery of triple antiretroviral therapy based on DTG / TAF / F, versus a dual therapy based on dolutegravir plus lamivudine DTG/3TC after 48 and 96 weeks in treatment-naïve HIV-infected patients. •To evaluate if a dual therapy based on DTG/3TC will provide a comparable reduction in immune activation and inflammation than a triple therapy based on DTG/F/TAF after 48 and 96 weeks in treatment-naïve HIV-infected patients. •Evaluate the reduction of the viral load in semen (this objective will be carried out only in a subgroup of patients belonging to the Hospital Virgen Rocío University, which will consist of a minimum of 15 patients per arm). •Evaluate the reduction of the viral reservoir in gut-associated lymphoid tissue (GALT) (this objective will be carried out only in a subgroup of patients belonging to the Hospital Universitario Virgen del Rocío University, which will consist of minimum of, 10 patients per arm).;Primary end point(s): Mean changes in proviral HIV-DNA and HIV-RNA in PBMCs after 48 and 96 weeks of treatment;Timepoint(s) of evaluation of this end point: Changes after 24, 48 and 96 moths of treatment according to variable. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Immune recovery measured as the CD4 + / CD8 + ratio ? Viral reservoir size, evaluated by proviral HIV-DNA in PBMCs. ? Immune activation assessed by the expression of HLA-DR and CD38 in both of CD4+ and CD8+ T. ? Expression of markers for recent thymic emigrants (CD31), proliferation (Ki67), dysfunction (PD-1), senescence (CD57), and apoptosis (annexin V) in both CD4+ and CD8+ T cells. ? Pro-inflammatory soluble mediator in plasma expression (TNF-a, IL-1ß, IL-6, IP-10, IFN- ?, MIP-1a , MIP-1ß, hs-CRP and D-dimers) determined by ELISA. ? Changes in proviral DNA (DNA-HIV) and HIV transcripts (RNA-HIV) in PBMCs and purified CD4 + lymphocytes. ? Monocytes activation (plasma sCD14 and sCD163) ? Decrease of RNA-HIV in seminal plasma.;Timepoint(s) of evaluation of this end point: Changes after 3, 6, 12 and 24 moths of treatment according to variable. | — |
Countries
Spain
Contacts
Public ContactUICEC-HUVR
Unidad de Investigación Clínica y ensayos Clínicos
Outcome results
None listed