Effectiveness of a dual therapy based on dolutegravir plus lamivudine on reduction of the viral reservoir, immune recovery and immune activation compared with a triple antiretroviral therapy based on dolutegravir plus tenofovir alafenamide/emtricitabine in patients with HIV infection without prior treatment.

INTERVENTION: 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/1/13/892/001 or EU/1/13/892/002 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 50‐ Trade Name: Lamivudine Teva Product Name: Dolutegravir Product Code: EMEA/H/C/002753 Pharmaceutical Form: Pastille INN or Proposed INN: LAMIVUDINE CAS Number: 134678‐17‐4 Current Sponsor code: EMEA/H/C/001113 Other descriptive name: 3TC Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ Trade Name: Descovy Product Name: Tenofovir alafenamida and Emtricitabina Pharmaceutical Form: INN or Proposed INN: EMTRICITABINE CAS Number: 143491‐57‐0 Current Sponsor code: EU/1/16/1099/003 Other descriptive name: FTC Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 200‐ INN or Proposed INN: TENOFOVIR ALAFENAMIDE CAS Number: 379270‐37‐8 Current Sponsor code: EU/1/16/1099/003 Other descriptive name: TAF Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 25‐ CONDITION: 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 Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: ; 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).; 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. 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 OUTCOME: ; 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. INCLUSION CRITERIA: ? Treatment‐naïve HIV‐1‐infected patients = 18 years of age. ? Plasma HIV‐1 RNA >5000 and <500.000 copies/ml. ? T lymphocyte CD4+ count in peripheral blood >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 <1% per year (not all intrauterine devices meet this criterion) o Male partner sterilization confirmed prior to the female subject’s entry into the