Infection with human immunodeficiency virus (HIV). MedDRA version: 20.1 Level: LLT Classification code 10008919 Term: Chronic HIV infection System Organ Class: 100000004862
Conditions
Interventions
Trade Name: Tivicay
Product Code: J05AX12
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Dolutegravir
Other descriptive name: DOLUTEGRAVIR
Concentration unit: mg milligram(s)
Concentration ty
Sponsors
FUNDACIÓ CLÍNIC PER A LA RECERCA BIOMÈDICA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Males or females at least 18 years of age. Women of childbearing potential* must have a negative pregnancy test within 10 days prior to randomization into the study and commitment to use at least one of these birth control methods: male or female condom with or without spermicide, cap, diaphragm or sponge with or without spermicide, intrauterine device, bilateral tubal occlusion, vasectomized partner, sexual abstinence during the study. 2.Seropositive for HIV-1 using standard diagnostic criteria. 3.Virologicaly suppressed (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Pregnancy, lactation, or planned pregnancy during the study period. 2. Prior virological failure (? 50 copies/mL in 2 consecutive determinations or >500 copies/mL in one determination) to regimens containing 3TC/FTC or integrase inhibitors. 3. Any mutation conferring resistance to 3TC/FTC or integrase inhibitors if genotypic testing had been previously performed. 4. Nadir CD4 <200 cells/mm3. 5. Any disease or history of disease which, in the opinion of the investigator, might confound the results of the study or pose additional risk to patient treatment. 6. Chronic hepatitis B (HBsAg+) or anticipated need for Hepatitis C virus (HCV) therapy during the study. 7. History or presence of allergy to the study drugs components. 8. ALT =5 times the upper limit of normal (ULN) or ALT =3 x ULN and bilirubin = 1.5 x ULN at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: Changes in CD4 and CD8 T-cell counts. Change in body fat distribution Change in lumbar and femoral BMD Change in plasma 25-OH vitamin D levels Change in CKD-EPI and proteinuria (urinary protein/creatinine) Changes in liver profile The grade 3-4 AE and the rate of patients who early withdrawal the study Changes in immune activation, inflammation and mononuclear activation markers Change in sleep quality Change in self-reported adherence In case of virological failure, to assess the emergence of antiretroviral resistance mutations and minority variants (in cellular HIV DNA at baseline) Blips (>50 copies/mL in one detremination preceded and followed by consecutive determinations <50copies/mL) To assess changes in Cerebrospinal fluid (CSF): cells and chemistry including IgG/albumin ratio, HIV RNA, markers of inflammation (neopterin, sCD163) and neuronal damage (neurofilament);Main Objective: To assess the virological efficacy at week 48 of the bitherapy dolutegravir plus lamivudine and the monotherapy dolutegravir in comparison with a triple antiretroviral regimen. After the amendment approval, the main objective is: To assess the virological failure at week 48 of the bitherapy dolutegravir plus lamivudine in comparison with a triple antiretroviral regimen.;Primary end point(s): Therapeutic efficacy and virological failure rate (FDA snapshot algorithm) assessed with standard plasma HIV-1 RNA detection (limit of detection 50 copies/mL) at 48 weeks;Timepoint(s) of evaluation of this end point: 48 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Blips (> 50 copies/mL in one determination preceded and followed by consecutive determinations <50 copies/mL). Efficacy assessed with ultrasensitive HIV-1 RNA detection (limit of detection 1 copy/mL). Change in peripheral mononuclear blood cells HIV-1 reservoir. Change in body fat distribution (DEXA). Change in lumbar and femoral bone mineral density (DEXA). Change in plasma 25-OH vitamin D levels. Change in estimated glomerular filtration rate (CKD-EPI) and proteinuria (urinary protein/creatinine). Changes in CD4 and CD8 cells. Changes in immune activation markers including CD38 and HLA-DR. Changes in biomarkers of inflammation (IL-6, high sensitivity C-reactive protein) and biomarkers of mononuclear activation (SD-14, SD-163). Change in sleep quality (Pittsburgh Sleep Quality Index - see: http://www.medigraphic.com/pdfs/gaceta/gm-2008/gm086e.pdf). Change in self-reported addherence SERAD adherence questionnaire. In case of virological failure, genotypic testing of plasma HIV RNA at failure and assessment of minority variants in cellular HIV DNA at baseline Substudy: In subgroup of patients (20) in bitherapy arm, lumbar puncture at baseline and at 48 weeks will be performed and the following parameters will be measured in Cerebrospinal fluid (CSF): cells and chemistry including IgG/albumin ratio, HIV RNA, markers of inflammation (neopterin, sCD163) and neuronal damage (neurofilament);Timepoint(s) of evaluation of this end point: Changes will be measured between baseline and week 48 | — |
Countries
Spain
Contacts
Public ContactClinical Research Associates
Fundació Lluita contra la SIDA
Outcome results
None listed