HIV infection
Conditions
Interventions
Trade Name: Tivicay
Product Name: Dolutegravir
Pharmaceutical Form: Tablet
INN or Proposed INN: Dolutegravir
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 50-
Tr
Sponsors
St Stephen's AIDS Trust
NEAT-ID
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is male or female aged over 50, OR aged over 18 years with a Framingham risk score above 10% 2. Has documented HIV-1 infection 3. Has signed the Informed Consent Form voluntarily 4. Is willing to comply with the protocol requirements 5. Has been receiving an ARV regimen containing a boosted PI (darunavir, atazanavir, lopinavir, saquinavir, or fosamprenavir) plus 2NRTIs for >24 weeks 6. Has stable virological suppression (plasma HIV-RNA 24 weeks) 7. If female and of childbearing potential, is using effective birth control methods (see appendix 4) and is willing to continue practising these birth control methods during the trial and for at least 2 weeks after the last dose of study medication. Note: Non-childbearing potential is defined as either post-menopausal (12 months of spontaneous amenorrhoea and =45 years) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy 8. If a heterosexually active male, he is using effective birth control methods and is willing to continue practising these birth control methods during the trial and until follow-up visit Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 350 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70
Exclusion criteria
Exclusion criteria: 1. Infected with HIV-2 2. Using any concomitant therapy disallowed as per the reference safety information and product labelling for the study drugs 3. Has acute viral hepatitis including, but not limited to, A, B, or C 4. Has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Subjects can enter trial with chronic HBV if HBV-DNA undetectable at screen (and no detectable result in last 6 months) and with chronic HCV if not expected to require treatment during the trial period. 5. Any investigational drug within 30 days prior to the trial drug administration 6. Any prior evidence of primary viral resistance (if a resistance test is available) based on the presence of any major resistance-associated mutation to backbone NRTI 7. History of prior virological failure, eg 2 consecutive HIV-1 RNA >50 c/ml -at or after week 32 following first ART initiation or confirmed rebound viraemia >200 copies/ml after having a VL of 35% direct bilirubin. 10. Unstable liver disease (as defined by the presence of ascities, encephalopathy, coagulopathy, hypoalbuminemia, esophagael or gastic varices, or persistent jaundice), know biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones)) 11. Subjects with severe hepatic impairment (Class C) as determined by Child-Pugh classification (see appendix 5) 12. If female, currently pregnant or breastfeeding 13. Opportunistic infection within 4 weeks prior to first dose of DTG 14. Clinical decision that a switch of antiretroviral therapy should be immediate 15. Screening blood result with any grade 3/4 toxicity according to Division of AIDS (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed). 16. Any condition (including illicit drug use or alcohol abuse) or laboratory results which, in the investigator’s opinion, interfere with assessments or completion of the trial. 17. History or presence of allergy to the study drug or their components
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate continued virus suppression in individuals switching from a boosted PI containing regimen to a dolutegravir containing regimen after 48 weeks To investigate the change in total cholesterol in individuals switching from a boosted PI containing regimen to a a dolutegravir containing regimen after 48 weeks;Secondary Objective: To investigate continued virus suppression in individuals switching from a boosted PI containing regimen to a dolutegravir containing regimen after 24 and 96 weeks To assess the change in CD4 count in individuals switching from a boosted PI containing regimen to a dolutegravir containing regimen To investigate the change in total cholesterol in individuals switching from a boosted PI containing regimen to a a dolutegravir containing regimen after 24 and 96 weeks To assess change in cardiovascular risk in individuals switching from a boosted PI containing regimen to a dolutegravir containing regimen after 48 and 96 weeks, as determined by - lipid values (fats in the blood) - Framingham and DAD scores (these are scores of your cardiovascular risk; this involves putting your age and other basic factors into a table and using a computer to calculate a risk score. The higher your score, the more at risk you are from devloping cardiovascular diseases such as high blood pressure).;Primary end point(s): Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) after 48 weeks Change from baseline in total cholesterol at week 48 ;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Maintenance of virological suppression (ie HIV-1 RNA <50 c/ml) at week 24 and 96 - Change in CD4 count from baseline to week 24, 48 and 96 - Change from baseline in total cholesterol at weeks 24 and 96 - Change from baseline to lipid values (LDL, HDL, triglycerides and TC:HDL ratio) and Framingham and DAD scores at weeks 24, 48 and 96 - Safety (clinical and laboratory adverse events) and tolerability (EuroQoL questionnaire) at weeks 24, 48 and 96 -Change from baseline to arterial stiffness augmentation index at weeks 48 and 96 -Change from baseline to average thickness of common carotid artery walls at weeks 48 and 96 ;Timepoint(s) of evaluation of this end point: 24, 48 and 96 weeks | — |
Countries
Belgium, Italy, Spain, United Kingdom
Contacts
Public ContactGardiner
St Stephen's AIDS Trust
Outcome results
None listed