Patients who present late on during their acquisition of the HIV-1 (Human Immunodeficiency Virus) MedDRA version: 20.0 Level: LLT Classification code 10020192 Term: HIV-1 System Organ Class: 100000004862
Conditions
Sponsors
NEAT ID Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. The ability to understand and sign a written informed consent form (ICF) and must be willing to comply with all study requirements. 2. Male or non-pregnant, non-lactating females. 3. Age = 18 years. 4. Has documented, untreated HIV-1 infection with either: a) AIDS with any CD4 cell count (AIDS-defining conditions are listed within Appendix 3). Or b) Severe bacterial infection (BI)† and must have a CD4 cell count 1000 copies/mL. Or d) Currently receiving treatment for OI‡. i. Subjects with other serious OIs, including other AIDS-defining and AIDS-related OIs for which appropriate therapy other than ART exists are eligible, but Investigator approval must be obtained. ii. Current OI treatment can have been discontinued prior to the start of ART. 5. Have an entry HIV viral load > 1000 copies/mL 6. Have the ability to take oral medications. 7. If female and of childbearing potential, is using effective birth control methods (see Appendix 7) and is willing to continue practising these birth control methods during the trial and for at least 30 days 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. 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 330 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 110
Exclusion criteria
Exclusion criteria: 1. Any therapeutic ARV which commenced less than 2 weeks prior to screening and which study entry was taken for more than 48 hours. 2. Systemic cancer chemotherapy within 30 days prior to study entry, or current treatment for cancer (with the exception of Kaposi’s sarcoma) or lymphoma. 3. Current or anticipated use of contraindicated medications (see Summary of Product Characteristics (SmPC) for Symtuza® and IB for B/F/TAF) or anticipated systemic chemotherapy during study enrolment (administration of any contraindicated medication must be discontinued at least 30 days prior to the baseline visit and for the duration of the study). 4. Known resistance to the components of study medications (see section 6.1.3 for more details). 5. History or symptoms of advanced renal and/or hepatic impairment. Such as, kidney failure requiring dialysis; eGFR 5 x upper limit of normal (ULN); or, platelet count <50,000. 6. Current drug or alcohol use that, in the opinion of the Investigator, would cause interference with the study. 7. Cryptococcal meningitis or active TB or current or expected treatment requiring Rifampicin or Rifabutin (patients with expected latent TB will have a TB test (IGRAs e.g. ELISPOT, QuantiFERON etc.) at their screening visit). 8. History or presence of allergy to the study drugs or their components, or drugs of their class. 9. Using any concomitant therapy disallowed as per the reference safety information (RSI) and product labelling for the study drugs. 10. Any investigational drug within 30 days prior to the study drug administration. 11. Patients with severe (Child Pugh class C) hepatic impairment. 12. Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To demonstrate an Integrase Inhibitor containing regimen is no better than a boosted Protease Inhibitor regimen in patients with advanced HIV infection. If the integrase inhibitor regimen is proved to be no better then, we would like to demonstrate whether the Integrase inhibitor regime is superior to the Protease Inhibitor containing regimen.;Secondary Objective: 1. To investigate the incidence of the following clinical events; immunological and virological response, tolerability, resistance development, discontinuation of therapy due to tolerability, quality of life and Immune Reconstitution Inflammatory Syndrome (IRIS). 2. To assess whether virological response is better predicted by next generation deep sequencing rather than the standard population sequencing currently performed.;Primary end point(s): Time to failure, as the first occurrence of any of the following components: 1. Virological reasons: a) Virological failure, defined as insufficient virological response (specifically HIV-1 RNA reduction 50 HIV-1 RNA copies/mL at week 48); or viral rebound, defined as rebound > 1 log 10 copies/mL of any post baseline HIV-1 RNA nadir > 400 copies/mL; or defined as rebound in HIV-1 RNA to >200 copies/mL after having achieved HIV-1 RNA <50 copies/mL, which is subsequently confirmed at the following scheduled or unscheduled visit. 2. Clinical reasons: a) Death related to HIV, AIDS, OI/severe BI or complications of therapy including IRIS b) Any new or recurrent AIDS defining event c) Any new serious non-AIDS defining event documented by the endpoint review committee (including severe BI, liver cirrhosis, renal failure, cardiovascular event, and non-AIDS related malignant disease) d) Clinically relevant AEs of any grade which require treatment interruption of INI or boosted PI therapy within the first 48 weeks after randomisation (discontinuation of BIC or boosted DRV followed by continuation with another INI or PI, respectively, is not considered as | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Proportion of patients with HIV-RNA viral load 200/µL (first measurement) Proportion of patients with CD4 cell count < 200 µL and < 350µL at week 4, 8, 12, 24, 36, 48 CD4/CD8 ratio at week 4, 8, 12, 24, 36, 48 Incidence of IRIS in the two arms through week 48 Incidence and duration of hospitalisation, rate of relapse of specific OI/BI through week 48 Safety and tolerability, measured by Grade 2, 3 and 4 signs and symptoms and laboratory toxicities through week 48 ART and OI/BI treatment changes and dose modifications due to toxicities and DDI with ART, and IRIS through week 48 Health care resource use, including total inpatient days and emergency room visits through week 48 QOL and functional status outcomes, including overall self-reported QOL and functional status compared in the two groups at week 48 Discontinuation or modification of study medication due to insufficient virological response or resistance mutation development before week 48 ;Timepoint(s) of evaluation of this end point: Each timepoint is listed above | — |
Countries
France, Spain, United Kingdom
Contacts
Public ContactCarl Fletcher
Research Organisation (KC) Ltd
Outcome results
None listed