The Late Presenter Treatment Optimisation Study

• Status: Recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The main purpose of this study is to compare two different types of HIV treatments, in terms of effectiveness and improvement of side effects, for patients who are diagnosed with a more advanced HIV infection. Patients with advanced HIV infections are otherwise known as 'late presenters'.

There are many effective treatments for HIV available; however, for late presenting patients the investigators do not know which type of treatment performs best. This is the first large study to compare treatments for patients in this situation, and the investigators hope that the results of this study will help doctors decide which treatments to use in the future.

The two different types of treatment the investigators are comparing both contain a mixture of drugs that work together to combat HIV:

The Boosted Protease Inhibitor combination (PI) which is a combination tablet containing:

darunavir, cobicistat, emtricitabine and tenofovir alafenamide. It was approved for use in Europe under the brand name Symtuza®.

The Integrase Inhibitor combination (INI). Which is a combination tablet containing:

bictegravir, emtricitabine and tenofovir alafenamide. This is a a newer combination which was approved for use in Europe in June 2018 under the brand name of Biktarvy®.

The main difference between the two treatments is how each one fights a HIV infection. They both stop a part of the virus from working (i.e. inhibit it), to prevent it from making copies of itself. The PI treatment contains drugs to stop the protease part of the virus, whereas the INI treatment contains drugs to stop the integrase part.

In recent studies, it appears that treatments containing integrase inhibitors may be better for late presenting patients. They have been shown to quickly bring down the amount of virus in the body, and the side effects may be more acceptable to late presenters.

To compare the two treatments, half of the participants on this study will be given the PI treatment, and the other half will be given the INI treatment.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: NEAT ID Foundation
• Collaborators: Gilead Sciences; Janssen Pharmaceuticals
• Treatments: HIV Protease Inhibitors; Integrase Inhibitors; Protease Inhibitors

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:

1. AIDS with any CD4 cell count (AIDS-defining conditions are listed within Appendix 3).

Or

2. Severe bacterial infection (BI) and must have a CD4 cell count < 200/µl within 30 days prior to study entry.

Or

3. Are asymptomatic with CD4 cell count < 100/µL within 30 days prior to study entry and must have an entry HIV viral load > 1000 copies/mL.

Or

4. Currently receiving treatment for opportunistic infection (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 must have been started ≤ 14 days prior to study entry, but can have been discontinued prior to study entry.

5. Have the ability to take oral medications.

6. 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.

7. If a heterosexually active male, is using effective birth control methods 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.

Exclusion Criteria:

1. Any antiretroviral prior to study entry.

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 Investigator's Brochure (IB) for Biktarvy®) 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 (epidermal growth factor receptor) <30 mL/min; hepatic transaminases (AST and ALT) > 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 tuberculosis (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.

13. Females of childbearing potential and heterosexually active males must be willing to use a highly effective method of contraception. See Appendix 7 for further details. Such methods include:

a. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:

i. oral

ii.intravaginal

iii.transdermal

b.progestogen-only hormonal contraception associated with inhibition of ovulation

i.oral

ii. injectable

iii.implantable

c. intrauterine device (IUD)

d. intrauterine hormone-releasing system (IUS)

e. bilateral tubal occlusion

f. vasectomised partner

g. sexual abstinence (with male partners)