The Late Presenter Treatment Optimisation Study

NCT03696160 | Completed Phase 3 Results DMC

• 1 other identifier: NEAT44
• Study Type: interventional
• Target: 447
• Locations: 7 countries
• Sites: 53

Brief 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.

Conditions

HIV/AIDS

Outcome Measures

Primary Outcomes (1)

• Treatment Failure

  Composite outcome: treatment failure due to either virological or clinical reasons. Virological reasons can either be insufficient virological response or viral rebound. Clinical reasons can be death related to HIV/AIDS/opportunistic infection or severe bacterial infection, new or recurrent AIDS defining event, any serious non-AIDS defining event or clinically relevant adverse events of any grade or immune reconstitution inflammatory syndrome requiring treatment

  Earliest at 12 weeks, latest 48 weeks

Secondary Outcomes (12)

• Proportion of Patients With HIV-RNA Viral Load <50 Copies/mL

  Week 24, 36 and 48

• Time to Reach CD4 (Cluster of Differentiation 4) Count >200/µL

  Through study completion, up to 48 weeks.

• Proportion of Patients With CD4 Cell Count <200 and < 350μL at Week 4, 8, 12, 24, 36, 48

  4, 8, 12, 24, 36, 48 weeks

• CD4/CD8 (Cluster of Differentiation 8) Ratio

  Week 4, 8, 12, 24, 36, 48

• Incidence of Immune Reconstitution Inflammatory Syndrome

  Week 48

Study Arms (2)

Biktarvy

EXPERIMENTAL

Bictegravir is an inhibitor of HIV-1 integrase that is being evaluated for the treatment of HIV-1 infection. Biktarvy® received marketing authorisation valid throughout the European Union (EU) in June 2018. Biktarvy is a combination of bictegravir, emtricitabine, and tenofovir (B/F/TAF). Method of administration: One combined B 50mg/F 200mg/TAF 25mg tablet taken orally once daily for up to 48 weeks without regard to food.

Drug: Biktarvy

Symtuza

EXPERIMENTAL

Symtuza® is a boosted PI indicated for the treatment of HIV-1 infection. Symtuza® received marketing authorisation valid throughout the EU in September 2017. Symtuza is a combination of darunavir, cobicistat, emtricitabine and tenofovir alafenamide (D/C/F/TAF) Method of administration: One combined D 800mg/C 150mg/F 200mg/TAF 10mg tablet taken orally once daily for up to 48 weeks with the addition of food.

Drug: Symtuza

Interventions

Biktarvy DRUG

Integrase inhibitor used to treat HIV-1 infection

Biktarvy

Symtuza DRUG

Protease inhibitor used to treat HIV-1 infection

Symtuza

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The ability to understand and sign a written informed consent form (ICF) and must be willing to comply with all study requirements.
• Male or non-pregnant, non-lactating females†.
• Age ≥ 18 years.
• Have documented, untreated HIV-1 infection with either:
• AIDS with any CD4 cell count (AIDS-defining conditions are listed within Appendix 3).
• Severe bacterial infection (BI)‡ and must have a CD4 cell count \< 200/μl within 28 days prior to study entry§.
• Any symptoms or no symptoms and must have a CD4 cell count \< 100/μL within 28 days prior to study entry and must have an entry HIV viral load \> 1000 copies/mL.
• 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 start of ART.
• Have an entry HIV viral load \> 1000 copies/mL
• Have the ability to take oral medications.
• Females of childbearing potential and heterosexually active males must be willing to use a highly effective method of contraception and be willing to continue practising these birth control methods during the trial and for at least 30 days after the last dose of study medication. See Appendix 7 for further details.
• Such methods include:
• True abstinence from penile-vaginal intercourse, when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), and withdrawal are not acceptable methods of contraception).
• Non-hormonal Intrauterine device or non-hormonal intrauterine system that meets the effectiveness criteria as stated in the product label.
• Male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject.

You may not qualify if:

• Any therapeutic ARV which commenced less than 2 weeks prior to screening and which was taken for more than 48 hours
• Systemic cancer chemotherapy within 30 days prior to study entry, or current treatment for cancer (with the exception of Kaposi's sarcoma) or lymphoma.
• Current or anticipated use of contraindicated medications (see Summary of Product Characteristics (SmPC) for Symtuza® and 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).
• Known resistance to the components of study medications (see section 6.1.3 for more details).
• History or symptoms of advanced renal and/or hepatic impairment. Such as, kidney failure requiring dialysis; eGFR \<30 mL/min; hepatic transaminases (AST and ALT) \> 5 x upper limit of normal (ULN); or, platelet count \<50,000.
• Current drug or alcohol use that, in the opinion of the Investigator, would cause interference with the study.
• 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).
• History or presence of allergy to the study drugs or their components, or drugs of their class.
• Using any concomitant therapy disallowed as per the product labelling for the study drugs.
• Any investigational drug within 30 days prior to the study drug administration.
• Patients with severe (Child Pugh class C) hepatic impairment.
• Women who are pregnant, breastfeeding or plan to become pregnant or breastfeed during the study.

Sponsors & Collaborators

• Janssen Pharmaceuticals: collaborator
• NEAT ID Foundation: lead
• Gilead Sciences: collaborator

Study Sites (53)

Institute of Tropical Medicine

Antwerp, Belgium

Location

CHU Saint-Pierre

Brussels, Belgium

Location

University Hospital Ghent

Ghent, Belgium

Location

Hopital Europeen Marseille

Marseille, France

Location

Groupe Hospitalier Sud Ile-de-France (Melun)

Melun, France

Location

Hôpital Gui de Chauliac

Montpellier, France

Location

CHU de Nantes

Nantes, France

Location

Hopital Lariboisiere

Paris, France

Location

Hopital Saint-Louis

Paris, France

Location

Hôpital Saint Antoine

Paris, France

Location

Pitié-Salpêtrière Hospital

Paris, France

Location

Medizinische Klinik und Poliklinik Universitätsklinikum Bonn

Bonn, Germany

Location

University Hospital Koln

Cologne, Germany

Location

Goethe University Hospital Frankfurt

Frankfurt, Germany

Location

University Hospital Geissen

Geißen, Germany

Location

ICH Study Center Gmbh & Co. KG

Hamburg, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

University Hospital Klinikum rechts der Isar der TUM

Munich, Germany

Location

Mater Misericordiae University Hospital

Dublin, Ireland

Location

St Vincent's University Hospital

Dublin, Ireland

Location

Luigi Sacco Hospital

Milan, Italy

Location

Ospedale San Raffaele

Milan, Italy

Location

ASST Santi Paolo

Milan, Italy

Location

Clinica of Infectious Diseases

Modena, Italy

Location

INMI Lazzaro Spallanzani, Rome

Rome, Italy

Location

Hospital General Universatario Alicante

Alicante, Spain

Location

Hospital Bellvitge

Barcelona, Spain

Location

Hospital Clinic (Helios Building)

Barcelona, Spain

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Trias i Pujol

Barcelona, Spain

Location

Hospital Universitari Vall d'Herbon

Barcelona, Spain

Location

Hospital General Universitatrio de Elche

Elche, Spain

Location

Hospital 12 Octubre

Madrid, Spain

Location

Hospital de la Princesa

Madrid, Spain

Location

Hospital Ramon y Cajal

Madrid, Spain

Location

Hospital Universitatrio La Paz

Madrid, Spain

Location

Hospital Virgen de la Victoria

Málaga, Spain

Location

Royal Bournemouth Hospital

Bournemouth, United Kingdom

Location

Southmead Hospital

Bristol, United Kingdom

Location

Leeds Teaching Hospital

Leeds, United Kingdom

Location

Barts Health

London, United Kingdom

Location

Chelsea and Westminister

London, United Kingdom

Location

Guy's Hospital

London, United Kingdom

Location

Homerton University Hospital

London, United Kingdom

Location

Imperial College Healthcare Trust

London, United Kingdom

Location

Kings College London

London, United Kingdom

Location

Mortimer Market Centre

London, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

St George's Hospital

London, United Kingdom

Location

University Hospital Lewisham

London, United Kingdom

Location

North Manchester General Hospital

Manchester, United Kingdom

Location

Sheffield Teaching Hospital

Sheffield, United Kingdom

Location

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MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

bictegravir, emtricitabine, tenofovir alafenamide, drug combination; symtuza

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

The open-label design may have influenced AE reporting, although objective outcomes were adjudicated The 48-week follow-up limits insight into long-term outcomes such as metabolic effects, weight gain, and virological durability. Excluding patients with active tuberculosis or cryptococcal meningitis restricts applicability to high-risk subgroups. The predominantly European cohort may not reflect PWAD in regions with higher burdens of opportunistic infections.

Results Point of Contact

• Title: Project Manager
• Organization: Research Organisation (KC) Ltd

LAPTOP@rokcservices.com

+44 (0) 7508 439711

Study Officials

• Georg Behrens

  Hannover Medical School

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: October 4, 2018
• Study Start: March 5, 2019
• Primary Completion: June 17, 2024
• Study Completion: June 17, 2024
• Last Updated: December 17, 2025
• Results First Posted: December 17, 2025

Record last verified: 2025-12

Locations

GB (15); ES (13); DE (7); IT (5); FR (8); IE (2); BE (3)