Early Simplified: A Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection

NCT ID: NCT02551523

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-30
• Study Completion Date: 2021-02-28

Brief Summary

Long term toxicity of combination antiretroviral therapy (cART) is a substantial contributor to morbidity and mortality in chronically infected HIV positive individuals. To date it is still debated, whether long term nucleoside reverse transcriptase inhibitors (NRTI's) -sparing regimens are practicable or even superior compared to standard of care cART in terms of efficacy, safety and tolerability. In addition, data about efficacy of integrase inhibitor (INSTI) based monotherapy is lacking. We aim at investigating the efficacy of standard of care combination antiretroviral therapy with a simplified dolutegravir monotherapy in patients with a primary HIV-1 infection under suppressive early standard of care antiretroviral therapy. Briefly, hundred-thirty-eight patients with a documented primary HIV1- infection (PHI) will be recruited from the Zurich Primary HIV-1 Infection Study (ZHPI), which is an open label, non-randomized, observational, single-center study (http://clinicaltrials.gov, ID 5 NCT00537966). All subjects formerly underwent early cART consisting of either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a INSTI in combination with two NRTIs at the time point of enrolment in the ZPHI and must be under a fully suppressive ART (i.e., <50 copies/ml) for at least 48 weeks at the time point of randomisation. The primary end point is the proportion of individuals with a viral failure at week 48 or before.

Conditions

Monotherapy; Dolutegravir; Primary HIV Infection; Treatment Efficacy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Standard of care combination antiretroviral therapy

46 patients will go on with standard of care combination antiretroviral therapy consisting of either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor or a integrase inhibitor in combination with two nucleoside reverse transcriptase inhibitors.

Group Type: ACTIVE_COMPARATOR

Standard of care combinational antiretroviral therapy

Intervention Type: DRUG

Dolutegravir monotherapy

92 patients will be simplified to once daily dolutegravir monotherapy.

Group Type: EXPERIMENTAL

Dolutegravir

Intervention Type: DRUG

92 patients will be simplified to once daily dolutegravir monotherapy

Interventions

Dolutegravir

92 patients will be simplified to once daily dolutegravir monotherapy

Intervention Type: DRUG

Standard of care combinational antiretroviral therapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed Consent as documented by signature,
• All patients ≥18 years with a documented primary HIV-infection undergoing standard of care cART (i.e., one active drug from the class of either the PIs, or the NNRTIs, or the INSTIs, in combination with two active drugs from the class of NRTIs) with no previous structured treatment interruption and with a suppressed viral load (defined as 50 copies/ml) during the previous 48 weeks,
• Participant of the Swiss HIV Cohort Study

Exclusion Criteria

• Patients not willing to sign the informed consent form,
• Presence of ≥1 major integrase inhibitor resistance associated mutation according to the Sanford algorithm1,
• History of ≥2 consecutive plasma viremia levels >400 copies/ml at least two weeks apart,
• Ongoing (i.e., replicating) hepatitis B virus infection,
• Hemoglobin < 10 g/dl (men) and < 9 g/dl (women) at the time of enrolment,
• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• Lack of safe contraception,
• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),
• Known or suspected non-compliance, drug or alcohol abuse,
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominique L Braun, MD

Role: PRINCIPAL_INVESTIGATOR

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich

Locations

University Hospital Zurich, University of Zurich

Zurich, , Switzerland

Countries

Switzerland

References

Braun DL, Turk T, Tschumi F, Grube C, Hampel B, Depmeier C, Schreiber PW, Brugger SD, Greiner M, Steffens D, De Torrente-Bayard C, Courlet P, Neumann K, Kuster H, Flepp M, Bertisch B, Decosterd L, Boni J, Metzner KJ, Kouyos RD, Gunthard HF. Noninferiority of Simplified Dolutegravir Monotherapy Compared to Continued Combination Antiretroviral Therapy That Was Initiated During Primary Human Immunodeficiency Virus Infection: A Randomized, Controlled, Multisite, Open-label, Noninferiority Trial. Clin Infect Dis. 2019 Oct 15;69(9):1489-1497. doi: 10.1093/cid/ciy1131.

Reference Type: DERIVED

PMID: 30601950 (View on PubMed)

Other Identifiers

KEK-ZH-Nr. 2015-0288

Identifier Type: -

Identifier Source: org_study_id