Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV)

NCT03160105 | Completed Phase 4 DMC

• 1 other identifier: CCER 2016-02210
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to evaluate whether maintenance antiretroviral therapy could be simplified to DTG + FTC dual therapy and/or patient-centered monitoring once virological suppression is achieved. Using a factorial design, the study aims to assess the efficacy of DTG + FTC dual therapy to maintain virological suppression through 48 weeks of follow-up as well as the costs of a patient-centered ART laboratory monitoring.

Conditions

HIV-1-infection; Antiretroviral Therapy; Maintenance Therapy

Outcome Measures

Primary Outcomes (2)

• Efficacy of DTG-based maintenance therapy (< 100 copies/ml)

  Proportion of patients maintaining HIV-RNA \<100 copies/ml throughout 48 weeks

  48 weeks

• Costs of a patient-centered ART monitoring

  Direct costs of the two study arms from the health care system perspective at week 48

  48 weeks

Secondary Outcomes (24)

• Efficacy of DTG-based maintenance therapy (<50 copies/ml)

  48 weeks

• Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis

  48 weeks

• HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)

  48 weeks

• Change in CD4 cell count

  48 weeks

• Change in HIV-DNA

  48 weeks

Study Arms (4)

Continuing cART + Standard monitoring

NO INTERVENTION

Patients randomized to this arm will continue their current standard ART regimen (cART) and will continue a standard 3-monthly routine safety biological monitoring (including CD4 cell count, fasting lipids and glucose, renal and hepatic function tests) at their SHCS site.

Continuing cART + Patient-centered monitoring

EXPERIMENTAL

Patients randomized to this arm will continue their current cART and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36

Other: Patient-centered monitoring

Switch to DTG+FTC + Standard monitoring

EXPERIMENTAL

Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed once per year and at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36

Drug: Switch to DTG + FTC

Switch to DTG+FTC + Patient-centered monitoring

EXPERIMENTAL

Patients randomized to this arm will be switched to DTG + FTC dual maintenance therapy and will have immunological and safety blood examinations performed at screening and at week 48. In addition, patients will be ask to choose at least one of the following alternative options for weeks 6, 12 and 36: decentralised venipuncture and blood tests, delivery of ARV drugs by mail and Assessment and clinical interview by phone or skype call

Drug: Switch to DTG + FTC; Other: Patient-centered monitoring

Interventions

Switch to DTG + FTC DRUG

Switch from standard cART to DTG + FTC dual maintenance therapy.

Switch to DTG+FTC + Patient-centered monitoring; Switch to DTG+FTC + Standard monitoring

Patient-centered monitoring OTHER

Immunological and safety blood examinations performed only once per year at least one options (decentralised venipuncture and blood tests, delivery of ARV drugs by mail and interview by phone or skype call) for weeks 6, 12 and 36

Continuing cART + Patient-centered monitoring; Switch to DTG+FTC + Patient-centered monitoring

Eligibility Criteria

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

You may qualify if:

• Informed consent as documented by signature;
• Documented HIV-1 infection;
• Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
• ≥ 18 years of age;
• HIV-RNA \<50 copies/mL at screening and for at least 24 weeks before screening on effective suppressive cART, one blip with less than 200 copies/mL being allowed during this period if followed by at least 2 results \< 50 copies/mL.
• NRTIs + either 1 NNRTI, 1 boosted PI or 1 INSTI;
• NRTI-sparing triple ARV regimen (e.g. 1 NRTI + 1 NNRTI + 1 InSTI);
• Dual therapy with protease inhibitor.

You may not qualify if:

• HIV-2 infection;
• Previous ART change for unsatisfactory virological response, i.e. slow initial virological suppression, incomplete suppression or rebound. Change of drug or drug class for convenience or toxic effect prevention or management is allowed.
• Note: patients with documented genotype(s) presenting only a M184V mutation remain eligible;
• Creatinine clearance \< 50ml/min;
• ASAT or ALAT \>2.5x upper limit of the norm;
• Known hypersensitivity, intolerance or allergy to DTG or FTC;
• Known or suspected non-adherence (defined as \<80% adherence, i.e. missed doses \> 1x/week) to current treatment in the last 6 months;
• Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
• Women who are pregnant or breast-feeding;
• b. Non availability of previous routine resistance test, at least for reverse transcriptase and protease genes.
• Note: Subjects remain eligible in the absence of any previous resistance test only if they are on their first-line antiretroviral regimen;
• Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.

Sponsors & Collaborators

• Calmy Alexandra: lead

Study Sites (7)

Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel

Basel, Switzerland

Location

Departement of Infectious Disease, Bern University Hospital

Bern, Switzerland

Location

Infectious diseases consultation, University Hospitals of Geneva

Geneva, Switzerland

Location

Infectious Diseases Service, Lausanne University Hospital

Lausanne, Switzerland

Location

Department of Infectious Diseases, Lugano Regional Hospital

Lugano, Switzerland

Location

Division of Infectious Diseases and Hospital Epidemiology, Kantonspital St.Gallen

Sankt Gallen, Switzerland

Location

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

Zurich, Switzerland

Location

Related Publications (2)

• Marinosci A, Sculier D, Wandeler G, Yerly S, Stoeckle M, Bernasconi E, Braun DL, Vernazza P, Cavassini M, Buzzi M, Metzner KJ, Decosterd L, Gunthard HF, Schmid P, Limacher A, Branca M, Calmy A. Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial. Swiss Med Wkly. 2024 Apr 15;154:3762. doi: 10.57187/s.3762.

  PMID: 38754068 DERIVED

• Sculier D, Wandeler G, Yerly S, Marinosci A, Stoeckle M, Bernasconi E, Braun DL, Vernazza P, Cavassini M, Buzzi M, Metzner KJ, Decosterd LA, Gunthard HF, Schmid P, Limacher A, Egger M, Calmy A; Swiss HIV Cohort Study (SHCS). Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL'HIV trial. PLoS Med. 2020 Nov 10;17(11):e1003421. doi: 10.1371/journal.pmed.1003421. eCollection 2020 Nov.

  PMID: 33170863 DERIVED

MeSH Terms

Interventions

Racivir

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: This is a pragmatic multicentre, 2x2 factorial randomized controlled trial with 1:1:1:1 randomization. A sample size of 92 patients in each group will be required to demonstrate non-inferiority with a non-inferiority (NI) margin of 12%.

Study Record Dates

• First Submitted: May 16, 2017
• First Posted: May 19, 2017
• Study Start: May 19, 2017
• Primary Completion: April 18, 2018
• Study Completion: May 20, 2019
• Last Updated: August 29, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (7)