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

Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial

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.

Study Overview

• Status: Completed
• Conditions: Antiretroviral Therapy; HIV-1-infection; Maintenance Therapy
• Intervention / Treatment: Other: Patient-centered monitoring; Drug: Switch to DTG + FTC

Detailed Description

This is a pragmatic multicentre, 2x2 factorial randomized controlled trial with 1:1:1:1 randomization to switching to DTG-based maintenance dual therapy in association with FTC or continuation of cART, and to patient-centered monitoring or continuation of standard monitoring.

Patients will be followed during 48 weeks.

• Study Type: Interventional
• Enrollment (Actual): 186
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel
  • Bern, Switzerland
    • Departement of Infectious Disease, Bern University Hospital
  • Genève, Switzerland
    • Infectious diseases consultation, University Hospitals of Geneva
  • Lausanne, Switzerland
    • Infectious Diseases Service, Lausanne University Hospital
  • Lugano, Switzerland
    • Department of Infectious Diseases, Lugano Regional Hospital
  • St. Gallen, Switzerland
    • Division of Infectious Diseases and Hospital Epidemiology, Kantonspital St.Gallen
  • Zürich, Switzerland
    • Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Informed consent as documented by signature;
2. Documented HIV-1 infection;
3. Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
4. ≥ 18 years of age;
5. 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.

6. On standard cART at the time of inclusion, i.e.:

   • 2 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.

Exclusion Criteria:

1. HIV-2 infection;

2. 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;

3. Creatinine clearance < 50ml/min;
4. ASAT or ALAT >2.5x upper limit of the norm;
5. Known hypersensitivity, intolerance or allergy to DTG or FTC;
6. Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months;
7. Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
8. Women who are pregnant or breast-feeding;

9. a. Presence of any INSTI-resistance. Non-availability of INSTI resistance testing is NOT an exclusion criteria.

   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;

10. Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Continuing cART + Standard monitoring; 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.
Experimental: Continuing cART + Patient-centered monitoring; 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; 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
Experimental: Switch to DTG+FTC + Standard monitoring; 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 from standard cART to DTG + FTC dual maintenance therapy.
Experimental: Switch to DTG+FTC + Patient-centered monitoring; 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	Other: Patient-centered monitoring; 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; Drug: Switch to DTG + FTC; Switch from standard cART to DTG + FTC dual maintenance therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of DTG-based maintenance therapy (<50 copies/ml)	Proportion of patients maintaining HIV-RNA <50 copies/ml throughout 48 weeks	48 weeks
Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis	Proportion of patients with HIV-RNA < 50 cp/ml at week 48	48 weeks
HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)	defined as the first of the two-confirmed HIV-RNA >100 copies/ml (at least two weeks apart)	48 weeks
Change in CD4 cell count	from baseline to week 48	48 weeks
Change in HIV-DNA	from baseline to week 48	48 weeks
Change in lipidic profile	from baseline to week 48	48 weeks
Change in glucose profile	from baseline to week 48	48 weeks
Change in Framingham-calculated cardiovascular risk	from baseline to week 48	48 weeks
Change in glomerular function rate	from baseline to week 48	48 weeks
Proportion of patients with an adverse event	throughout week 48	48 weeks
Proportion of patients with a severe adverse event	throughout week 48	48 weeks
Proportion of patients with CNS adverse event	throughout week 48	48 weeks
Proportion of patients new to DTG with CNS symptoms	at 2 and 6 week	6 weeks
PROQOL questionnaire	from baseline to weeks 12 and 48	48 weeks
Patient's monitoring satisfaction for pts in the patient-centered monitoring arm	from baseline to weeks 24 and 48	48 weeks
Global satisfaction of the monitoring	at week 48	48 weeks
Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options	Monitoring satisfaction throughout 48 weeks	48 weeks
Patient's treatment satisfaction at week 48	at week 48	48 weeks
ARV treatment in the post study	ART decided to be used in the post study period	48 weeks
Study satisfaction	at week 48	48 weeks
Cost-effectiveness of study arms	at week 48	48 weeks
Change in patient weight	from baseline to week 48	48 weeks
Adherence questions	Patient adherence to treatment throughout 48 weeks of follow-up	48 weeks
Number of study-related extra clinical visits	performed outside trial scheduled throughout 48 weeks	48 weeks

Collaborators and Investigators

• Sponsor: Calmy Alexandra

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): May 19, 2017
• Primary Completion (Actual): April 18, 2018
• Study Completion (Actual): May 20, 2019

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 18, 2017
• First Posted (Actual): May 19, 2017

Study Record Updates

• Last Update Posted (Actual): August 29, 2019
• Last Update Submitted That Met QC Criteria: August 28, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Infections; Communicable Diseases
• Other Study ID Numbers: CCER 2016-02210

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No