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

• ClinicalTrials.gov Identifier: NCT03160105
• Recruitment Status: Completed
• First Posted: May 19, 2017
• Last Update Posted: August 29, 2019
• Sponsor: Calmy Alexandra
• Information provided by (Responsible Party): Calmy Alexandra, University Hospital, Geneva

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV-1-infection; Antiretroviral Therapy; Maintenance Therapy	Drug: Switch to DTG + FTC; Other: Patient-centered monitoring	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 186 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Intervention Model Description: 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%.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial
• Actual Study Start Date: May 19, 2017
• Actual Primary Completion Date: April 18, 2018
• Actual Study Completion Date: May 20, 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Efficacy of DTG-based maintenance therapy (< 100 copies/ml) [ Time Frame: 48 weeks ]
   Proportion of patients maintaining HIV-RNA <100 copies/ml throughout 48 weeks
2. Costs of a patient-centered ART monitoring [ Time Frame: 48 weeks ]
   Direct costs of the two study arms from the health care system perspective at week 48

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Switzerland

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

Basel, Switzerland

Departement of Infectious Disease, Bern University Hospital

Bern, Switzerland

Infectious diseases consultation, University Hospitals of Geneva

Genève, Switzerland

Infectious Diseases Service, Lausanne University Hospital

Lausanne, Switzerland

Department of Infectious Diseases, Lugano Regional Hospital

Lugano, Switzerland

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

St. Gallen, Switzerland

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

Zürich, Switzerland

Sponsors and Collaborators

Calmy Alexandra

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Sculier D, Wandeler G, Yerly S, Marinosci A, Stoeckle M, Bernasconi E, Braun DL, Vernazza P, Cavassini M, Buzzi M, Metzner KJ, Decosterd LA, Günthard 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.

• Responsible Party: Calmy Alexandra, Professor, University Hospital, Geneva
• ClinicalTrials.gov Identifier: NCT03160105
• Other Study ID Numbers: CCER 2016-02210
• First Posted: May 19, 2017
• Last Update Posted: August 29, 2019
• Last Verified: August 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

Infections; Communicable Diseases; HIV Infections; Disease Attributes; Pathologic Processes; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Immunologic Deficiency Syndromes; Immune System Diseases