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

Calmy Alexandra

Status and phase: Completed; Phase 4

Conditions: Maintenance Therapy; HIV-1-infection; Antiretroviral Therapy

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03160105

CCER 2016-02210

Details and patient eligibility

About

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.

Full 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.

Enrollment: 186 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: None (Open label)

---

186 participants in 4 patient groups

Continuing cART + Standard monitoring

No Intervention group

Description:

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 group

Description:

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

Treatment:

Other: Patient-centered monitoring

Switch to DTG+FTC + Standard monitoring

Experimental group

Description:

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

Treatment:

Drug: Switch to DTG + FTC

Switch to DTG+FTC + Patient-centered monitoring

Experimental group

Description:

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

Treatment:

Drug: Switch to DTG + FTC

Other: Patient-centered monitoring