Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV)
- Conditions
- Antiretroviral TherapyMaintenance TherapyHIV-1-infection
- Interventions
- Other: Patient-centered monitoringDrug: Switch to DTG + FTC
- Registration Number
- NCT03160105
- Lead Sponsor
- Calmy Alexandra
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 186
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Informed consent as documented by signature;
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Documented HIV-1 infection;
-
Enrolled in the Swiss HIV Cohorte Study (SHCS) or receiving care from a medical doctor of the SHCS network;
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≥ 18 years of age;
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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.
-
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.
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HIV-2 infection;
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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;
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ASAT or ALAT >2.5x upper limit of the norm;
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Known hypersensitivity, intolerance or allergy to DTG or FTC;
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Known or suspected non-adherence (defined as <80% adherence, i.e. missed doses > 1x/week) to current treatment in the last 6 months;
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Concomitant use of drugs that decrease DTG blood concentrations including carbamazepine, oxcarbamazepine, phenytoin, phenobarbital, St John's wort and rifampicin;
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Women who are pregnant or breast-feeding;
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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;
-
Evidence of acute or chronic hepatitis B virus infection based on results of serology testing.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Continuing cART + Patient-centered monitoring 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 Switch to DTG+FTC + Patient-centered monitoring 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 Switch to DTG+FTC + Standard monitoring Switch to DTG + FTC 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 Switch to DTG+FTC + Patient-centered monitoring Switch to DTG + FTC 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
- Primary Outcome Measures
Name Time Method Efficacy of DTG-based maintenance therapy (< 100 copies/ml) 48 weeks Proportion of patients maintaining HIV-RNA \<100 copies/ml throughout 48 weeks
Costs of a patient-centered ART monitoring 48 weeks Direct costs of the two study arms from the health care system perspective at week 48
- Secondary Outcome Measures
Name Time Method Change in HIV-DNA 48 weeks from baseline to week 48
Proportion of patients with a severe adverse event 48 weeks throughout week 48
Change in lipidic profile 48 weeks from baseline to week 48
Global satisfaction of the monitoring 48 weeks at week 48
ARV treatment in the post study 48 weeks ART decided to be used in the post study period
Efficacy of DTG-based maintenance therapy (<50 copies/ml) 48 weeks Proportion of patients maintaining HIV-RNA \<50 copies/ml throughout 48 weeks
Change in CD4 cell count 48 weeks from baseline to week 48
PROQOL questionnaire 48 weeks from baseline to weeks 12 and 48
HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR) 48 weeks defined as the first of the two-confirmed HIV-RNA \>100 copies/ml (at least two weeks apart)
Change in glucose profile 48 weeks from baseline to week 48
Proportion of patients with CNS adverse event 48 weeks throughout week 48
Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis 48 weeks Proportion of patients with HIV-RNA \< 50 cp/ml at week 48
Change in glomerular function rate 48 weeks from baseline to week 48
Proportion of patients new to DTG with CNS symptoms 6 weeks at 2 and 6 week
Patient's monitoring satisfaction for pts in the patient-centered monitoring arm 48 weeks from baseline to weeks 24 and 48
Change in Framingham-calculated cardiovascular risk 48 weeks from baseline to week 48
Proportion of patients with an adverse event 48 weeks throughout week 48
Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options 48 weeks Monitoring satisfaction throughout 48 weeks
Patient's treatment satisfaction at week 48 48 weeks at week 48
Study satisfaction 48 weeks at week 48
Cost-effectiveness of study arms 48 weeks at week 48
Change in patient weight 48 weeks from baseline to week 48
Number of study-related extra clinical visits 48 weeks performed outside trial scheduled throughout 48 weeks
Adherence questions 48 weeks Patient adherence to treatment throughout 48 weeks of follow-up
Trial Locations
- Locations (7)
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
Infectious diseases consultation, University Hospitals of Geneva
🇨🇭Genève, Switzerland
Department of Infectious Diseases, Lugano Regional Hospital
🇨🇭Lugano, Switzerland
Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel
🇨🇭Basel, Switzerland
Infectious Diseases Service, Lausanne University Hospital
🇨🇭Lausanne, Switzerland
Departement of Infectious Disease, Bern University Hospital
🇨🇭Bern, Switzerland