Clinical trial NCT03160105: Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection (Simpl'HIV)
Official title: Evaluation of a Simplified Strategy for the Long-term Management of HIV Infection: a Non-inferiority, Randomized, Controlled, Open-label Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV-1-infection
Antiretroviral Therapy
Maintenance Therapy
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2017-05-19
Enrollment: 186
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
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%.
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Efficacy of DTG-based maintenance therapy (< 100 copies/ml)
timeFrame: 48 weeks
measure: Costs of a patient-centered ART monitoring
timeFrame: 48 weeks
Secondary outcomes:
measure: Efficacy of DTG-based maintenance therapy (<50 copies/ml)
timeFrame: 48 weeks
measure: Efficacy of DTG-based therapy (<50 copies/ml) by FDA snapshot analysis
timeFrame: 48 weeks
measure: HIV-RNA >100 copies/ml as time to loss of virological response (TLOVR)
timeFrame: 48 weeks
measure: Change in CD4 cell count
timeFrame: 48 weeks
measure: Change in HIV-DNA
timeFrame: 48 weeks
measure: Change in lipidic profile
timeFrame: 48 weeks
measure: Change in glucose profile
timeFrame: 48 weeks
measure: Change in Framingham-calculated cardiovascular risk
timeFrame: 48 weeks
measure: Change in glomerular function rate
timeFrame: 48 weeks
measure: Proportion of patients with an adverse event
timeFrame: 48 weeks
measure: Proportion of patients with a severe adverse event
timeFrame: 48 weeks
measure: Proportion of patients with CNS adverse event
timeFrame: 48 weeks
measure: Proportion of patients new to DTG with CNS symptoms
timeFrame: 6 weeks
measure: PROQOL questionnaire
timeFrame: 48 weeks
measure: Patient's monitoring satisfaction for pts in the patient-centered monitoring arm
timeFrame: 48 weeks
measure: Global satisfaction of the monitoring
timeFrame: 48 weeks
measure: Proportion of patients in the patient-centered monitoring arm expressing willingness to change monitoring options
timeFrame: 48 weeks
measure: Patient's treatment satisfaction at week 48
timeFrame: 48 weeks
measure: ARV treatment in the post study
timeFrame: 48 weeks
measure: Study satisfaction
timeFrame: 48 weeks
measure: Cost-effectiveness of study arms
timeFrame: 48 weeks
measure: Change in patient weight
timeFrame: 48 weeks
measure: Adherence questions
timeFrame: 48 weeks
measure: Number of study-related extra clinical visits
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Basel
city: Bern
country: Switzerland
facility: Departement of Infectious Disease, Bern University Hospital
city: Genève
country: Switzerland
facility: Infectious diseases consultation, University Hospitals of Geneva
city: Lausanne
country: Switzerland
facility: Infectious Diseases Service, Lausanne University Hospital
city: Lugano
country: Switzerland
facility: Department of Infectious Diseases, Lugano Regional Hospital
city: St. Gallen
country: Switzerland
facility: Division of Infectious Diseases and Hospital Epidemiology, Kantonspital St.Gallen
city: Zürich
country: Switzerland
facility: Department of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich
Study officials:
References:
citation: 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.