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

HIV-1-infection Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03160105
• Other study ID #: CCER 2016-02210
• Status: Completed
• Phase: Phase 4
• Start date: May 19, 2017
• Est. completion date: May 20, 2019

Study information

• Verified date: August 2019
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: May 20, 2019
• Est. primary completion date: April 18, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Antiretroviral Therapy
• Communicable Diseases
• HIV Infections
• HIV-1-infection
• Infection
• Maintenance Therapy

Intervention

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

Locations

Country	Name	City	State
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

Sponsors (1)

Lead Sponsor	Collaborator
Calmy Alexandra

Country where clinical trial is conducted

Switzerland, 

Outcome

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