Early Simplified: A Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection

Treatment Efficacy Clinical Trial

Official title:

A Prospective, Randomised, Controlled, Open-label, Non-inferiority Trial to Compare the Efficacy of Standard of Care Combination Antiretroviral Therapy With a Simplified Dolutegravir Monotherapy in Patients With a Primary HIV-1 Infection Under Suppressive Early Standard of Care Antiretroviral Therapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02551523
• Other study ID #: KEK-ZH-Nr. 2015-0288
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: February 2021

Study information

• Verified date: October 2018
• Source: University of Zurich
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Long term toxicity of combination antiretroviral therapy (cART) is a substantial contributor to morbidity and mortality in chronically infected HIV positive individuals. To date it is still debated, whether long term nucleoside reverse transcriptase inhibitors (NRTI's) -sparing regimens are practicable or even superior compared to standard of care cART in terms of efficacy, safety and tolerability. In addition, data about efficacy of integrase inhibitor (INSTI) based monotherapy is lacking. We aim at investigating the efficacy of standard of care combination antiretroviral therapy with a simplified dolutegravir monotherapy in patients with a primary HIV-1 infection under suppressive early standard of care antiretroviral therapy. Briefly, hundred-thirty-eight patients with a documented primary HIV1- infection (PHI) will be recruited from the Zurich Primary HIV-1 Infection Study (ZHPI), which is an open label, non-randomized, observational, single-center study (http://clinicaltrials.gov, ID 5 NCT00537966). All subjects formerly underwent early cART consisting of either a protease inhibitor (PI) or a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a INSTI in combination with two NRTIs at the time point of enrolment in the ZPHI and must be under a fully suppressive ART (i.e., <50 copies/ml) for at least 48 weeks at the time point of randomisation. The primary end point is the proportion of individuals with a viral failure at week 48 or before.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 101
• Est. completion date: February 2021
• Est. primary completion date: October 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Informed Consent as documented by signature,

• All patients =18 years with a documented primary HIV-infection undergoing standard of care cART (i.e., one active drug from the class of either the PIs, or the NNRTIs, or the INSTIs, in combination with two active drugs from the class of NRTIs) with no previous structured treatment interruption and with a suppressed viral load (defined as 50 copies/ml) during the previous 48 weeks,

• Participant of the Swiss HIV Cohort Study

Exclusion Criteria:

• Patients not willing to sign the informed consent form,

• Presence of =1 major integrase inhibitor resistance associated mutation according to the Sanford algorithm1,

• History of =2 consecutive plasma viremia levels >400 copies/ml at least two weeks apart,

• Ongoing (i.e., replicating) hepatitis B virus infection,

• Hemoglobin < 10 g/dl (men) and < 9 g/dl (women) at the time of enrolment,

• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,

• Women who are pregnant or breast feeding,

• Intention to become pregnant during the course of the study,

• Lack of safe contraception,

• Other clinically significant concomitant disease states (e.g., renal failure, hepatic dysfunction, cardiovascular disease, etc.),

• Known or suspected non-compliance, drug or alcohol abuse,

• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant,

• Participation in another study with investigational drug within the 30 days preceding and during the present study,

• Previous enrolment into the current study,

• Enrolment of the investigator, his/her family members, employees and other dependent persons.

Related Conditions & MeSH terms

• Communicable Diseases
• Dolutegravir
• HIV Infections
• Infection
• Monotherapy
• Primary HIV Infection
• Treatment Efficacy

Intervention

Drug:
• Dolutegravir
92 patients will be simplified to once daily dolutegravir monotherapy
• Standard of care combinational antiretroviral therapy

Locations

Country	Name	City	State
Switzerland	University Hospital Zurich, University of Zurich	Zurich

Sponsors (1)

Lead Sponsor	Collaborator
University of Zurich

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of individuals with a viral failure [defined as =2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before.	The study seeks primarily to determine the efficacy (i.e., proportion of patients with a viral failure [defined as =2 plasma viremia levels >50copies/ml at least two weeks apart] at week 48 or before) of a simplified monotherapy (i.e., DTG) compared to a standard of care HIV triple-therapy in patients with a PHI treated with early ART under long term suppressive ART for at least 48 weeks.	48 weeks
Secondary	Quantification of latent HIV-1 reservoir by measurement of proviral DNA and cell-associated RNA at baseline (time point of randomization), and at week 48		Week48
Secondary	Proportion of individuals with a CSF HIV-1 RNA <50copies/ml in the CSF at week 48 after treatment simplification.		Week 48
Secondary	Proportion of patients with an adverse event at week 48.		Week 48
Secondary	Proportion of patients with a severe adverse event at week 48.		Week 48
Secondary	Time to viral failure (defined as =2 plasma viremia levels >50copies/ml at least two weeks apart) at week 48.		Week 48
Secondary	Proportion of individuals with blips (defined as one viral load >50 and <400 copies/ml with a next viral load <50 copies/ml) at week 48.		Week 48
Secondary	Change from baseline CD4+ cell count from baseline at week 48.		Week 48
Secondary	Proportion of individuals with new onset of proximal tubular renal dysfunction at week 48.		Week 48
Secondary	Creatinine clearance change from baseline at week 48.		Week 48
Secondary	Lipidic profile changes from baseline at week 48.		Week 48
Secondary	Proportion of individuals developing a new CDC-event at week 48.		Week 48
Secondary	Proportion of individuals withdrawing consent at week 48.		Week 48
Secondary	Proportion of individuals being lost to follow-up at week 48.		Week 48
Secondary	Proportion of individuals switching assigned treatment for any cause at week 48.		Week 48