A Pilot Study of MONOtherapy of DOlutegravir in HIV-1 Virologically Suppressed Patients (MONODO)

An Interventional, One-arm, Open Label Pilot Study to Assess the Feasibility of Dolutegravir Monotherapy in Virologically Suppressed Patients on Conventional Triple Antiretroviral Therapy of Dolutegravir Plus Two Nucleoside Reverse Transcriptase Inhibitors

Current HIV treatment guidelines recommend a combination of drugs for the maintenance of antiretroviral therapy (ART). Simplification is considered critical to further scale-up of treatment, to support retention in care and to reduce costs. Dolutegravir is a once daily integrase inhibitor that shows very good tolerability, efficacy, and distinctive resistance profile. The researchers aim at investigating the feasibility of dolutegravir monotherapy in maintenance therapy. Briefly, 10 virologically suppressed patients for at least six months on conventional triple ART of dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs) will be switched to dolutegravir monotherapy for 24 weeks. The primary endpoint is the number of patients completing 24 weeks of dolutegravir monotherapy without experiencing virological failure.

Study Overview

• Status: Completed
• Conditions: Human Immunodeficiency Virus; Treatment Efficacy; Monotherapy; Dolutegravir
• Intervention / Treatment: Drug: Dolutegravir

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Geneva, Switzerland, 1205
    • University Hospitals of Geneva, HIV unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infection;
• Patient included in the Swiss HIV Cohort Study (SHCS);
• ≥ 18 years of age;
• Virologically suppressed for at least 24 months on first line triple ART (changes for toxicity permitted) with at least 4 HIV-1 RNA measurements in plasma <50 copies/ml;
• No history of previous failure on ART;
• No documented antiretroviral drugs resistance;
• No co-infection with Hepatitis B or C virus;
• Effective contraception in women;
• Willing to provide CSF and semen samples;
• Written informed consent

Exclusion Criteria:

• HIV-2 infection;
• Renal dysfunction (creatinine clearance <50ml/min);
• aspartate transaminase or alanine aminotransferase >5x upper limit normal;
• Concomitant use of carbamazepine, oxcarbazepine, phenytoin, phenobarbital, St John's wort, rifampicin or metformin;
• Previous AIDS defining conditions or active malignancy in the past five years;
• Positive HIV viral load in CSF at baseline;
• Known or suspected non-compliance;
• Women who are pregnant or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dolutegravir monotherapy; 10 patients will be simplified to monotherapy of dolutegravir tablet 50mg once daily for 24 weeks	Drug: Dolutegravir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of patients without virological failure defined as plasma HIV-1 RNA ≥ 200 copies/ml on two consecutive measurements or positive HIV-1 RNA level in cerebrospinal fluid (CSF) at week 24 or before	week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24		week 24
Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure		week 24
Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24	Lumbar puncture is optional at baseline	week 24
Change from baseline CD4 cell count from baseline at week 24		week 24
Adherence to medication at weeks 4, 8, 12, 16, 20, 24	Number of participants with suboptimal adherence defined as more than 3 pills (10%) remaining from previous monthly visit OR missed more than one dose in a row OR missed dose more than once every two weeks	week 24
Lipidic profile changes from baseline at week 24		week 24
Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24		week 24
Change in bone mineral density from baseline to week 24	Number of patients with normal bone density, osteopenia or osteoporosis as defined by DXA scans results	week 24

Other Outcome Measures

Outcome Measure	Time Frame
Change in immune activation from baseline to week 24 measured by highly sensitive C-reactive protein (mg/l)	week 24
Change in immune activation from baseline to week 24 measured by cytokines (pg/ml)	week 24
Change in immune activation from baseline to week 24 measured by d-dimers (microg/l)	week 24

Collaborators and Investigators

• Sponsor: Calmy Alexandra
• Investigators: Principal Investigator: Delphine Sculier, MD, University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start: June 1, 2016
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): September 1, 2017

Study Registration Dates

• First Submitted: October 7, 2015
• First Submitted That Met QC Criteria: October 8, 2015
• First Posted (Estimate): October 9, 2015

Study Record Updates

• Last Update Posted (Actual): November 1, 2017
• Last Update Submitted That Met QC Criteria: October 31, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Anti-Retroviral Agents; Dolutegravir; HIV infection; Pharmacologic Actions; Therapeutic Uses; Integrase Inhibitors; HIV Integrase Inhibitors
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Dolutegravir
• Other Study ID Numbers: PRD-13-2015-I