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

Human Immunodeficiency Virus Clinical Trial

— MONODO  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02572947
• Other study ID #: PRD-13-2015-I
• Status: Completed
• Phase: Phase 2
• First received: October 7, 2015
• Last updated: October 31, 2017
• Start date: June 2016
• Est. completion date: September 2017

Study information

• Verified date: October 2017
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: September 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Dolutegravir
• HIV Infections
• Human Immunodeficiency Virus
• Immunologic Deficiency Syndromes
• Monotherapy
• Treatment Efficacy

Intervention

Drug:
• Dolutegravir

Locations

Country	Name	City	State
Switzerland	University Hospitals of Geneva, HIV unit	Geneva

Sponsors (1)

Lead Sponsor	Collaborator
Calmy Alexandra

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in immune activation from baseline to week 24 measured by highly sensitive C-reactive protein (mg/l)		week 24
Other	Change in immune activation from baseline to week 24 measured by cytokines (pg/ml)		week 24
Other	Change in immune activation from baseline to week 24 measured by d-dimers (microg/l)		week 24
Primary	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	Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24		week 24
Secondary	Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure		week 24
Secondary	Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24	Lumbar puncture is optional at baseline	week 24
Secondary	Change from baseline CD4 cell count from baseline at week 24		week 24
Secondary	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
Secondary	Lipidic profile changes from baseline at week 24		week 24
Secondary	Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24		week 24
Secondary	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