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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Human Immunodeficiency Virus, Dolutegravir, Monotherapy, Treatment Efficacy

Intervention / Treatment
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* Drug: Dolutegravir


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dolutegravir, HIV infection, Anti-Retroviral Agents, HIV Integrase Inhibitors, Integrase Inhibitors, Pharmacologic Actions, Therapeutic Uses