Clinical trial NCT02572947: A Pilot Study of MONOtherapy of DOlutegravir in HIV-1 Virologically Suppressed Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Human Immunodeficiency Virus
Dolutegravir
Monotherapy
Treatment Efficacy
Keywords: Dolutegravir
HIV infection
Anti-Retroviral Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Pharmacologic Actions
Therapeutic Uses
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2015-10-09
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: week 24
Secondary outcomes:
measure: Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24
timeFrame: week 24
measure: Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure
timeFrame: week 24
measure: Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24
timeFrame: week 24
measure: Change from baseline CD4 cell count from baseline at week 24
timeFrame: week 24
measure: Adherence to medication at weeks 4, 8, 12, 16, 20, 24
timeFrame: week 24
measure: Lipidic profile changes from baseline at week 24
timeFrame: week 24
measure: Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24
timeFrame: week 24
measure: Change in bone mineral density from baseline to week 24
timeFrame: week 24
Other outcomes:
measure: Change in immune activation from baseline to week 24 measured by highly sensitive C-reactive protein (mg/l)
timeFrame: week 24
measure: Change in immune activation from baseline to week 24 measured by cytokines (pg/ml)
timeFrame: week 24
measure: Change in immune activation from baseline to week 24 measured by d-dimers (microg/l)
timeFrame: week 24
Locations:
city: Geneva
country: Switzerland
facility: University Hospitals of Geneva, HIV unit
Study officials:
affiliation: University Hospital, Geneva
name: Delphine Sculier, MD
role: PRINCIPAL_INVESTIGATOR
References: