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

Calmy Alexandra8 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Human Immunodeficiency Virus Dolutegravir Monotherapy Treatment Efficacy

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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

Time frame: week 24

Secondary Outcomes

Quantification of the HIV-1 DNA reservoir in peripheral blood monocyte cells at baseline and week 24

Time frame: week 24

Emergence of genotypic resistance in plasma HIV-1 RNA in case of virological failure

Time frame: week 24

Quantification HIV-1 RNA levels in the CSF and semen at baseline and week 24

Lumbar puncture is optional at baseline

Time frame: week 24

Change from baseline CD4 cell count from baseline at week 24

Time frame: 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

Time frame: week 24

Lipidic profile changes from baseline at week 24

Time frame: week 24

Body fat composition as measured by dual energy x-ray absorptiometry (DXA) scan at baseline and week 24

Time frame: 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

Time frame: week 24

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes