Dolutegravir, Human Immunodeficiency Virus, Monotherapy, Treatment Efficacy
Conditions
Keywords
Dolutegravir, HIV infection, Anti-Retroviral Agents, HIV Integrase Inhibitors, Integrase Inhibitors, Pharmacologic Actions, Therapeutic Uses
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.
Interventions
DRUGDolutegravir
Sponsors
Calmy Alexandra
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| 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
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline CD4 cell count from baseline at week 24 | 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 | week 24 | Number of patients with normal bone density, osteopenia or osteoporosis as defined by DXA scans results |
| 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 | week 24 | Lumbar puncture is optional at baseline |
| Adherence to medication at weeks 4, 8, 12, 16, 20, 24 | week 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 |
Other
| Measure | Time frame |
|---|---|
| Change in immune activation from baseline to week 24 measured by d-dimers (microg/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 highly sensitive C-reactive protein (mg/l) | week 24 |
Countries
Switzerland
Outcome results
None listed