Metabolic Impact of Darunavir monotherapy vs Atripla in HIV patients
| ISRCTN | ISRCTN11504121 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11504121 |
| Secondary identifying numbers | JF-001 |
- Submission date
- 04/08/2010
- Registration date
- 12/11/2010
- Last edited
- 21/01/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Infections and Infestations
Plain English Summary
Background and study aims
The human immunodeficiency virus (HIV) is a type of virus known as a retrovirus. HIV attacks and weakens the immune system, making it more difficult for a sufferer to fight infections. It is a highly contagious disease, through bodily fluids such as blood, semen and vaginal fluids. There is currently no cure for HIV, but there are a range of drug treatments that can allow people who are HIV positive to lead a long and full life. Antiretroviral therapy (ART) is the standard treatment for HIV, where at least three different antiretroviral (ARV) drugs are given at the same time. This treatment is very effective at suppressing the virus and stopping the development of the disease. When a person has been on ART, the amount of HIV present in the blood (viral load) is reduced. After three to six months of treatment, the viral load should have fallen to undetectable levels (undetectable viral load). A commonly used ART is Atripla, which contains the three drugs efavirenz, emtricitabine, and tenofovir. Although this treatment can be very effective, it can cause long-term health problems, specifically problems with the bones and kidneys. A possible reason for this is the Atripla treatment could lead to reduced levels of different vitamins and minerals in the body, such as vitamin D and calcium, which can affect hormone levels. The aim of this study is to find out if treating HIV patients with the ARV’s Darunavir/Ritonavir only (single-drug therapy) is less toxic for bones and kidneys than standard ART.
Who can participate?
HIV positive adults, currently taking Atripla, who have had an undetectable viral load in the last 6 months.
What does the study involve?
Participants are randomly allocated to one of two groups. Those in the first group continue their Aripla therapy, which involves taking the Atripla tablets (which contain efavirenz, emtricitabine, and tenofovir) daily for the 48 week study. Those in the second group stop taking their Aripla and take darunavir 800mg/ritonavir 100mg every day for 48 weeks. At the start of the study and then every month until 48 weeks, participants provide blood and urine samples in order to test kidney function and biomarkers (chemical indicators) of bone health.
What are the possible benefits and risks of participating?
Not provided at time of registration.
Where is the study run from?
St. Thomas’ Hosptial (UK)
When is the study starting and how long is it expected to run for?
October 2010 to October 2013
Who is funding the study?
Tibotec (Janssen-Cilag Ltd) (UK)
Who is the main contact?
Dr Julie Fox
Contact information
Scientific
Harrison Wing
St. Thomas' Hospital
2nd Floor Lambeth Wing
Westminster Bridge Road
London
SE1 9RT
United Kingdom
Study information
| Study design | Multicentre open-label randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use contact details below to request a patient information sheet |
| Scientific title | The metabolic impact of darunavir/ritonavir maintenance monotherapy after successful viral suppression with standard Atripla in HIV-1 infected patients: an unblinded, multicentre, randomised controlled trial |
| Study acronym | MIDAs |
| Study hypothesis | This project aims to assess the potential long-term advantages of switching HIV patients from the standard therapy (Atripla) to a different regimen of treatment (darunavir 800 mg/ritonavir 100 mg) in terms of Vitamin D levels, calcium and phosphate homeostasis, renal (tubular) function, bone turnover and bone mineralisation and infection disease progression. On 07/05/2014 the anticipated start date was changed from 01/03/2012 to 01/10/2014. |
| Ethics approval(s) | Central London Research Ethics Committee 4, 04/08/2010 |
| Condition | HIV |
| Intervention | At baseline, patients will be randomised to receive either 1. Darunavir 800mg/ritonavir 100mg daily 2. Atripla® daily Study medication/HIV regimen will be dispensed at each study visit. All participants will have the opportunity to discuss continuing their study drug with their routine clinician at study end. |
| Intervention type | Other |
| Primary outcome measure | Change in 25(OH)Vitamin D |
| Secondary outcome measures | 1. Reduction in parathyroid hormone levels 2. Improvements in serum calcium, phosphate, alkaline phosphatase 3. Improvement in estimated glomerular filtration rate, albuminuria and proteinuria, tubular phosphate reabsorption and other markers of renal tubular dysfunction 4. Improvement in bone mineral density 5. Immune activation: change in immune activation (CD8+CD38+) 6. The proportion of participants without therapeutic failure (defined as two consecutive HIV-RNA values > 50 copies/ml) Outcomes will be measured throughout the study period though lab analysis will be carried out at end of the study. Samples will be blood/urine samples and for substudy, genital secretions. |
| Overall study start date | 01/10/2010 |
| Overall study end date | 01/10/2014 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Upper age limit | 65 Years |
| Sex | Both |
| Target number of participants | 70 |
| Participant inclusion criteria | 1. Between 18-65 Males and Females 2. Documented Positive HIV-antibody test and previous positive HIV-antibody test within three months of the start of the study 3. Plasma HIV RNA <50 copies/ml for at least six months on Atripla 4. Agree to NOT take vitamin D supplements for the duration of the study 5. Willing to use barrier contraception (condoms) for the duration of their participation in the study 6. Ability to give informed consent |
| Participant exclusion criteria | 1. Pregnancy or breast feeding 2. Patient unlikely to comply with protocol, and in particular adhere to therapeutic regimen 3. Patient likely to use narcotics during the study period 4. Hepatitis B co-infection (past or present) 5. Diabetes mellitus 6. Received vitamin D supplementation for more than one month within the previous 6 months 7. Current use or likely to require use of concomitant medication with known interactions with Darunavir or Ritonavir including rifampicin, amiodarone, flecainide, bupropion, clozapine, ergotamine, mexilitine, midazolam, pethidine, pimoziide, quinidine, sertindole, sildanefil, voriconazole, zolpidem, and St. Johns Wort would exclude a subject from the trial 8. Individuals experiencing side effects from their current regime will not be excluded from analysis |
| Recruitment start date | 01/10/2010 |
| Recruitment end date | 01/10/2014 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
2nd Floor Lambeth Wing
Westminster Bridge Road
London
SE1 9RT
United Kingdom
Sponsor information
Hospital/treatment centre
16th Floor, Tower Wing
Guy's Hospital
Great Maze Pond
London
SE1 9RT
England
United Kingdom
"ROR" |
https://ror.org/00j161312 |
|---|
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 02/01/2017 | 21/01/2019 | Yes | No |
| Results article | results of switching from Atripla to darunavir/ritonavir Monotherapy on neurocognition, quality of life, and sleep, | 01/12/2016 | 21/01/2019 | Yes | No |
| Results article | results of the effects on vitamin D, bone and the kidney when switching from fixed-dose tenofovir disoproxil fumarate/emtricitabine/efavirenz to darunavir/ritonavir monotherapy, | 01/01/2016 | 21/01/2019 | Yes | No |
Editorial Notes
21/01/2019: Publication reference added
03/04/2018:No publications found, verifying study status with principal investigator.
29/01/2016: No publications found, verifying study status with principal investigator.
