Tolerability and completion of Maraviroc compared to Kaletra® in combination with Truvada® for HIV Post Exposure Prophylaxis

ISRCTN	ISRCTN63350011
DOI	https://doi.org/10.1186/ISRCTN63350011
Protocol serial number	MMC001
Sponsor	Central and North West London NHS Foundation Trust (UK)
Funder	Pfizer (UK) ref: WS923309

Submission date: 22/07/2011
Registration date: 09/03/2012
Last edited: 13/02/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Post-exposure prophylaxis (PEP) involves taking anti-HIV medications as soon as possible after you may have been exposed to HIV to try to reduce the chance of becoming HIV positive. It is readily available for healthcare workers following occupational HIV exposure (during the performance of their job duties). The current Department of Health guidelines recommend treatment with combination of three drugs for 28 days, which should be started as soon as possible after the exposure, ideally within one hour. Post-exposure prophylaxis following non-occupational exposure to HIV (e.g., sexual contact, sharing of injection drug needles) is increasingly being provided and many countries including the UK have now developed guidelines for its use. However, studies also suggest that PEP is often poorly tolerated, with patients frequently reporting side effects and not completing their treatment. Identifying drug combinations likely to be better tolerated would therefore be extremely useful. The aim of this study is to determine if, when used in combination with tenofovir/emtricitabine, maraviroc is superior to lopinavir/ritonavir with respect to the proportion of patients who complete 28 days of PEP without developing adverse events.

Who can participate?
Patients aged 18 or over receiving PEP following occupational or non-occupational HIV exposure.

What does the study involve?
Participants are randomly allocated to either the control group or the experimental group. The control group receive 28 days’ treatment with tenofovir/emtricitabine (one tablet once daily) and lopinavir/ritonavir (two tablets twice daily). These drugs are the standard combination currently in use in most centers for PEP in the UK. The experimental group receive 28 days’ treatment with tenofovir/emtricitabine (one tablet once daily) and maraviroc (one tablet twice daily). Participants attend a follow-up visit 3 months after the last dose of medication.

What are the possible benefits and risks of participating?
Collecting blood samples could cause discomfort and may leave temporary bruises. Every effort will be made to minimise this. No additional blood samples will be required in this study beyond the routine care. Maraviroc and lopinavir/ritonavir PEP may cause side effects. The most common side effects are gastrointestinal (digestive) symptoms, but these are unlikely to require any action since the treatment is only given for short time. The study doctor will advise patients on the appropriate management of any side effects. Maraviroc has not ever been used as a part of HIV PEP so its effectiveness has not been documented, and any potential risks will be monitored and the study stopped if necessary.

Where is the study run from?
The Mortimer Market Centre, Camden Provider Services, London
The Claude Nicol Unit, Brighton and Sussex University Hospitals NHS Trust, Brighton
The John Hunter Clinic, Chelsea and Westminster NHS Foundation Trust, London
The Lydia Clinic, St Thomas’ Hospital, London

When is the study starting and how long is it expected to run for?
October 2011 to June 2013.

Who is funding the study?
Global Investigator Initiated Research Group, Pfizer

Who is the main contact?
Dr Paul Benn

Contact information

Dr Paul Benn
Scientific

Mortimer Market Centre
Off Capper Street
London
WCE 6JB
United Kingdom

Study information

Primary study design	Interventional
Study design	Multicentre open-label randomised study
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Randomised controlled trial of the tolerability and completion of Maraviroc compared to Kaletra® in combination with Truvada® for HIV Post Exposure Prophylaxis
Study acronym	MiPEP
Study objectives	This trial aims to determine whether maraviroc-based combination antiretroviral therapy (ART) is superior to a lopinavir (LPV) based combination, in terms of the proportion of patients who complete a full post exposure prophylaxis (PEP) course, and to compare clinical events, safety and toxicity between the two groups.
Ethics approval(s)	1 .NRES Committee London - Riverside ref: 11/LO/1333 2. NHS Brighton and Hove
Health condition(s) or problem(s) studied	HIV
Intervention	Control arm: Patients randomised to the control arm will receive 28 days treatment with Truvada® (tenofovir disoproxil - as fumarate, 245 mg, emtricitabine 200 mg), one tablet once daily in addition to Kaletra® (lopinavir 200 mg, ritonavir 50 mg), two tablets twice daily. These drugs are the standard combination currently in use in most centres for PEP in the UK. Experimental arm: Patients randomised to the experimental arm will receive 28 days treatment with Truvada® (tenofovir disoproxil -as fumarate- 245 mg, emtricitabine 200 mg), one tablet once daily in addition to maraviroc (300 mg), one tablet twice daily.
Intervention type	Drug
Phase	Phase IV
Drug / device / biological / vaccine name(s)	Tenofovir/emtricitabine, maraviroc, lopinavir/ritonavir
Primary outcome measure(s)	1. Composite end point of completion of 28 days of allocated PEP regimen without Grade 3 or 4 clinical or laboratory adverse events 2. Division of AIDS table for Grading the severity of Adult and Paediatric Adverse Events
Key secondary outcome measure(s)	1. Completion rates of 28 days of allocated PEP regimen 2. Rates of Grade 1, 2, 3 or 4 clinical adverse events 3. Rates of Grade 1, 2, 3 or 4 laboratory anormalities 4. Rates and causes of regimen modification or discontinuation 5. Number of missed doses of Truvada® over 28 day course of PEP 6. Number of missed doses of Kaletra®or maraviroc over 28 day course of PEP 7. Number of doses of antidiarrhoeal medication taken 8. Number of doses of antiemetic taken 9. Number of days absent from work or college (not including days attending for clinic visits) 10. Number of clinic visits required 11. Rates of HIV seroconversion at month 4 after exposure 12. Proportion of individuals reporting unprotected anal/vaginal intercourse in 12.1. The three months preceeding PEP 12.2. While receiving PEP and 12.3. In the three months post completion of PEP with a potentially sero-discordant partner 13. Number of sexual partners in 13.1. The three month period preceeding PEP 13.2. While receiving PEP 13.3. The three month period following PEP 14. Rates of sexually transmitted infections [gonorrhoea, chlamydia, Lymphogranuloma venereum (LGV), syphilis, hepatitis B and C]
Completion date	01/06/2013

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	All
Target sample size at registration	280
Key inclusion criteria	1. 18 years old or older 2. A patient attending one of four genitourinary medicine clinics and for whom PEP is considered appropriate by the clinician according to current guidelines including following occupational or non occupational exposure 3. Willing to provide written informed consent
Key exclusion criteria	1. The baseline human immunodeficiency virus (HIV) test is reactive or positive 2. Currently receiving medication which would reduce the effectiveness of Kaletra® / maraviroc 3. Currently receiving medication where the interaction would result in a dangerously high level of the concomitant drug 4. Pregnant or trying to become pregnant at the time of trial entry 5. The source is known to have multi-drug resistant HIV and therefore more likely to have CXCR 4 tropic virus 6. History of active substance abuse or psychiatric illness that, in the opinion of the investigator, would preclude compliance with the protocol, dosing schedule or assessments 7. Any other active clinically significant condition, or findings during screening medical history or examination, or abnormality on screening laboratory blood tests that would, in the opinion of the investigator, compromise the patients safety or outcome in the trial
Date of first enrolment	03/12/2011
Date of final enrolment	31/05/2013

Locations

Countries of recruitment

United Kingdom

Study participating centres

Mortimer Market Centre

Camden Provider Services
London
WCE 6JB
United Kingdom

The Claude Nicol Unit

Brighton and Sussex University Hospitals NHS Trust
Brighton
-
United Kingdom

The John Hunter Clinic

Chelsea and Westminster NHS Foundation Trust
London
-
United Kingdom

The Lydia Clinic

St Thomas’ Hospital
London
-
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2017		Yes	No
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

13/02/2018: pub ref added