Clinical trial NCT02211690: The Tolerability of, and Adherence to, Dolutegravir With Co-formulated Tenofovir-emtricitabine for HIV Non-occupational Post-exposure Prophylaxis
Official title: The Tolerability of, and Adherence to, Dolutegravir With Co-formulated Tenofovir-emtricitabine for HIV Non-occupational Post-exposure Prophylaxis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Human Immunodeficiency Virus
Lead sponsor: St Vincent's Hospital, Sydney
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare Australia Pty. Ltd
First posted: 2014-08-07
Enrollment: 100
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: This study aims to describe the proportion of participants with non-occupational post-exposure prophylaxis (NPEP) failure, defined as NPEP non-completion (including loss to follow-up) at week 4 or primary HIV infection at week 4 or 12, excluding those participants who should and do cease study drug because:

1. The participant is found to be HIV-infected (study drugs will be ceased until the genotype of the infecting strain is determined)
2. The source is found to be HIV-uninfected

The primary study objectives are:

1. To describe on-drug adherence and regimen completion rates of 28 days of NPEP using dolutegravir (DTG) with co-formulated emtricitabine-tenofovir (FTC-TDF)
2. To describe the safety of 28 days of non-occupational post-exposure prophylaxis (NPEP) using dolutegravir with co-formulated emtricitabine-tenofovir

The study is a multi-site, prospective, open-label, non-randomized trial. One-hundred (100) eligible participants will receive dolutegravir (one tablet) with co-formulated emtricitabine-tenofovir, two tablets, once daily for 28 days based on one of the following exposures:

1. receptive anal intercourse with a source known to be HIV-infected; or
2. receptive anal intercourse with a source of unknown HIV status; or
3. insertive anal intercourse with a source known to be HIV-infected

There will be 7 study visits over a 12-week period. Follow-up post NPEP is for 8 weeks i.e. to week-12 post-exposure. Any participant who is intolerant of dolutegravir will be managed at the investigator's discretion.


Eligibility criteria: Inclusion Criteria:

1. Man who has sex with men
2. Age at least 18 years
3. Potential HIV exposure following:

   * receptive anal intercourse with a source known to be HIV-infected; or
   * receptive anal intercourse with a source of unknown HIV status; or
   * insertive anal intercourse with a source known to be HIV-infected
4. Able to provide written, informed consent
5. Able to commit to the study visits

Exclusion Criteria:

1. Non-sexual exposure
2. Exposure occurring during sex between a man and a woman
3. HIV infection diagnosed on baseline testing (antibody, Western blot, proviral DNA) including indeterminate serology consistent with possible primary HIV infection
4. Use of any medication contra-indicated with DTG, FTC or TDF
5. Use of any medication that effects the concentration of dolutegravir and / or concomitant drug including: oxcarbazepine, phenytoin, phenobarbital, carbamazepine, rifampicin, metformin or St. John's wort (St John's wort can be stopped for the 28-day period of NPEP).
6. History or presence of allergy to DTG, FTC, TDF or their components
7. Alanine aminotransferase (ALT) ≥5 times the upper limit of the reference range or ALT ≥3 times and bilirubin ≥1.5 times the upper limit of the reference range
8. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice) or known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
9. Severe hepatic impairment (Class C) as determined by Child-Pugh classification
10. Serum estimated Glomerular Filtration Rate (eGFR) \<60 mL/min/BSAc
11. Current therapy for hepatitis B infection
12. Serological evidence of chronic/active hepatitis B
13. Previous OPEP/NPEP containing DTG
14. A participant with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with the participant's participation for the full duration of the study
15. Unable to complete study procedures

Primary outcomes:
measure: Number of participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: twelve (12) weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Centre for Applied Medical Research
state: New South Wales
city: Sydney
country: Australia
facility: Sydney Sexual Health Centre
state: New South Wales
city: Sydney
country: Australia
facility: Clinic 16, Royal North Shore Hospital
state: New South Wales
city: Carlton
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Hospital
state: Victoria
Study officials:
References: