The Tolerability of, and Adherence to, Dolutegravir With Co-formulated Tenofovir-emtricitabine for HIV Non-occupational Post-exposure Prophylaxis

Study Overview
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Brief Summary
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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: The participant is found to be HIV-infected (study drugs will be ceased until the genotype of the infecting strain is determined) The source is found to be HIV-uninfected The primary study objectives are: To describe on-drug adherence and regimen completion rates of 28 days of NPEP using dolutegravir (DTG) with co-formulated emtricitabine-tenofovir (FTC-TDF) 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: 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 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.

Official Title
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The Tolerability of, and Adherence to, Dolutegravir With Co-formulated Tenofovir-emtricitabine for HIV Non-occupational Post-exposure Prophylaxis

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: dolutegravir 50 mg (one tablet daily)
* Drug: emtricitabine-tenofovir 300/200 mg (one tablet daily)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Man who has sex with men Age at least 18 years 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 Able to provide written, informed consent Able to commit to the study visits Exclusion Criteria: Non-sexual exposure Exposure occurring during sex between a man and a woman HIV infection diagnosed on baseline testing (antibody, Western blot, proviral DNA) including indeterminate serology consistent with possible primary HIV infection Use of any medication contra-indicated with DTG, FTC or TDF 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). History or presence of allergy to DTG, FTC, TDF or their components 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 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) Severe hepatic impairment (Class C) as determined by Child-Pugh classification Serum estimated Glomerular Filtration Rate (eGFR) <60 mL/min/BSAc Current therapy for hepatitis B infection Serological evidence of chronic/active hepatitis B Previous OPEP/NPEP containing DTG 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 Unable to complete study procedures

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: dolutegravir 50mg with co-formulated emtricitabine-tenofovir<br>One-hundred eligible participants will receive dolutegravir (1 x 50mg tablet) with co-formulated emtricitabine-tenofovir (1 tablet) once daily for 28 days | Drug: dolutegravir 50 mg (one tablet daily)<br> <br> Drug: emtricitabine-tenofovir 300/200 mg (one tablet daily)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse Events as a Measure of Safety and Tolerability |  | twelve (12) weeks |