Development of a Urine-Based Point-of-Care Test for Adherence to Antiretroviral Drugs

  • STATUS
    Recruiting
  • End date
    Dec 31, 2022
  • participants needed
    30
  • sponsor
    Rhonda Brand
Updated on 25 January 2021
antiretroviral agents
tenofovir
emtricitabine
hepatitis
sexually transmitted disease
fumarate
emtricitabine/tenofovir
reverse transcriptase inhibitor
dolutegravir
lamivudine
HIV Vaccine
drug test
venereal disease

Summary

This is a single-center, open label study to identify adherence levels of commonly prescribed FDA-approved antiretroviral agents by tracking the decline of drug concentrations in plasma, urine and saliva following abrupt drug cessation in HIV-negative adults. Results from this study may provide support for development of a point of care urine testing device to monitor drug adherence.

Description

Poor adherence to antiretroviral (ARV) therapy and HIV pre-exposure prophylaxis (PrEP) incurs costs for patients, health systems, and society. Non-adherence to ARV precedes viral breakthrough and offers opportunities for health-care professionals to intervene. There is a need for accurate, affordable, rapid, and objective monitoring of adherence to be deployed as a companion diagnostic to ARV therapy. Self-reported questionnaires, physician and nurse adherence consistently over-estimate adherence, and pill counts, and pharmacy returns do not yield sufficient precision for individual patients. Therapeutic drug monitoring (TDM) has the advantage tracking medication intake, but sample storage and processing requirements, turnaround times and relatively high cost preclude their widespread deployment. There is a real clinical need for point-of-care adherence testing, which will have high clinical utility by allowing targeting of adherence support and monitoring, better medication review, and integration with community support.

Since the clinical utility of any point-of-care test (POCT) will be its negative predictive value, this trial has been designed as a 'tail' study to track the decline of drug concentrations in plasma, urine and saliva following abrupt drug cessation. Such a study will require dosing to healthy participants who are dosed to steady-state prior to treatment discontinuation.

Serial measurement of drug concentrations in plasma, saliva and urine will be used to develop population-based models which adequately describe the kinetics of elimination and population variability in drug exposure. These models will be used to simulate population drug exposures from which target cut-offs are derived for development of a POCT device.

Approximately thirty healthy, HIV-uninfected participants will be enrolled and equally assigned to one of two ARV dosing arms using a permuted block design randomization scheme.

ARM 1: dolutegravir 50 mg + emtricitabine 200 mg/tenofovir alafenamide 25 mg once daily for 15 days

ARM 2: dolutegravir 50 mg + tenofovir disoproxil fumarate 300 mg + lamivudine 300 mg once daily for 15 days

To assess ARV pharmacokinetics during dosing and over 14 days following ARV cessation, blood, urine, and saliva samples will be collected at Days 1, 2, 8, 15, 16, 17, 18, 19, 22 and 29.

Details
Condition HIV, HIV positive, HIV infection, AIDS Vaccines, Noncompliance with medication regimen, HIV (Pediatric), HIV Infections, human immunodeficiency virus, hiv disease, HIV Vaccine, hiv vaccines
Treatment dolutegravir oral tablet 50mg, emtricitabine/tenofovir alafenamide oral tablet 200mg/25mg, tenofovir disoproxil fumarate oral tablet 300mg, lamivudine oral tablet 300mg
Clinical Study IdentifierNCT04302896
SponsorRhonda Brand
Last Modified on25 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

At least 18 years of age at screening, verified per site standard operating procedure (SOP)
Not pregnant or breastfeeding
Availability to return for all study visits, barring unforeseen circumstances
Willing and able to
communicate in English
provide written informed consent to take part in the study
provide adequate locator information, as defined in site SOP
follow the assigned dosing protocol and maintain an accurate dosing log
Must agree not to participate in other concurrent interventional and/or drug trials
Understands and agrees to local sexually transmitted infections (STI) reporting requirements
HIV-1 seronegative at screening
Must be in general good health in the opinion of the investigator
For female participants of reproductive potential: Using an effective method of contraception and intending to continue use of an effective method for the duration of study participation and for 8 weeks after the last dose of study drug. Acceptable methods include
hormonal methods
IUD (intrauterine device)
sterilization of participant or partner

Exclusion Criteria

Participant reports any of the following at Screening
Has plans to relocate away from the study site area during the period of study participation
Pregnant, less than 3 months post-partum, or lactating
Intends to become pregnant during the period of study participation
History of adverse reaction to study drugs
History of osteoporosis or osteopenia
PrEP (pre-exposure prophylaxis) or (PEP) post-exposure prophylaxis for HIV exposure within 3 months - prior to screening
Participating in another research study involving drugs or medical devices within 3 months or 5 half-lives (if known) prior to enrollment
History of gastric bypass
History of inflammatory bowel disease
Currently taking or anticipation of taking any medications on list of prohibited medications as specified in section 4.10
Unwilling or unable to comply with study procedures, medications and visits
Allergies to dyes, excipients and components of drugs
Condomless insertive or receptive anal intercourse with more than one partner in the past six months
Known HIV-positive sexual partner within the last 6 months
History of STI in the last 3 months
Has any of the following laboratory abnormalities at Screening
Note: Grade is per Version 2.1 of the Division of AIDS (DAIDS) Toxicity Table
Hemoglobin Grade 1 or higher
Platelet count Grade 1 or higher
White blood cell count Grade 2 or higher
Calculated creatinine clearance 70 mL/minute using the Cockcroft-Gault equation
Grade 2 or higher ALT and/or AST (i.e., 2.5x the site laboratory upper limit of normal [ULN])
Total bilirubin Grade 3 or higher
Positive for Hepatitis B surface antigen (HBsAg)
Confirmed positive for Hepatitis C antibody (HCV Ab)
Has any other condition that, in the opinion of the Principal Investigator or designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving study objectives
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