Validation of a Urine Assay to Measure Tenofovir Levels in Patients Taking Tenofovir Alafenamide
| Status: | Completed |
|---|---|
| Conditions: | HIV / AIDS |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 6/29/2018 |
| Start Date: | November 16, 2017 |
| End Date: | May 1, 2018 |
Pre-exposure prophylaxis (PrEP) with Truvada™ (tenofovir/emtricitabine), in which an
HIV-uninfected individual at high risk for contracting HIV takes antiretroviral medications
(one pill daily) to maintain blood and genital drug levels sufficient to prevent HIV-1
acquisition, has been validated in several large international trials that have included men
who have sex with men and transgender women, heterosexual men and women, and people who use
injection drugs, as a potential HIV-1 prevention strategy. HIV prevention interventions such
as this, if adequately disseminated and implemented broadly, may help to curb new HIV
infections, reduce HIV-associated morbidity and mortality, and reduce health disparities in
HIV rates among the most at-risk individuals. Assuring adherence to a daily dose of PrEP is
critical for effective protection against HIV infection. A urine-based test to measure PrEP
medication levels in the body represents a non-invasive technique to assess adherence and
ultimately improve PrEP's protective ability.
TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as
effective as Truvada™. This study is testing whether a urine test can detect this medication
in urine.
HIV-uninfected individual at high risk for contracting HIV takes antiretroviral medications
(one pill daily) to maintain blood and genital drug levels sufficient to prevent HIV-1
acquisition, has been validated in several large international trials that have included men
who have sex with men and transgender women, heterosexual men and women, and people who use
injection drugs, as a potential HIV-1 prevention strategy. HIV prevention interventions such
as this, if adequately disseminated and implemented broadly, may help to curb new HIV
infections, reduce HIV-associated morbidity and mortality, and reduce health disparities in
HIV rates among the most at-risk individuals. Assuring adherence to a daily dose of PrEP is
critical for effective protection against HIV infection. A urine-based test to measure PrEP
medication levels in the body represents a non-invasive technique to assess adherence and
ultimately improve PrEP's protective ability.
TAF/FTC (Descovy™) is a new medication under study for HIV prevention to see if it is as
effective as Truvada™. This study is testing whether a urine test can detect this medication
in urine.
Primary Objectives:
1a) To determine how long TFV is excreted in the urine in patients at steady state of
TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct
observation to ensure adherence. Morning urine and plasma samples will be collected starting
the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10
days of sample collection). This will allow for the assessment of the length of time TFV can
be measured in the urine after last dose is taken (the "lookback" period) in the context of
consistent adherence, as well as to determine how many days a patient has been off drug if a
urine specimen has no detectable TFV. A correction analysis similar to that below will also
be assessed in this cohort.
1b) To determine how long TFV is excreted in the urine in patients who have taken one dose of
TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to
ensure adherence. Morning urine and plasma samples will be collected starting the day the
dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample
collection). This will allow for the assessment of the length of time TFV can be measured in
the urine after last dose is taken (the "lookback" period) in the context of inconsistent or
intermittent (1 day only) adherence, as well as to determine how many days a patient has been
off drug if a urine specimen has no detectable TFV. Investigators will also examine the
correct urine TFV values for inter-subject variability by assessing which measure (specific
gravity, urine creatinine, pH) will maximize the correlation between urine TFV levels and an
ideal line of elimination.
Secondary Objective:
To determine the expected urine tenofovir levels in a population of HIV-positive patients on
TAF-based regimens. A cross-sectional analysis of ten HIV-positive patients with undetectable
viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine and
plasma samples will be collected at one time point to determine urine TFV concentration in
the setting of steady state dosing in HIV patients with presumably very good adherence to
medication, and compared to a historical cohort of patients on TDF-based regimens.
1a) To determine how long TFV is excreted in the urine in patients at steady state of
TAF/FTC. Ten healthy subjects will be given seven daily doses of TAF/FTC under direct
observation to ensure adherence. Morning urine and plasma samples will be collected starting
the day the last is given (1 hour later) and every day thereafter for 9 days (total of 10
days of sample collection). This will allow for the assessment of the length of time TFV can
be measured in the urine after last dose is taken (the "lookback" period) in the context of
consistent adherence, as well as to determine how many days a patient has been off drug if a
urine specimen has no detectable TFV. A correction analysis similar to that below will also
be assessed in this cohort.
1b) To determine how long TFV is excreted in the urine in patients who have taken one dose of
TAF/FTC. Ten healthy subjects will be given one dose of TAF/FTC under direct observation to
ensure adherence. Morning urine and plasma samples will be collected starting the day the
dose is given (1 hour later) and every day thereafter for 6 days (total of 7 days of sample
collection). This will allow for the assessment of the length of time TFV can be measured in
the urine after last dose is taken (the "lookback" period) in the context of inconsistent or
intermittent (1 day only) adherence, as well as to determine how many days a patient has been
off drug if a urine specimen has no detectable TFV. Investigators will also examine the
correct urine TFV values for inter-subject variability by assessing which measure (specific
gravity, urine creatinine, pH) will maximize the correlation between urine TFV levels and an
ideal line of elimination.
Secondary Objective:
To determine the expected urine tenofovir levels in a population of HIV-positive patients on
TAF-based regimens. A cross-sectional analysis of ten HIV-positive patients with undetectable
viral loads on a TAF-based single tablet HIV regimen will be conducted. Morning urine and
plasma samples will be collected at one time point to determine urine TFV concentration in
the setting of steady state dosing in HIV patients with presumably very good adherence to
medication, and compared to a historical cohort of patients on TDF-based regimens.
Cohort 1(a & b) Inclusion Criteria:
- Age 18 or older at the time of signed informed consent
- Not currently taking commercial Truvada for PrEP or any other investigational, oral
medication for the purpose of HIV PrEP
- Willing and able to independently provide written informed consent
- Tests HIV negative at time of screening using rapid HIV antibody test or serum
antibody/antigen 4th generation HIV test
Cohort 1(a & b) Exclusion Criteria:
- Evidence of acute or chronic hepatitis B infection at the time of screening
- Other clinically significant acute or chronic medical condition, including severe
infections requiring treatment such as tuberculosis, as determined by the study
investigator
- Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of
screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) /
(72 x serum creatinine)
- History of bone fractures not explained by trauma
- Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS
grading system
- Known allergy/sensitivity to the study drug or its components
- Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
- Any other clinical condition or prior therapy that, in the opinion of the Principal
Investigator, would make the subject unsuitable for the study or unable to comply with
the dosing requirements
Cohort 2 Inclusion Criteria:
- Age 18 or older at the time of signed informed consent
- Willing and able to independently provide written informed consent
- Last viral load < 20 copies/mL within the last four weeks of screening
- Must be on combination antiretroviral therapy that includes TAF/FTC for at least 6
months
- Undetectable viral load, as defined by < 50 copies/ml, for at least 6 months
Cohort 2 Exclusion Criteria:
- Other clinically significant acute or chronic medical condition, including severe
infections requiring treatment such as tuberculosis, as determined by the study
investigator
- Evidence of renal dysfunction (Creatinine Clearance < 30 ml/min) at the time of
screening; Use Cockroft-Gault equation: GFR = (140-Age in years) x (Weight in kg) /
(72 x serum creatinine)
- Grade 3 laboratory abnormality on screening tests/assessments as defined by the DAIDS
grading system
- Experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
- Any other clinical condition or prior therapy that, in the opinion of the Principal
Investigator, would make the subject unsuitable for the study or unable to comply with
the dosing requirements
We found this trial at
1
site
Philadelphia, Pennsylvania 19107
Principal Investigator: Helen Koenig, MD
Phone: 215-985-4448
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