A Phase 1/2 interventional study of Switch to E/C/FTC/TAF daily in HIV/AIDS, Antiviral Toxicity and Antiviral Drug Adverse Reaction, sponsored by University of California, Los Angeles. Completed at 1 site in United States. Open to participants aged 18 Years to 80 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-05-10.
Sponsored by University of California, Los Angeles · Phase 1/2, Interventional, and Basic science
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Among 31 studies in Acquired Immunodeficiency Syndrome by University of California, Los Angeles — 3 open to participants now, 7 under way, none of them phase 3. Acquired Immunodeficiency Syndrome · University of California, Los Angeles.
Among the 31 studies in Acquired Immunodeficiency Syndrome by University of California, Los Angeles, this one is the 23rd largest by enrollment of the 25 interventional ones that give a count, is one of 4 that started in 2019, is the only one in phase 1/2, and was the 15th registered.
3,037 studies on the registry are indexed under Acquired Immunodeficiency Syndrome; 307 are open to participants now.
Browse Acquired Immunodeficiency Syndrome studies →3 of the 31 studies in Acquired Immunodeficiency Syndrome by University of California, Los Angeles are open now, in 2 countries. Recruiting first, the newest first:
University of California, Los Angeles · Sites in Vietnam
Ages 16+ · Men only
University of California, Los Angeles · Sites in United States
Ages 18+
University of California, Los Angeles · Sites in United States
Ages 21–40 · Women only
By country, each count listing its studies:
Of the 198 Acquired Immunodeficiency Syndrome studies recruiting now, 118 (60%) set no upper age limit and 67 (34%) stop at 75 or younger; 43 take children under 18; 68 take healthy volunteers.
This study: 18 Years to 80 Years · all sexes · healthy volunteers too.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
31 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 1 · Phase 2 4 · Phase 3 2 · Phase 4 1
First in 2008; this study’s year is marked. 4 started in 2019.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 26 is below the median of 96 across 2,252 interventional studies indexed under Acquired Immunodeficiency Syndrome.
Median enrollment 220 across the 25 interventional studies, 216 across the 6 observational. Of the 24 that completed or were terminated, 6 (25%) have results posted.
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University of California, Los Angeles is the lead sponsor of 1,170 studies on the registry; 195 are open to participants now.
Of its 95 completed or terminated interventional studies of FDA-regulated products, 70 (74%) have results posted.
1 of the studies in Acquired Immunodeficiency Syndrome by University of California, Los Angeles that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06480578University of California, Los AngelesAn Integrated Intervention Using a Pill Ingestible Sensor System | 2027-07-01 |
Add it to your calendar (.ics) → With an account.
Among the 31 studies in Acquired Immunodeficiency Syndrome by University of California, Los Angeles, from their registry updates:
Nothing recorded among them since 2026-09-25.
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Increased comorbidities such as cardiovascular disease (CVD), are emerging problems in HIV infection but the mechanisms are unclear. Understanding how antiretrovirals can minimize morbidity in treated HIV infection is a research priority. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are included in all HIV treatment regimens. Tenofovir (TFV) disoproxil fumarate (TDF) has been associated with an increased risk of nephrotoxicity and bone disease compared with other NRTIs. Tenofovir alafenamide (TAF) is an oral prodrug of TFV, but is more stable in plasma as compared with TDF and lower plasma levels of TFV are thought to lead to the favorable safety profile of TAF. Mitochondrial dysfunction has a key role in HIV pathogenesis and may be the common denominator that drives pathogenesis of several comorbidities. Despite the better safety profile of newer (such as TDF) compared to older NRTIs, there are concerns for the potential for longer term toxicity of NRTIs since the exact cellular effects of NRTIs remain unclear. It is unknown whether a four-fold increase in intracellular drug levels seen in peripheral blood mononuclear cells (PBMCs) with TAF may increase toxicity in mitochondria. Better understanding of these effects could provide insights into mechanisms of HIV pathogenesis and selection of NRTIs that improve morbidity in chronic HIV infection.
Hypothesis: Despite higher intracellular levels, TAF has minimal mitochondrial toxicity compared to TDF in vivo. This research will explore the relative mitochondrial toxicity of newer NRTIs (TAF, TDF) as a possible mechanism for differential NTRI-related toxicities. These data will allow selection of NRTIs that may improve morbidity in chronic treated HIV infection. Towards this aim, the investigators will use a robust experimental approach to study NRTI-related mitochondrial dysfunction using novel methods, human cell lines and PBMC. Our specific aims are: Aim 1: To evaluate the relative in vitro effects of TAF and TDF compared to an older NRTI (ddC) on 5 independent measures of mitochondrial function in the human cell line HepG2 and PBMC. Aim 2: To explore in vivo whether there is increased mitochondrial dysfunction with the use of TAF vs. TDF in chronic treated HIV infection. The investigators anticipate that the proposed experimental approach will set the basis for future large scale studies to directly compare subtle potential mitochondrial toxicities of newer NRTIs in large HIV cohorts.
Increased comorbidities such as cardiovascular disease (CVD), bone and kidney disease are emerging problems in HIV infection but the mechanisms are unclear. Understanding how antiretrovirals can minimize morbidity in treated HIV infection is a research priority. Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) are included in all HIV treatment regimens. Tenofovir (TFV) disoproxil fumarate (TDF) has been associated with an increased risk of nephrotoxicity and bone disease compared with other NRTIs. Tenofovir alafenamide (TAF) is an oral prodrug of TFV, but is much more stable in plasma as compared with TDF and markedly lower plasma levels of TFV are thought to lead to the favorable safety profile of TAF. Mitochondrial dysfunction has a key role in HIV pathogenesis and may be the common denominator that drives pathogenesis of several comorbidities. Despite the better safety profile of newer (such as TDF) compared to older NRTIs, there remain concerns for the potential for longer term toxicity of the current NRTIs especially since the exact cellular effects of NRTIs remain unclear. It is unknown whether a four-fold increase in intracellular drug levels seen in peripheral blood mononuclear cells (PBMCs) with TAF may increase toxicity in mitochondria. Better understanding of these effects could provide insights into mechanisms of HIV pathogenesis and selection of NRTIs that improve morbidity in chronic HIV infection.
Hypothesis: Despite higher intracellular levels, TAF has minimal/no overall mitochondrial toxicity compared to TDF in vivo. The investigators anticipate that the preliminary data and the proposed experimental approach will set the basis for future large scale studies to directly compare subtle potential mitochondrial toxicities of newer NRTIs in large HIV cohorts.
Primary Objective: This research application will explore the relative mitochondrial toxicity of newer NRTIs (TAF, TDF) as a possible mechanism for differential NTRI-related toxicities. These data will allow selection of NRTIs that may improve morbidity in chronic treated HIV infection, given the known possible role of mitochondrial dysfunction in pathogenesis of HIV-related comorbidities. Towards this aim, the investigators will use a robust experimental approach to study NRTI-related mitochondrial dysfunction using novel methods, human cell lines and PBMC. The specific aims of this project are: Aim 1: To evaluate the relative in vitro effects of TAF and TDF compared to an older NRTI (ddC) on 5 independent measures of mitochondrial function in the human cell line HepG2 and PBMC. Hypothesis: Despite higher intracellular levels, TAF has minimal/no overall mitochondrial toxicity compared to TDF in both the HepG2 line and PBMC. ddC will be used as a positive control for NRTI-induced mitochondrial dysfunction. Aim 2: To explore in vivo whether there is increased mitochondrial dysfunction with the use of TAF vs. TDF in chronic treated HIV infection. The overall goal of this proposal is to determine the in vitro and in vivo effects of TAF on mitochondria.
Treatment regimen: Healthy HIV-uninfected > 18 years old with no known comorbidities including metabolic disease will be recruited for PBMC isolation for the in vitro studies described in Aim 1 (n=30). For Aim 1, cells will be exposed to 10 μM (and other dose that will be determined after discussions with Gilead) NRTIs (TDF, TAF, ddC) for up to 14 days of treatment. To evaluate the relative mitochondrial toxicity of TDF vs. TAF in vivo (Aim 2), an open-label switch study will be conducted in virologically-suppressed, HIV-1 positive participants. The switch regimen will be Stribild® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir disoproxil fumarate 300 mg; E/C/F/TDF) to Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg; E/C/F/TAF). For inclusion and exclusion criteria see respective sections.
Primary Endpoint: Overall, the above in vitro and in vivo measurements of mitochondrial function before and after TAF and TDF will test the hypotheses that newer NRTIs have minimal overall mitochondrial toxicity in humans. From all the measures of mitochondrial function, cellular oxygen consumption (COC; as determined by Seahorse technology) will be considered the "gold standard" given it is a measure of the most important mitochondrial function (oxidative phosphorylation) that relates to clinical outcome. Given the uncertainty of what measure of mitochondrial function can best predict NRTI-induced mitochondrial toxicity, comparison of relative fold induction of mitochondrial dysfunction in PBMC vs. HepG2 cells in response to a specific concentration of a known NRTI inducer of mitochondrial dysfunction (ddC) will be used to guide analysis. The baseline measurement will be used to control for confounders of NRTI-related mitochondrial dysfunction (each person will serve as his/her own control) and results will be expressed as relative-fold change compared to baseline. In addition, using similar approach, Aim 2 will explore whether switch from TDF to a TAF-based regimen will induce any changes in measures of mitochondrial function. This approach ensures that any changes in the mitochondrial function at 6 and/or 12 months will be secondary only to the NRTI switch.
Secondary Endpoints: It is accepted that two independent measures of mitochondrial function can more reliably predict mitochondrial dysfunction compared to each one of the measures separately. The investigators will define NRTI-induced mitochondrial toxicity as significant change in any of other major measures of mitochondrial toxicity [reduction in membrane potential (Δψm), increase in mitochondrial reactive oxygen species (mito-ROS), decrease in the amount of mitochondrial DNA (mtDNA), abnormal mitochondrial dynamics (increase fragmentation of mitochondria)). Finally, other exploratory secondary endpoints (based on available left-over resources) will be measurement of intracellular levels of TAF metabolites. Flow cytometry and live cell imaging will be determined as needed.
The investigators will define NRTI-induced mitochondrial toxicity as significant change in any of the measures of mitochondrial toxicity (COC, Δψm, mito-ROS, mtDNA, mitochondrial dynamics). The baseline measurement will be used to control for confounders of NRTI-related mitochondrial dysfunction (each person will serve as his/her own control) and results will be expressed as relative-fold change compared to baseline. In addition, using similar approach, Aim 2 will explore whether switch from TDF to a TAF-based regimen will induce any changes in measures of mitochondrial function. This approach ensures that any changes in the mitochondrial function at 6 and/or 12 months will be secondary only to the NRTI switch.
Since each donor will contribute samples to all experimental groups (baseline, follow up measurement), paired t-test, linear mixed effects model and nonparametric test (as needed) will be used to compare expression measures between groups adjusting for donor effects (age, sex, race.
The results from this research will yield useful information on NRTI-related overall mitochondrial dysfunction that can further be validated in large studies with data on clinical outcomes.
Inclusion Criteria:
All HIV negative participants must meet the following criteria:
Willing to abstain from insertion of anything (drug, enema, penis or sex toy) in rectum for 12 hours before and 72 hours after each flexible sigmoidoscopy
In addition to the criteria listed above, female participants must meet the following criteria
HIV participant inclusion criteria
Specific enrollment inclusion criteria include:
Exclusion Criteria:
Participants who meet any of the following criteria at screening will be excluded from the study:
Positive STI at screening (urine NAAT)
o Participants will be allowed one re-screening visit after appropriate STI treatment
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Intervention: Participants will be asked to switch antiretrovirals (ART) for a period up to 12 months and mitochondrial physiology will be assessed using a variety of assays. The new ART will be 1. If the participant is on an ART other than Elvitegravir (ELV)/cobicistat CO)/emtricitabine (FTC)/tenofovir (TDF)\] (E/C/FTC/TDF) then the participant will be asked to switch to E/C/FTC/TDF for up to 6 months. This will allow for future switch (after these 6 months) from E/C/FTC/TDF 1 tablet once daily to E/C/FTC/ tenofovir alafenamide (TAF) 1 tablet once daily for a period of 12 months. 2. If the participant is on E/C/FTC/TDF 1 tablet once daily then the participant will be asked to switch from /C/FTC/TDF 1 tablet once daily to /C/FTC/TAF 1 tablet once daily for a period of 12 months.
Drug: Switch to E/C/FTC/TAF daily
If the participant is on an antiretroviral regimen other than Elvitegravir (ELV)/cobicistat CO)/emtricitabine (FTC)/tenofovir (TDF)\] (E/C/FTC/TDF) then the participant will be asked to switch to E/C/FTC/TDF for up to 6 months. This will allow for future switch (after these 6 months) from E/C/FTC/TDF 1 tablet once daily to elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/FTC/TAF) 1 tablet once daily for a period of 12 months. b) If the participant is on E/C/FTC/TDF 1 tablet once daily then the participant will be asked to switch from /C/FTC/TDF 1 tablet once daily to /C/FTC/TAF 1 tablet once daily for a period of 12 months.
Also known as: E/C/FTC/TDF 1 tablet once daily
Change in Mitochondrial Function [Cellular Oxygen Consumption (COC)] Over 12 Months After Switch of Antiretrovirals.
Change in mitochondrial function \[abnormal mitochondrial dynamics \[(cellular oxygen consumption (COC)\] over 12 months after switch of antiretrovirals.
Time frame: 12 month visit after switch
| Milestone | TAF Based ART | TDF Based ART |
|---|---|---|
| Started | 15 | 11 |
| Completed | 15 | 11 |
| Not completed | 0 | 0 |
Change in mitochondrial function \[abnormal mitochondrial dynamics \[(cellular oxygen consumption (COC)\] over 12 months after switch of antiretrovirals.
| pmoles O2/min | TAF Based ART | TDF Based ART |
|---|---|---|
| Change in Mitochondrial Function [Cellular Oxygen Consumption (COC)] Over 12 Months After Switch of Antiretrovirals. | 50 (42 to 58) | 70 (65 to 72) |
Collected over Up to 9 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| TAF Based ART | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| TDF Based ART | 0/11 (0%) | 0/11 (0%) | 0/11 (0%) |
Patients on TAF based vs TDF based ART
| Age, Categorical(Participants) | TAF Based ART | TDF Based ART | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 15 | 11 | 26 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | TAF Based ART | TDF Based ART | Total |
|---|---|---|---|
| Female | 0 | 0 | 0 |
| Male | 15 | 11 | 26 |
| Race (NIH/OMB)(Participants) | TAF Based ART | TDF Based ART | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 2 | 2 | 4 |
| White | 13 | 9 | 22 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | TAF Based ART | TDF Based ART | Total |
|---|---|---|---|
| United States | 15 | 11 | 26 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Apr 2019 to primary completion in Jul 2021, 27 months.
Results were first posted in May 2022, 10 months after primary completion.
Of 29 phase 1/2 interventional studies under Acquired Immunodeficiency Syndrome, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 24. This study's 27 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2022. You cannot join it, but the record below documents what was studied.
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Acquired Immunodeficiency Syndrome →
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