Efavirenz for HIV

("TACKITON Trial)

Recruiting at 1 trial location

Overseen By Colin Kovacs, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Toronto

Must be taking: Antiretrovirals

Must not be taking: Protease inhibitors

Disqualifiers: Psychiatric conditions, Cognitive impairment, Malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

Duration: 8 weeks

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to tackling HIV using Efavirenz, a drug long used to control the virus. The study aims to determine if Efavirenz can reduce the persistent traces of HIV that remain despite regular treatment. It targets individuals who have been on HIV treatment for over four years but still have a small amount of the virus in their blood. Participants should maintain a stable treatment routine without protease inhibitors. Success in this trial could improve HIV management and potentially lead to larger studies aiming for a cure. As an unphased trial, it offers a unique opportunity to contribute to groundbreaking research that could enhance HIV treatment strategies.

Will I have to stop taking my current medications?

The trial does not require you to stop your current HIV medications, but you must not be taking a protease inhibitor or efavirenz as part of your current regimen. You will need to add efavirenz to your existing treatment.

Is there any evidence suggesting that Efavirenz is likely to be safe for humans?

Research has shown that Efavirenz, a well-known HIV medication, is generally safe for people and has been used for many years to treat HIV. One study found that about 35% of pregnancies using Efavirenz had negative birth outcomes, similar to other HIV treatments, indicating that Efavirenz is as safe as other HIV drugs.

Efavirenz is also considered safe for various groups, including pregnant women and children. Another study found that women with HIV who used Efavirenz had better survival rates compared to those on other treatments. While side effects can occur, the long history of Efavirenz in HIV treatment suggests that most people tolerate it well.

These findings provide strong evidence of Efavirenz's safety for those considering joining this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Efavirenz is unique because it is being explored as an addition to existing antiretroviral therapy (ART) for people with high adherence to their treatment regimen. Unlike other HIV medications that are often combined in multi-drug regimens, Efavirenz is being tested as a single add-on drug to see if it can enhance the effectiveness of current ART. Researchers are excited about this treatment because it offers a potential boost to the standard therapy, possibly increasing the suppression of the virus and improving patient outcomes without the need for additional complex drug combinations.

What evidence suggests that Efavirenz might be an effective treatment for HIV?

Research shows that Efavirenz (EFV) has played an important role in HIV treatment for many years by stopping the virus from growing in the body. Recent studies have found that EFV might offer another benefit: it can kill cells infected with HIV by activating a natural process within these cells. This ability could be especially useful for individuals who maintain low but steady levels of the virus, even with regular medication. While EFV has been used to control the virus, its capacity to target and destroy infected cells offers hope for reducing the hidden stores of the virus in the body. This trial will explore adding Efavirenz for people with high adherence to ART, making EFV a promising option for challenging cases of HIV. ^{6 7 8 9 10}

Who Is on the Research Team?

Mario Ostrowski, MD

Principal Investigator

University of Toronto

Colin Kovacs, MD

Principal Investigator

University of Toronto

Are You a Good Fit for This Trial?

This trial is for individuals with HIV who are on antiretroviral therapy but still have low levels of virus in their blood (40-400 copies/ml). It's designed to test if adding Efavirenz, a drug that may kill HIV-infected cells, can reduce the virus further. Participants must be currently adhering to ART and have detectable non-suppressive viremia.

Inclusion Criteria

Documented HIV diagnosis

At least 4 HIV viral loads >20 and < 400 copies/ml over the past two years

No evidence of EFV resistance by plasma virus sequencing at screening visit

Exclusion Criteria

Participants who would have difficulty participating in a trial due to non-compliance

Any illness or conditions including acute illnesses that, in the opinion of the investigator, may affect the safety of the participant or the evaluation of any study endpoints

No active medications / illicit drugs that could adversely affect study compliance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Baseline

Baseline assessments including blood draws and optional leukapheresis; initiation of Efavirenz treatment

1 day

1 visit (in-person)

Treatment

Participants receive Efavirenz 600 mg daily for 8 weeks to evaluate its impact on reducing HIV persistence

8 weeks

4 visits (in-person) at weeks 1, 3, 5, and 7

Follow-up

Participants are monitored for safety and effectiveness after discontinuation of Efavirenz

8 weeks

3 visits (in-person) at weeks 9, 12, and 16

What Are the Treatments Tested in This Trial?

Interventions

• Efavirenz

Trial Overview The study tests whether Efavirenz (EFV), traditionally used to suppress HIV replication, can also act as a 'TACK' compound—targeting and killing HIV-infected cells. The goal is to see if EFV added to existing ART regimens can help eliminate these infected cells and achieve undetectable viral levels.

How Is the Trial Designed?

Group I: Addition of Efavirenz in people with high adherence to ART. Experimental Treatment 1 Intervention

Single arm - Participants will be prescribed Efavirenz 600 mg q hs x 2 months starting at baseline visit (visit 2)

Who Is Running the Clinical Trial?

University of Toronto

Lead Sponsor

Trials

739

Recruited

1,125,000+

Maple Leaf Research

Collaborator

Trials

5

Recruited

280+

Ontario HIV Treatment Network

Collaborator

Trials

15

Recruited

5,300+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Published Research Related to This Trial

In the SENSE trial involving 157 treatment-naive HIV-infected individuals, etravirine was associated with significantly fewer neuropsychiatric adverse events compared to efavirenz, with 16.5% of patients on etravirine experiencing such events versus 46.2% on efavirenz (P < 0.001).

Both treatments showed similar effectiveness in reducing HIV-RNA levels and increasing CD4 cell counts after 12 weeks, indicating that etravirine can be a safer alternative without compromising treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of neuropsychiatric adverse events during 12 weeks of treatment with etravirine and efavirenz in a treatment-naive, HIV-1-infected population. Nelson, M., Stellbrink, HJ., Podzamczer, D., et al.[2022]

Efavirenz (EFV) is generally safe for first-line treatment in HIV-positive individuals, with over 90% of patients remaining on the regimen after an average follow-up of 78 weeks, indicating good tolerability.

While EFV showed a higher relative risk of discontinuation due to adverse events compared to several other treatments, the absolute differences were minimal (less than 5%), and severe adverse events were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Safety and Neuropsychiatric Adverse Events Associated With Efavirenz Use in First-Line Antiretroviral Therapy: A Systematic Review and Meta-Analysis of Randomized Trials. Ford, N., Shubber, Z., Pozniak, A., et al.[2022]

Efavirenz is an effective first-line treatment for HIV-1 infection when combined with two nucleoside analogue reverse transcriptase inhibitors, supported by numerous clinical trials demonstrating its antiretroviral efficacy.

While efavirenz allows for convenient once-daily dosing due to its long half-life, it can lead to neuropsychiatric side effects that may persist for up to 2 years, highlighting the importance of adherence to therapy to prevent viral resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efavirenz: a review. Vrouenraets, SM., Wit, FW., van Tongeren, J., et al.[2020]

In a study of 450 HIV-1-infected patients, the regimen combining efavirenz with zidovudine and lamivudine achieved undetectable HIV-1 RNA levels in 70% of participants, significantly outperforming the indinavir-based regimen, which had only 48% success.

The efavirenz-based treatment was better tolerated, with fewer patients discontinuing due to adverse events (27% vs. 43% for the indinavir group), highlighting its safety and efficacy as an antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. Study 006 Team. Staszewski, S., Morales-Ramirez, J., Tashima, KT., et al.[2022]

Efavirenz is an effective HIV-1 reverse transcriptase inhibitor that shows strong antiviral activity in treatment-naïve patients when combined with two nucleoside analogues or a protease inhibitor, demonstrating similar or potentially superior effects compared to indinavir-based therapy over 48 weeks.

Patients using efavirenz experienced fewer discontinuations due to adverse events compared to those on indinavir, although some side effects like rash and CNS disturbances were noted, typically resolving within the first weeks of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efavirenz: shifting the HAART paradigm in adult HIV-1 infection. Moyle, GJ.[2019]

In a study of 1,033 HIV-infected adults starting efavirenz treatment, 29.3% experienced adverse events (AEs), primarily CNS disturbances, but these were generally not severe and led to treatment interruption in only 8.23% of cases.

The safety profile of efavirenz is favorable even among a population with a high rate of intravenous drug use, with no significant associations found between prior psychiatric issues or drug use and increased AEs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerance of efavirenz in different antiretroviral regimens: results from a national multicenter prospective study in 1,033 HIV-infected patients. Pérez-Molina, JA.[2022]

In a 48-week trial involving 355 HIV-infected patients, the use of efavirenz (EFV) was not associated with an increased risk of depressive disorders or suicide attempts compared to protease inhibitor-based treatments.

Key risk factors for depression included younger age and a history of depressive disorders, highlighting the importance of monitoring these patients for early detection and management of depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of efavirenz is not associated with a higher risk of depressive disorders: a substudy of the randomized clinical trial ALIZE-ANRS 099. Journot, V., Chene, G., De Castro, N., et al.[2020]

In a study of 6259 patients starting highly active antiretroviral therapy (HAART) from 2000 to 2010, those treated with efavirenz (EFV) had significantly better outcomes, achieving a composite outcome of success (COS) more frequently than those on boosted protease inhibitors (PIs).

Patients on boosted PIs not only had lower rates of virological suppression but also developed AIDS more frequently and had higher mortality rates compared to those on EFV, highlighting the efficacy and safety advantages of EFV in HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of efavirenz or atazanavir/ritonavir is associated with better clinical outcomes of HAART compared to other protease inhibitors: routine evidence from the Italian MASTER Cohort. Postorino, MC., Prosperi, M., Quiros-Roldan, E., et al.[2020]

In a study of 314 patients, efavirenz (EFV) combined with nucleoside reverse transcriptase inhibitors effectively suppressed HIV-1 RNA levels, achieving <50 copies/mL in 82% of treatment-naïve patients compared to 56% in heavily pretreated patients after 80 weeks.

The treatment led to significant increases in CD4 cell counts, with no AIDS-defining events reported, highlighting EFV's efficacy and safety in managing HIV, especially in those who had not previously received antiretroviral therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of an efavirenz-containing regimen: an open-label, multicenter study. Hartmann, M., Rump, A., Brust, J., et al.[2020]

Efavirenz has been shown to be more effective than other treatments like the boosted protease inhibitor lopinavir and is a key component of highly active antiretroviral therapy (HAART) for HIV, maintaining virological and immunological responses for up to 7 years in patients.

While generally well tolerated, efavirenz can cause side effects such as rash and neuropsychiatric disturbances, which usually resolve over time, but adherence to the treatment is crucial to prevent resistance mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efavirenz: a decade of clinical experience in the treatment of HIV. Maggiolo, F.[2021]

In a study of 2920 HIV-infected adults on efavirenz therapy over 8834 person-years, the incidence of adverse drug reactions (ADRs) was found to be 40.3 per 1000 person-years, with lipodystrophy and neuropsychiatric disorders being the most common.

Neuropsychiatric ADRs were particularly prevalent among women, younger patients, those with advanced HIV disease, and those on specific drug regimens, highlighting the need for ongoing monitoring and management of these side effects in patients receiving efavirenz-based treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence and predictors of adverse drug events in an African cohort of HIV-infected adults treated with efavirenz. Abah, IO., Akanbi, M., Abah, ME., et al.[2022]

In a study of 310 severely immunosuppressed HIV-1-infected patients, those treated with an efavirenz (EFV)-based regimen had a significantly higher rate of achieving a viral load of less than 400 copies/mL after 12 months compared to those on a protease inhibitor (PI)-based regimen (69.4% vs. 45.1%).

Despite the superior virologic response with EFV, the time to treatment failure was shorter for the PI-based regimen, indicating that while EFV may be more effective in reducing viral load, it does not lead to better overall treatment durability in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical, virologic, and immunologic response to efavirenz-or protease inhibitor-based highly active antiretroviral therapy in a cohort of antiretroviral-naive patients with advanced HIV infection (EfaVIP 2 study). Pulido, F., Arribas, JR., Miró, JM., et al.[2020]

Citations

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Clinical predictors of efavirenz-based regimen treatment ... 59.5% of patients who experienced ≥ 1 ADE versus 81% of those who did not experience any ADE were estimated to continue treatment for up to 24 months with no ...

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and Dolutegravir-based Antiretroviral Therapy During Acute ... Compared with efavirenz-based regimens, initiating dolutegravir-based regimens during acute human immunodeficiency virus was associated with greater improv.

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Safety, Tolerability and Pharmacokinetics of Efavirenz in ... Phenotype resistance: FTC: > 3.1* the 50% inhibitory concentration (IC50) of the control strain; EFV: > 3.3* IC50 ; ddI: > 2.6*IC50. Virologic failure: <1 log10 ...

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Efavirenz (Sustiva) - Safety and Toxicity in Pregnancy | NIH Safety of pediatric HIV ... In utero efavirenz exposure and neurodevelopmental outcomes in HIV-exposed uninfected children in Botswana.

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Full article: Comparative Safety and Changes in ... This study aimed to determine the safety and changes in immunologic and virologic parameters of DTG compared with EFV-based ART as first-line HIV treatment ...