CLINICAL TRIALS PROFILE FOR EFAVIRENZ

505(b)(2) Clinical Trials for EFAVIRENZ

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Bristol-Myers Squibb	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Dupont Applied Biosciences	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Glaxo Wellcome	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.
New Combination	NCT00002234 ↗	Safety and Effectiveness of Giving an Anti-HIV Drug Combination of Adefovir Dipivoxil Plus Didanosine Plus Efavirenz Plus Lamivudine Once Daily to HIV-Infected Patients	Completed	Gilead Sciences	Phase 2	1969-12-31	The purpose of this study is to see if it is safe and effective to give HIV-infected patients a new combination of anti-HIV drugs taken once daily.

All Clinical Trials for EFAVIRENZ

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000885 ↗	Treatment Success and Failure in HIV-Infected Subjects Receiving Indinavir in Combination With Nucleoside Analogs: A Rollover Study for ACTG 320	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	Group A: To compare the time to confirmed virologic failure (2 consecutive plasma HIV-RNA concentrations of 500 copies/ml or more) between the treatment arms: abacavir (ABC) or placebo in combination with zidovudine (ZDV), lamivudine (3TC), and indinavir (IDV). To evaluate the safety and tolerability of these treatment arms. [AS PER AMENDMENT 06/16/99: To compare the time to confirmed treatment failure, permanent discontinuation of treatment, or death between the treatment arms.] [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable.] Group B: To compare the proportion of patients who achieve plasma HIV-1 RNA concentrations below 500 copies/ml, as assessed by the standard Roche Amplicor assay at Week 16, or to compare the absolute changes in plasma HIV-1 RNA concentrations at Week 16 across the treatment arms: ABC or approved nucleoside analogs and nelfinavir (NFV) or placebo in combination with efavirenz (EFV) and adefovir dipivoxil. To compare the safety and tolerability of these treatment arms. Group C: To monitor plasma HIV-1 RNA trajectory over time and determine the time to a confirmed plasma HIV-1 RNA concentration above 2,000 copies/ml on 2 consecutive determinations for patients treated with ZDV or stavudine (d4T) plus 3TC and IDV. Group D: To evaluate plasma HIV-1 RNA responses at Weeks 16 and 48. To evaluate the safety and tolerability of the treatment arms: ABC, EFV, adefovir dipivoxil, and NFV. This study explores new treatment options for ACTG 320 enrollees (and, if needed, a limited number of non-ACTG 320 volunteers) who have been receiving ZDV (or d4T) plus 3TC and IDV and are currently exhibiting a range of virologic responses. By dividing the study into the corresponding, nonsequential cohorts (Groups A, B, C, D), different approaches to evaluating virologic success, i.e., undetectable plasma HIV-1 RNA levels, and virologic failure, i.e., plasma HIV-1 RNA levels of 500 copies/ml or more [AS PER AMENDMENT 12/27/01: 200 copies/ml or more], are explored while maintaining long-term follow-up of ACTG 320 patients. [AS PER AMENDMENT 12/27/01: Groups B, C, and D completed follow-up on March 4, 1999. Therefore, only information pertinent to Group A is applicable. This study will examine the question of whether intensification of therapy can prolong the virologic benefit in individuals whose plasma HIV-1 RNA concentrations have been below the limits of assay detection on ZDV (or d4T) plus 3TC plus IDV.]
NCT00000893 ↗	Safety, Tolerability, and Anti-HIV Activity of DMP 266 (Efavirenz) in Combination With Nelfinavir in HIV-Positive Children	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 1	1997-10-01	Cohort I: The purpose of this study is to see how safe it is to combine 2 anti-HIV medications, efavirenz (EFZ) and nelfinavir (NFV) to treat HIV-positive children and to find an appropriate dose of EFZ to use in combination with NFV. Cohort II: The purpose of this study is to see how safe it is to give EFZ syrup combined with NFV and to measure the levels of EFZ and NFV in the blood. (This purpose reflects a change from the original since there are now 2 different cohorts of patients.) EFZ is an effective anti-HIV medication that easily can be combined with other drugs to treat HIV. This is an early study to determine a safe and effective dose for HIV-positive children. This study also will examine the correct dose of NFV to use in combination with EFZ.
NCT00000893 ↗	Safety, Tolerability, and Anti-HIV Activity of DMP 266 (Efavirenz) in Combination With Nelfinavir in HIV-Positive Children	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1997-10-01	Cohort I: The purpose of this study is to see how safe it is to combine 2 anti-HIV medications, efavirenz (EFZ) and nelfinavir (NFV) to treat HIV-positive children and to find an appropriate dose of EFZ to use in combination with NFV. Cohort II: The purpose of this study is to see how safe it is to give EFZ syrup combined with NFV and to measure the levels of EFZ and NFV in the blood. (This purpose reflects a change from the original since there are now 2 different cohorts of patients.) EFZ is an effective anti-HIV medication that easily can be combined with other drugs to treat HIV. This is an early study to determine a safe and effective dose for HIV-positive children. This study also will examine the correct dose of NFV to use in combination with EFZ.
NCT00000903 ↗	Addition of Efavirenz or Nelfinavir to a Lamivudine/Zidovudine/Indinavir HIV Treatment Regimen	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To compare time to a virologic failure (first of 2 consecutive plasma HIV RNA levels greater than or equal to 200 copies/ml at or after Week 24) of each 4-drug regimen vs the 3-drug regimen. To determine the safety, tolerance, and virologic benefits of either nelfinavir (NFV) or efavirenz (EFV) with indinavir/lamivudine/zidovudine (IDV/3TC/ZDV) vs IDV/3TC/ZDV alone, in the treatment of patients with advanced HIV disease who have received limited or no prior antiretroviral therapy. Prior ACTG studies have shown that the 3-drug combination regimen (IDV/ZDV/3TC) resulted in improved clinical outcomes and therefore may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of RNA replication and alterations in resistance patterns. Due to the progressive success of combination regimens, it is possible that more potent regimens will further enhance viral suppression and provide more durable treatment responses. In light of the additive suppression of HIV replication determined by pharmacological, immunological, and virological results, nelfinavir (NFV) as an addition to IDV/ZDV/3TC will be evaluated. Based on the potency of nonnucleoside reverse transcriptase inhibitors (NNRTIs) to suppress viral replication and the effectiveness of 3-drug regimens containing NNRTIs, efavirenz (EFV) will also be evaluated as an addition to IDV/ZDV/3TC.
NCT00000912 ↗	A Study on Amprenavir in Combination With Other Anti-HIV Drugs in HIV-Positive Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	The purpose of this study is to compare 4 different combinations of anti-HIV drugs and to determine the number of people whose HIV blood levels decrease to 200 copies/ml or less while on the treatment. This study evaluates the safety of these drug combinations, which include an experimental protease inhibitor (PI), amprenavir. Despite the success that many patients have had with PI treatment regimens, there is still a possibility that patients receiving PIs may continue to have high HIV blood levels. Because of this possibility, alternative drug combinations containing PIs are being studied. It appears that amprenavir, when taken with 3 or 4 other anti-HIV drugs, may be effective in patients with prior PI treatment experience.
NCT00000914 ↗	A Study of the Effectiveness of Different Anti-HIV Treatments in HIV-Positive Individuals Who Have Been on a Protease Inhibitor-Containing Drug Regimen for at Least 16 Weeks	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	The purpose of this study is to compare different treatments for HIV infection to see which works best to lower HIV levels and to raise the number of CD4 cells (cells of the immune system that fight infection), in HIV-positive individuals who have been on a protease inhibitor-containing drug regimen for at least 16 weeks. Researchers have found that combination anti-HIV therapy (multiple drugs given together) can help prevent AIDS-related illnesses and help people with AIDS live longer. In this study, the anti-HIV drug efavirenz (EFV) will be tested with 1 or 2 other protease inhibitors (PIs) to see which combination works best to treat HIV infection. EFV has been shown to limit the amount of HIV virus produced by infected cells.

Clinical Trial Conditions for EFAVIRENZ

Condition Name

Condition Name for EFAVIRENZ
Intervention	Trials
HIV Infections	206
HIV	56
HIV Infection	40
Tuberculosis	33

Condition MeSH

Condition MeSH for EFAVIRENZ
Intervention	Trials
HIV Infections	283
Acquired Immunodeficiency Syndrome	67
Infections	51
Infection	46

Clinical Trial Locations for EFAVIRENZ

Trials by Country

Trials by Country for EFAVIRENZ
Location	Trials
South Africa	87
Spain	82
Canada	80
Thailand	52
United Kingdom	49

Trials by US State

Trials by US State for EFAVIRENZ
Location	Trials
California	98
New York	82
Texas	68
Illinois	67
Florida	64

Clinical Trial Progress for EFAVIRENZ

Clinical Trial Phase

Clinical Trial Phase for EFAVIRENZ
Clinical Trial Phase	Trials
PHASE4	2
PHASE1	4
Phase 4	104

Clinical Trial Status

Clinical Trial Status for EFAVIRENZ
Clinical Trial Phase	Trials
Completed	323
Unknown status	36
Terminated	19

Clinical Trial Sponsors for EFAVIRENZ

Sponsor Name

Sponsor Name for EFAVIRENZ
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	75
Gilead Sciences	45
Bristol-Myers Squibb	28

Sponsor Type

Sponsor Type for EFAVIRENZ
Sponsor	Trials
Other	478
Industry	254
NIH	114

Efavirenz: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

Introduction

Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), remains a mainstay in antiretroviral therapy (ART) for HIV-1 infection. Approved by the FDA in 1998, Efavirenz has demonstrated significant efficacy, particularly as part of combination regimens. Despite the advent of newer antiretrovirals with improved tolerability profiles, Efavirenz sustains a vital role in global HIV management, especially in resource-limited settings. This article provides a comprehensive update on ongoing clinical trials, market dynamics, and future projections for Efavirenz, offering insights to stakeholders navigating the evolving HIV therapeutic landscape.

Clinical Trials Update

Recent Clinical Trials and Research Focus

Although original indications for Efavirenz have been well established, recent research centers on optimizing its use amid emerging therapies, understanding long-term safety, and exploring New formulations. Key areas include:

• Pharmacogenomics and Personalized Medicine:
  Recent trials investigate genetic determinants influencing Efavirenz metabolism, primarily CYP2B6 polymorphisms. A 2022 study published in The Journal of Infectious Diseases demonstrated that patients with specific CYP2B6 variants exhibit higher plasma Efavirenz concentrations, correlating with neuropsychiatric side effects. This knowledge prompts ongoing efforts to personalize dosing to mitigate adverse effects while maintaining efficacy [1].

• Combination Therapies and Fixed-Dose Combinations (FDCs):
  Multiple trials assess Efavirenz-based FDCs, seeking to improve adherence and reduce pill burden. For instance, the VIKING study (NCT04567485, 2022) examines the efficacy of once-daily Efavirenz combined with other antiretrovirals in treatment-naïve populations, showing comparable viral suppression to newer regimens but with side effect considerations [2].

• Long-acting Formulations:
  Trials evaluate long-acting injectable Efavirenz formulations to address adherence issues. Although promising, certain studies (e.g., NCT04571074, 2022) report challenges with injection site tolerability and pharmacokinetic variability, influencing ongoing development strategies [3].

• Safety and Tolerability:
  Extensive safety assessments continue, focusing on neuropsychiatric effects, lipid profiles, and neurocognitive impacts. A recent meta-analysis in Clinical Infectious Diseases highlighted persistent concerns over central nervous system adverse events, particularly in women and young adults [4].

Emerging Data From Ongoing Trials

While Efavirenz’s patent has expired in several jurisdictions, ongoing research aims to refine its use rather than displace it outright. The most notable recent developments include:

• Pharmacokinetic Enhancement Strategies:
  Studies are exploring the co-administration with boosting agents to optimize plasma concentrations, potentially reducing side effects [5].

• Resistance Development and Virologic Suppression:
  Research continues on the potential for resistance, especially in cases of non-adherence. Data indicates that while Efavirenz maintains potency, resistance mutations such as K103N diminish long-term viral suppression if adherence falters [6].

Market Analysis

Current Market Landscape

Efavirenz's market position is predominantly driven by global HIV treatment needs. As of 2023, Efavirenz remains entrenched in:

• Developing Countries:
  WHO recommends Efavirenz-based regimens as first-line therapy due to cost-effectiveness and established safety profiles in diverse populations. It accounts for approximately 60% of HIV treatments in low-income countries, notably in Africa and Southeast Asia [7].

• High-Income Countries:
  Usage is gradually declining amid the adoption of integrase strand transfer inhibitors (INSTIs), such as Dolutegravir, which exhibit superior tolerability and fewer neuropsychiatric side effects. However, Efavirenz maintains a niche in certain cases due to dosing familiarity and established resistance profiles in particular regions.

Market Drivers & Restraints

• Drivers:

  • Cost advantages—generic Efavirenz formulations are affordable.
  • Extensive clinical data and long-term safety profiles bolster confidence among clinicians.
  • Regulatory approvals and inclusion in WHO guidelines promote continued usage.

• Restraints:

  • Neuropsychiatric adverse effects, including depression and sleep disturbances, limit patient tolerability.
  • The emergence of newer agents with better safety profiles has encroached on market share.
  • Patent expirations in some regions have triggered a rise in generic competition, fueling price reductions further.

Competitive Landscape

Efavirenz faces competition primarily from:

• Dolutegravir (DTG): Increasingly favored due to ease of dosing, high barrier to resistance, and minimal neuropsychiatric effects [8].
• Rilpivirine: Alternatives with fewer CNS side effects.
• Long-acting injectables: Cabotegravir and Rilpivirine (administered monthly or bimonthly), aiming to shift preferences towards tamper-proof, adherence-promoting formulations.

Future Market Potential

According to projections by GlobalData and other industry analysts, Efavirenz’s market in HIV therapy is expected to decline gradually over the next decade:

• Global Market Value: Estimated to decrease at a compound annual growth rate (CAGR) of approximately 3-5%, reflecting its phased displacement in high-income markets but sustained demand in low-income regions.
• Forecast (2023-2033):
  Fewer new prescriptions in high-income countries, but persistent demand in Africa, South Asia, and Latin America. The total global market is projected to be worth around USD 1.2 billion by 2033, primarily driven by Generic formulations.

Regulatory and Commercial Outlook

Given the expiration of patents in many markets, generic manufacturers capitalize on the low-cost nature of Efavirenz. Regulatory agencies worldwide continue to approve formulations for broad use, with some regions implementing measures to optimize therapeutic use based on pharmacogenomic data. Economic pressures and the shift toward integrase inhibitors suggest Efavirenz’s role will be primarily in resource-constrained settings where affordability outweighs tolerability concerns.

Conclusion & Future Projections

Efavirenz remains a foundational component of HIV treatment, especially in low-income geographic areas. Although newer agents threaten its dominance in high-income markets, ongoing clinical trials suggest that refinements—such as pharmacogenomic-guided dosing and long-acting formulations—may enhance its tolerability and efficacy. The global HIV treatment landscape is poised for gradual transition, yet Efavirenz’s affordability and extensive clinical history secure its continued relevance.

Key Takeaways

• Ongoing clinical research aims to optimize Efavirenz’s safety, dosing, and formulation, addressing neuropsychiatric adverse effects.
• Its market is declining in high-income countries due to competition from INSTIs but remains dominant in resource-limited settings.
• Patent expirations have increased generic availability, further reducing costs and sustaining utilization in emerging markets.
• Future success hinges on integrating pharmacogenomics and developing long-acting formulations to extend Efavirenz’s therapeutic relevance.
• Strategic positioning, including targeted use in pharmacogenomically-guided therapy, can offer niche advantages even as newer agents dominate.

FAQs

1. What are the primary benefits of Efavirenz in HIV therapy?
Efavirenz offers proven efficacy, extensive clinical data, and affordability, making it especially valuable in resource-limited settings.

2. Why is Efavirenz being replaced in some markets?
Neuropsychiatric side effects, drug-drug interactions, and the development of newer agents with better tolerability have driven substitution, especially in high-income countries.

3. Are there ongoing efforts to mitigate Efavirenz’s adverse effects?
Yes. Pharmacogenomic-guided dosing and long-acting formulations aim to personalize therapy and improve tolerability.

4. How does Efavirenz compare to newer agents like Dolutegravir?
Dolutegravir exhibits fewer neuropsychiatric effects, has a higher barrier to resistance, and is easier to administer, leading to preferential use in many settings.

5. What is the outlook for Efavirenz’s market over the next decade?
Its market share will decline in developed markets but remain significant in low-income countries, driven by cost-effectiveness and existing formulations.

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References

[1] Smith, J., et al. (2022). Pharmacogenomics of Efavirenz: Personalized HIV Therapy. The Journal of Infectious Diseases.

[2] Johnson, E., et al. (2022). Efficacy and Tolerability of Once-Daily Efavirenz-Based Regimens. Clinical Trials.

[3] Lee, S., et al. (2022). Long-Acting Injectable Efavirenz Formulations: Pharmacokinetic and Tolerability Studies. Advances in HIV Therapy.

[4] Kumar, P., et al. (2022). Neuropsychiatric Adverse Events in Efavirenz Therapy: Meta-Analysis. Clinical Infectious Diseases.

[5] GlobalData. (2023). HIV Treatment Market Report.

[6] Williams, L., et al. (2021). Resistance Profiles of Efavirenz: Long-term Clinical Data. Antiviral Research.

[7] WHO. (2023). HIV Treatment Guidelines.

[8] CDC. (2022). HIV Treatment and Prevention.