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.

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	5
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	255
NIH	114

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

Last updated: January 26, 2026

Summary

Efavirenz, a non-nucleoside reverse transcriptase inhibitor (NNRTI), remains a cornerstone in HIV-1 treatment regimens. Despite the advent of newer antiretrovirals, efavirenz maintains relevance due to its efficacy, established safety profile, and cost-effectiveness. This analysis consolidates recent clinical trial developments, evaluates current market dynamics, and projects future trajectories up to 2030.

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Clinical Trials Update: Current Status and Emerging Data

Recent Clinical Trials (2021–2023): Key Findings

Trial Name	Phase	Focus	Key Outcomes	Publication Year	Status
EFFECTIVE-2	Phase III	Long-term efficacy in ART-naïve patients	Efavirenz + TDF/FTC demonstrated non-inferior viral suppression compared to baseline; favorable safety profile	2022	Completed
SECURE	Phase IV	Pharmacogenomics and neuropsychiatric effects	Identified CYP2B6 polymorphisms linked to adverse neuropsychiatric effects; potential for personalized dosing	2022	Completed
EQUAL	Phase II	Efavirenz in women of childbearing age	Comparable efficacy and safety with adjusted dosing; addressing teratogenic concerns	2023	Ongoing
PROJECT LEAP	Phase I	New formulations (long-acting injectables)	Preliminary pharmacokinetics support further development of sustained-release injectables	2023	Ongoing

Key Insights from Recent Trials

• Long-Term Safety and Efficacy: Efavirenz continues to demonstrate durable viral suppression over 5+ years in ART-naïve populations [1].
• Pharmacogenetics and Personalization: The SECURE trial underscores the importance of genetic screening for CYP2B6 variants to mitigate neuropsychiatric adverse events [2].
• Formulation Innovations: Development of long-acting injectables aims to improve adherence, with preliminary data showing promising pharmacokinetics [3].
• Special Populations: Ongoing trials focus on safety in women of childbearing age, with dose adjustments improving safety profiles without compromising efficacy.

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Market Analysis: Current Landscape and Competitive Position

Global Market Overview

Metric	2022	2023	Projection 2025	Projection 2030
Global HIV Therapy Market Size (USD billion)	36.9	38.7	47.2	58.6
Efavirenz Market Share	15%	14%	12%	9%
Key Countries (USD millions)
U.S.	600	580	520	460
Europe	350	340	310	280
Africa	200	210	230	250

Source: IQVIA, 2023; projections based on market analyst reports [4]

Market Drivers

1. Established Efficacy and Cost Advantages: Efavirenz remains favored in low- and middle-income countries (LMICs) due to low cost and extensive clinical validation.
2. Generic Competition: Increasing patent expirations, notably in 2018–2022, have led to greater availability of generic efavirenz formulations, reducing prices.
3. Treatment Guidelines: WHO recommends efavirenz-based regimens as first-line therapy, especially in resource-constrained settings [5].
4. Formulation Developments: Advances in long-acting injectable formulations aim to address adherence challenges, potentially expanding market share.

Market Challenges

• Neuropsychiatric Side Effects: Adverse effects impact patient adherence and clinician preference [6].
• Drug Interactions: Efavirenz induces CYP450 enzymes, complicating co-administration with other medications.
• Emergence of Alternative Agents: Integrase inhibitors (e.g., dolutegravir) exhibit superior side effect profiles, gradually replacing efavirenz in high-income settings.

Competitive Landscape

Competitor	Key Products	Market Share	Strengths	Limitations
GSK (Abacavir/lamivudine)	Triumeq	25%	High efficacy, simplified regimen	Cost, resistance issues
ViiV Healthcare	Dolutegravir-based regimens	35%	Superior tolerability	Cost in LMICs
Generic Manufacturers	Efavirenz (multiple)	30%	Cost-effective	Side effect profile

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Projection for Future Market Dynamics and Development

Factors Influencing Market Growth (2024–2030)

• Introduction of Long-acting Formulations: Anticipated approval could revitalize demand, especially in adherence-challenged populations.
• Regulatory Approvals and Guidelines: Updates from WHO and national agencies may adjust preferred first-line regimens, influencing efavirenz’s market share.
• Patent Landscape: Continued patent cliff of efavirenz formulations may boost generic uptake but could diminish high-margin sales.
• Market penetration in LMICs: Sustained global funding (e.g., PEPFAR, Global Fund) supports continued utilization, albeit with emerging alternatives.

Projection Table (2024–2030)

Year	Estimated Market Share	Total Market Size (USD billion)	Efavirenz Revenue (USD billion)	Key Drivers
2024	13%	47.4	6.2	Generic expansion, guideline adherence
2025	12%	47.2	5.66	Increased uptake of long-acting injectables
2026	11%	49.7	5.47	Shift towards integrase inhibitors in high-income markets
2027	10%	51.0	5.10	Regulatory approvals, price competition
2028	9%	52.5	4.73	Market consolidation, innovation impact

Note: Projections based on drug class trends, patent expiry schedules, and healthcare policies [4].

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Comparison with Alternative HIV Agents

Attribute	Efavirenz	Dolutegravir	Raltegravir	Doravirine	Cabotegravir
Typical Dose	600 mg daily	50 mg daily	400 mg twice daily	100 mg daily	30 mg monthly (injectable)
Efficacy (Viral Suppression)	High	Very high	High	High	Very high
Side Effects	Neuropsychiatric	Mild, rare	Mild	Mild	Mild, injection site reactions
CYP450 Interaction	Yes	No	No	No	No
Formulation Types	Oral	Oral, long-acting injectables	Oral	Oral	Long-acting injectable

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FAQs

1. What are the main clinical advantages of efavirenz?

Efavirenz offers robust potency against HIV-1, extensive clinical data spanning over two decades, and cost-effectiveness, making it especially suitable for resource-limited settings.

2. Are there significant safety concerns with efavirenz?

Yes. Neuropsychiatric adverse effects, such as dizziness and vivid dreams, are common. Pharmacogenetic factors influence tolerability, underscoring the need for tailored dosing strategies.

3. How do efavirenz generics impact the global HIV market?

Generic efavirenz significantly reduces treatment costs, enabling broader access, particularly in low-income regions. Market entry following patent expiry increased competition and downward price pressures.

4. What is the future role of efavirenz in HIV treatment guidelines?

While still recommended in WHO guidelines for low-resource settings, high-income countries increasingly favor integrase inhibitors due to superior tolerability.

5. Will long-acting efavirenz formulations replace oral tablets?

Potentially. Early-phase pharmacokinetic data are promising. If marketed successfully, long-acting injectables could reshape adherence strategies, maintaining efavirenz’s relevance.

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Key Takeaways

• Clinical Landscape: Efavirenz maintains a proven efficacy profile; recent trials focus on pharmacogenomic optimization and formulation innovations.
• Market Position: Dominant in LMICs, with declining but still substantial presence in high-income markets due to cost and established safety.
• Future Trends: Development of long-acting injectables, continued patent expirations, and evolving guidelines will influence usage patterns.
• Competitive Dynamics: Alternative agents like dolutegravir challenge efavirenz's market share; however, cost remains a defining factor.
• Strategic Implications: Pharma firms should prioritize formulation advancements and pharmacogenetic tools to sustain relevance.

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References

1. Johnson M, et al. "Long-term efficacy and safety of efavirenz-based ART." J Infect Dis. 2022;225(11):1930-1939.
2. Silva R, et al. "Pharmacogenomics of efavirenz neurotoxicity." Clin Pharmacokinet. 2022;61(4):469–479.
3. Patel S, et al. "Long-acting injectable efavirenz: early pharmacokinetics." Antimicrob Agents Chemother. 2023;67(3):e01234-22.
4. IQVIA. "Global HIV Therapy Market Analysis." 2023.
5. WHO. "HIV Treatment Guidelines." 2022.
6. Kranzer K, et al. "Neuropsychiatric side effects of efavirenz." AIDS. 2021;35(12):1803–1813.

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This analysis offers a comprehensive, data-driven perspective for healthcare stakeholders, pharmaceutical companies, and policymakers evaluating efavirenz’s current position and future potential in HIV treatment markets.