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
Brazil	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

Last updated: July 25, 2026

Efavirenz clinical trials update, market analysis, and exclusivity-driven generic and formulation outlook (2026)

Efavirenz remains a long-established HIV non-nucleoside reverse transcriptase inhibitor (NNRTI) with heavy generic penetration in most markets. Patent exclusivity is functionally expired in major jurisdictions; commercial exposure today is driven by price competitiveness, procurement policies, and fixed-dose combination (FDC) positioning in national HIV programs. Current clinical activity is concentrated in pharmacokinetic, formulation, adherence, and simplified regimens rather than de novo Phase 3 efficacy programs.

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What clinical trials are active or recently completed for efavirenz (2023-2026)?

Which trial types are most common for efavirenz today

Recent efavirenz-focused clinical work has clustered around:

• Switching studies (stable patients on efavirenz-based regimens moving to alternative NNRTIs or maintaining efavirenz for continuity, depending on local guidelines).
• Bioequivalence and formulation trials for generics and FDC products (tablet vs. dispersed vs. pediatric dosing forms).
• Pharmacokinetic characterization in special populations (TB co-therapy, hepatic impairment, pregnancy timing, adolescents).
• Adherence and tolerability studies tied to regimen simplification and counseling strategies.

Why efavirenz trial volume is lower than newer NNRTIs

Efavirenz is off patent in most high-income markets; global trial sponsorship shifts to next-generation NNRTIs and integrase inhibitor platforms. That reduces the incentive for large, brand-funded Phase 3 programs. In practice, the “trial pipeline” is dominated by:

• Regulatory-supporting studies for generic approvals.
• Local evidence generation for guideline inclusion and procurement.

Key endpoints and design patterns

Efavirenz studies in this era most often report:

• Plasma PK parameters (Cmax, AUC, trough levels) and food-effect impacts.
• Safety/tolerability signals (neuropsychiatric events, rash, hepatotoxicity).
• Virologic outcomes where included (switch studies) using time-to-virologic suppression or proportion achieving HIV-1 RNA below a threshold.

Clinical reality: efavirenz remains clinically relevant in many formularies, but the research footprint is increasingly regulatory and formulation-driven, not brand-efficacy driven.

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What is the efavirenz market size, growth outlook, and price trajectory?

Market structure

Efavirenz is sold mainly through:

• Generic supply chains serving public-sector procurement (high-volume, low-margin).
• Combination tablets where efavirenz is one component of an FDC regimen.
• Retail where still used, but displaced by regimens built around dolutegravir and other contemporary options.

Demand drivers

• National HIV program formularies that still include efavirenz-based regimens for cost containment.
• Established clinician familiarity and supply stability.
• Limited substitutions in certain settings due to procurement cycles and guideline lag.

Demand headwinds

• Global shift toward integrase inhibitor-based regimens with improved tolerability and dosing convenience.
• Historical safety concerns (notably neuropsychiatric effects) influencing stewardship and guideline decisions.
• Ongoing price compression from multi-source generic competition.

2026 market projection (directional)

Efavirenz volumes are projected to be:

• Flat to declining in markets where integrase inhibitor regimens dominate procurement.
• Stable to slowly declining in public-sector settings where efavirenz remains on tender lists and FDC supply is entrenched.

Primary variable: tender and guideline inclusion, not clinical efficacy differences.

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What patents protect efavirenz, and when does exclusivity lose impact?

Patent status by practical business lens

Efavirenz is a first-generation NNRTI developed decades ago. In practical terms:

• Brand patent exclusivity in major jurisdictions has long expired.
• The dominant IP constraints now are typically formulation-specific patents (coating, particle size, dispersible forms), manufacturing process claims, and trademark/market authorization holdings rather than core compound patents.

What still can be patent-relevant

Even without active small-molecule exclusivity, patent value can persist through:

• Specific FDC combinations and manufacturing/process patents.
• Pediatric formulation patents (dose forms and dosing strategies).
• Thermally stable or bioavailability-optimized formulations.

Commercial implication: generic entry barriers are now mostly about formulation patents and Orange Book-style listing practices where applicable, plus regulatory data exclusivity for particular products.

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What is the Orange Book status of efavirenz?

Efavirenz is generally treated as off-patent across major markets. Product-level exclusivity, if any, is typically tied to:

• Specific generic sponsor approvals,
• Data exclusivity for certain NDA supplements (rare at this stage),
• Or formulation-specific patent listings associated with branded or particular combination products.

In practice, Orange Book relevance for efavirenz is not usually a gating factor for generic competition for the core active ingredient; it is more often about whether a particular marketed product has still-assertable formulation or method claims.

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Are there Paragraph IV challenges for efavirenz generics?

Paragraph IV litigation historically occurred where:

• A brand or earlier-reference product still had listed patents.
• A generic sought approval by certifying invalidity or non-infringement.

For efavirenz today, Paragraph IV frequency is generally lower than for still-protected drugs because most listed patents tied to efavirenz have expired. Where disputes still occur, they are more likely related to:

• Particular combination formulations,
• Specific dosage forms, or
• Product lifecycle-management patents.

Business bottom line: the probability of new Paragraph IV “big-bang” events for core efavirenz is low; litigation, when it occurs, is usually product-specific.

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How does efavirenz compare with dolutegravir and other NNRTIs for competitive positioning?

Clinical and regimen positioning

• Efavirenz is an NNRTI typically dosed once daily and historically used in first-line regimens.
• Dolutegravir and other integrase inhibitors often displace efavirenz due to tolerability and simplified management in many guideline pathways.
• New NNRTIs (where used) can also compress efavirenz share in regimen choice.

Commercial positioning

Efavirenz competes primarily on:

• Price,
• Procurement reliability,
• Compatibility with existing FDC portfolios.

It competes less on:

• Differentiated safety profiles versus contemporary regimens,
• Convenience and minimized monitoring requirements.

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What formulations are protected for efavirenz, and what does that mean for generic launches?

Formulation/IP hotspots

Formulation and manufacturing claims can still matter for:

• Dispersible tablets for pediatric/adolescent dosing,
• Bioequivalence-optimized tablet designs,
• FDC tablets with specific excipient systems and stability profiles,
• Methods to enhance dissolution and reduce variability across batches.

Generic launch risk framework (current era)

For efavirenz products, generic launch risks usually come from:

• Residual formulation patents associated with specific marketed FDC products.
• Regulatory data dependencies if a product used a unique reference or had special review status (less common after long market presence).
• Manufacturing reproducibility and dissolution specs required for bioequivalence.

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How many patents cover efavirenz-containing fixed-dose combinations (FDCs)?

Why FDC patent mapping matters more than compound mapping

For efavirenz, the commercial product is often an FDC. Patent estates are therefore:

• Product-centric rather than API-centric.
• Concentrated in formulation and manufacturing method claims tied to the exact combination ratio and dosage form.

Practical conclusion: patent landscapes for efavirenz today are best analyzed at the FDC product level (tablet type, strength, and reference listed in regulatory databases), not solely on the base molecule.

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What biosimilar or biologic risks exist for efavirenz?

None. Efavirenz is a small-molecule drug. The competitive threat profile is generic small-molecule entry and formulation-based differentiation, not biosimilars.

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What litigation affects efavirenz today?

Typical litigation topics (modern era)

Where disputes persist, they are usually about:

• Patent infringement related to formulation/process claims for specific efavirenz products or FDCs.
• Regulatory exclusivity disputes tied to reference listed product status.

What this means for market behavior

Litigation, when present, usually impacts:

• Timelines for product-specific launches,
• Settlement-based “carve-out” versions of formulation strength or dosage form,
• Retail vs. tender timing depending on supply commitments.

For efavirenz as an ingredient, litigation impact is typically limited to pockets of remaining product-level IP rather than broad market exclusion.

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What regulatory pathway issues affect efavirenz generics?

Typical approvals

Generic efavirenz products are usually approved under abbreviated pathways where applicable, relying on:

• Bioequivalence to a listed reference product, and
• Mature safety and efficacy datasets.

Key technical constraints

• Bioequivalence requirements for each dosage form and strength.
• Dissolution and stability specifications for FDC and pediatric presentations.
• Labeling alignment with adverse event risk management language (historic neuropsychiatric and rash/hepatotoxicity warnings).

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Market projection by geography: where efavirenz demand is most durable?

Durability pattern

Efavirenz persists where:

• Public-sector procurement uses long-standing regimens with entrenched tender structures.
• Supply chains for integrase-inhibitor alternatives face cost and adoption barriers.
• FDC manufacturing capacity supports continuity.

Projection direction

• Higher durability: lower-middle-income and high-volume public procurement markets that maintain efavirenz in formulary.
• Faster decline: markets with rapid guideline migration and higher adoption of integrase inhibitor-based fixed regimens.

Net 2026 view: efavirenz market value is likely pressured by continued price competition even where volumes remain stable.

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Investment and licensing implications: what should stakeholders do now?

For brand holders or IP licensors

If any remaining formulation or process patents exist for specific marketed FDCs or pediatric forms, monetization is most viable through:

• Product-specific licensing for generic manufacturing where patent barriers still exist,
• Enforcement or settlement strategy focused on particular dosage forms/strengths.

For generics and FDC manufacturers

The most actionable diligence areas:

• Product-level patent mapping (FDC strength and dosage form),
• Bioequivalence and dissolution alignment with reference product requirements,
• Supply reliability and procurement compliance for tender schedules.

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Key Takeaways

• Efavirenz clinical activity is now dominated by formulation, bioequivalence, and special-population PK/tolerability studies rather than brand-funded Phase 3 efficacy.
• Market demand is projected to be flat to declining in most geographies, with durability driven by public-sector procurement and entrenched FDC supply.
• Core efavirenz compound exclusivity has little remaining impact; current IP barriers, if any, are mainly product/formulation-level.
• Competitive risk is primarily generic multi-source entry and substitution by integrase inhibitor regimens rather than new biologic threats.

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FAQs

1. Is efavirenz still recommended in HIV treatment guidelines in 2026?
2. How do neuropsychiatric adverse events affect efavirenz use and label updates across regions?
3. What are the main bioequivalence challenges for efavirenz fixed-dose combination tablets?
4. Which countries still rely most on efavirenz-based regimens through public procurement?
5. How does switching from efavirenz-based therapy to integrase inhibitor regimens impact virologic outcomes?

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References (APA)

1. FDA. (n.d.). Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration.
2. ClinicalTrials.gov. (n.d.). Search results for efavirenz (clinical studies). U.S. National Library of Medicine.
3. World Health Organization. (n.d.). Consolidated guidelines on HIV prevention, testing, treatment, service delivery. World Health Organization.