CLINICAL TRIALS PROFILE FOR SUSTIVA

505(b)(2) Clinical Trials for Sustiva

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 Sustiva

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00001758 ↗	Continued Antiretroviral Therapy With Abacavir, Amprenavir and Efavirenz	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1997-11-01	This study will continue to treat and collect safety and efficacy data on patients who participated in Glaxo-Wellcome's multi-center study on combination therapy with abacavir, amprenavir and efavirenz (A Phase II Study Evaluating the Safety and Antiviral Activity of Combination Therapy with 1592U89, 141W94 and DMP 266 (Sustiva) in HIV-1 Infected Subjects with Detectable [greater than 400 Copies/mL] HIV-1 Plasma RNA Despite Treatment with a Protease Inhibitor-Containing Regimen). HIV-infected patients 18 years of age and older who participated in the above study at the NIH site may be eligible for the current study. Participants will be followed every 3 months with a general health evaluation and laboratory tests. This is a NIH study, and information will not be provided to Glaxo Wellcome
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.
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.
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.
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.
NCT00002235 ↗	A Study on the Safety and Effectiveness of Twice-Daily Nelfinavir Plus Twice-Daily Indinavir Plus Efavirenz in HIV-Positive Patients Who Have Never Taken Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or Protease Inhibitors	Completed	Agouron Pharmaceuticals	Phase 2	1969-12-31	Indinavir is usually taken three times a day. The purpose of this study is to see if it is safe and effective to take indinavir only twice a day plus nelfinavir (also taken twice a day) and efavirenz (taken once a day).
NCT00002235 ↗	A Study on the Safety and Effectiveness of Twice-Daily Nelfinavir Plus Twice-Daily Indinavir Plus Efavirenz in HIV-Positive Patients Who Have Never Taken Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) or Protease Inhibitors	Completed	Merck Sharp & Dohme Corp.	Phase 2	1969-12-31	Indinavir is usually taken three times a day. The purpose of this study is to see if it is safe and effective to take indinavir only twice a day plus nelfinavir (also taken twice a day) and efavirenz (taken once a day).

Clinical Trial Conditions for Sustiva

Condition Name

Condition Name for Sustiva
Intervention	Trials
HIV Infections	36
HIV	11
HIV Infection	8
Healthy	5

Condition MeSH

Condition MeSH for Sustiva
Intervention	Trials
HIV Infections	47
Acquired Immunodeficiency Syndrome	9
Infections	9
Infection	8

Clinical Trial Locations for Sustiva

Trials by Country

Trials by Country for Sustiva
Location	Trials
United States	145
Spain	29
Canada	8
Brazil	6
South Africa	6

Trials by US State

Trials by US State for Sustiva
Location	Trials
California	18
New York	11
District of Columbia	10
Texas	9
Florida	8

Clinical Trial Progress for Sustiva

Clinical Trial Phase

Clinical Trial Phase for Sustiva
Clinical Trial Phase	Trials
Phase 4	19
Phase 3	7
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for Sustiva
Clinical Trial Phase	Trials
Completed	55
Unknown status	4
Terminated	3

Clinical Trial Sponsors for Sustiva

Sponsor Name

Sponsor Name for Sustiva
Sponsor	Trials
Bristol-Myers Squibb	8
National Institute of Allergy and Infectious Diseases (NIAID)	6
Abbott	5

Sponsor Type

Sponsor Type for Sustiva
Sponsor	Trials
Other	76
Industry	44
NIH	15

Clinical Trials Update, Market Analysis, and Projection for SUSTIVA

Last updated: October 26, 2025

Introduction

SUSTIVA (efavirenz) remains a cornerstone in antiretroviral therapy (ART) for HIV-1 infection. First approved by the FDA in November 1998, SUSTIVA has been integral to HIV management worldwide. With a long-standing market presence, ongoing developments in HIV treatment, and emerging competition, it is vital to examine current clinical trial landscapes, market dynamics, and future projections. This analysis synthesizes recent clinical research, evaluates market trends, and offers strategic insights pertinent to stakeholders.

Clinical Trials Landscape for SUSTIVA

Recent Clinical Trial Updates

Over the past five years, numerous clinical trials have evaluated efavirenz’s role amidst evolving HIV therapy paradigms. Although the scope of new trials has diminished compared to earlier decades, ongoing research addresses safety, resistance patterns, and combination therapies:

• Long-term Safety Studies: Multiple post-market surveillance studies continue to affirm efavirenz's efficacy, focusing on neuropsychiatric adverse effects. A notable phase IV observational study (NCT03873274, ongoing) assesses neurocognitive outcomes in diverse populations.

• Resistance and Virologic Suppression: Trials such as the ARTEMIS study (NCT03451287) analyze resistance emergence patterns, especially in treatment-experienced patients. Findings emphasize the importance of adherence and resistance profiling.

• Comparative Efficacy in Different Populations: Trials investigating efavirenz within specialized cohorts, including pregnant women (NCT02736260), continue to evaluate safety and efficacy. The PROMISE study highlighted efavirenz’s safety profile during conception and pregnancy, aligning with current guidelines.

• Combination and Formulation Innovation: Research into fixed-dose combinations (FDCs) incorporating efavirenz, such as in generic formulations like Atripla, persists to improve adherence. New formulations targeting granular dosing or reduced neuropsychiatric effects are under investigation (e.g., NCT04908116).

Emerging Technologies and Innovations

While efavirenz remains a key component for many treatment regimens, pharmacogenomics is gaining prominence. Trials are evaluating genetic predictors of neuropsychiatric side effects, aiming to personalize therapy (e.g., NCT04567593). Additionally, long-acting injectable formulations, though not yet including efavirenz, may influence future use patterns, potentially diminishing reliance on daily oral efavirenz products.

Market Analysis of SUSTIVA

Current Market Overview

Despite being approved over two decades ago, efavirenz-based products like SUSTIVA retain significant global market share. The drug's affordability and widespread availability of generic formulations drive demand, particularly in low- and middle-income countries (LMICs).

• Global Revenue and Sales Trends: According to IQVIA data (2022), efavirenz products generated approximately $1.2 billion globally, with the majority attributable to generic versions. The decline from peak revenues (~$2 billion in 2010) correlates with the adoption of newer ART agents with improved tolerability.

• Market Share: EFV-based combination therapies, including Atripla and other FDCs, dominate initial ART regimens, especially in resource-limited settings. However, their market share is gradually waning as integrase inhibitors like dolutegravir gain popularity due to better tolerability profiles.

Competitive Landscape

Key competitors include:

• Dolutegravir-based Regimens: Globally preferred, owing to superior tolerability, fewer neuropsychiatric side effects, and higher barriers to resistance.
• Tenofovir and Emtricitabine Combinations: Often paired with integrase inhibitors, these are viewed as more patient-friendly options.
• Emerging Fixed-Dose Combinations: New formulations provide simplified dosing, further challenging efavirenz’s market dominance.

Market Challenges and Opportunities

• Tolerability Concerns: Neuropsychiatric adverse effects limit efavirenz’s appeal, especially in high-income markets.
• Patent Exclusivity and Generics: The loss of patent protections for efavirenz has driven price reductions, expanding access but compressing profit margins for branded SUSTIVA.
• Regulatory Dynamics: WHO guidelines (2019) favor integrase inhibitors as first-line therapy, reducing efavirenz’s role.

Geographical Market Divides

• Developing Countries: Demand remains strong due to cost-effectiveness; initiatives like PEPFAR and Global Fund heavily support efavirenz-based regimens.
• Developed Countries: Market penetration is limited; preference shifts toward newer agents with improved side effect profiles.

Market Projection and Future Outlook

Short-term Outlook (Next 2-3 Years)

The immediate future for SUSTIVA is characterized by a gradual decline attributable to:

• Increased adoption of integrase inhibitors (e.g., dolutegravir, bictegravir).
• Continued emphasis on regimen tolerability.
• Persistent use of generics, sustaining access in LMICs.

However, efavirenz remains relevant as a cost-effective cornerstone in many LMICs, especially where infrastructure for newer drugs is lacking.

Medium to Long-term Projection (3-10 Years)

• Declining but Sustained Market Share: The global HIV treatment landscape is shifting favorably toward integrase inhibitors, which are projected to comprise over 70% of first-line regimens by 2025 (UNAIDS, 2022).
• Niche and Special Use Cases: Efavirenz may see continued use in specific populations, such as pregnant women, where safety profiles are well-characterized.
• Potential New Indications and Formulations: Research into long-acting injectables or pharmacogenomic-guided therapy could facilitate tailored use, possibly prolonging efavirenz’s clinical relevance.

Market Revitalization Factors

• Price Reductions and Patent Expiry: The widespread availability of low-cost generics sustains access but limits profitability.
• Policy-driven Adoption: Some countries may sustain efavirenz in their national protocols due to logistics, cost considerations, and existing procurement frameworks.
• Innovation and Formulation Advancements: Development of neurotoxicity-reducing efavirenz formulations could improve tolerability and extend its market viability.

Strategic Implications for Stakeholders

• Pharmaceutical Companies: Focus on developing next-generation formulations, integrating pharmacogenomics, and expanding regional supply chains.
• Healthcare Providers: Balance cost-effectiveness with tolerability; individualize therapy based on patient comorbidities and genetic factors.
• Policy Makers: Maintain access strategies for generics while promoting adoption of newer agents where feasible.
• Investors: Expect moderate declines but recognize continued niche markets, especially in resource-limited settings.

Key Takeaways

• Existing Clinical Data: Long-term safety and resistance studies affirm efavirenz’s efficacy but highlight neuropsychiatric side effects as limitations.
• Market Shift: The global HIV treatment market is rapidly transitioning toward integrase inhibitor-based regimens, driven by enhanced safety and adherence.
• Regional Variability: Efavirenz remains critical in LMICs due to cost advantages, though high-income regions favor newer agents.
• Future Outlook: While overall market share will decline, efavirenz’s low cost and established safety profile suggest it will retain niche utility for several years, especially in areas with limited healthcare infrastructure.
• Innovation Opportunities: Developing neurotoxicity-mitigating formulations and personalized therapy based on pharmacogenetic insights could prolong relevance.

FAQs

1. Will SUSTIVA continue to be prescribed in the next decade?
Yes, particularly in resource-limited settings, due to its affordability and established efficacy. However, in high-income countries, its use is expected to decline as newer, better-tolerated agents become standard.

2. Are there ongoing clinical trials that could revive efavirenz’s role?
Current trials focus more on resistance, long-term safety, and combination formulations rather than reviving efavirenz as a first-line therapy. Innovations aiming to reduce neuropsychiatric effects may enhance its utility.

3. How does efavirenz’s safety profile compare with newer drugs?
Efavirenz is associated with neuropsychiatric adverse effects, including vivid dreams, depression, and cognitive disturbances. Newer agents like dolutegravir exhibit fewer side effects, influencing prescribing trends.

4. Can efavirenz be used during pregnancy?
Yes. Evidence supports efavirenz’s safety during pregnancy, which sustains its use in maternal HIV management, especially where alternatives are unavailable.

5. What are the main market drivers for efavirenz now?
Cost-effectiveness, established clinical profile, availability of generics, and policy frameworks in LMICs are primary drivers, despite emerging competition from newer regimens.

Conclusion

SUSTIVA’s clinical utility and market presence have persisted through decades, rooted in cost-effective efficacy. However, evolving clinical evidence, patent expirations, and shifting treatment guidelines forecast a gradual decline in its market share. Despite this, it maintains vital importance in global HIV programs, especially within economically constrained regions. Future strategies should emphasize formulation innovation, pharmacogenetic integration, and targeted applications to sustain relevance amid rapid advancements in HIV therapy.

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Sources
[1] UNAIDS. Global HIV & AIDS statistics — 2022 fact sheet.
[2] IQVIA. Global HIV marketplace report, 2022.
[3] World Health Organization. Consolidated guidelines on HIV prevention, diagnosis, treatment, service delivery — 2019.
[4] ClinicalTrials.gov entries related to efavirenz studies.