CLINICAL TRIALS PROFILE FOR EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

All Clinical Trials for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00084136 ↗	Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 4	2005-05-01	This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.
NCT00084136 ↗	Prospective Evaluation of Anti-retroviral Combinations for Treatment Naive, HIV Infected Persons in Resource-limited Settings	Completed	AIDS Clinical Trials Group	Phase 4	2005-05-01	This study compared 3 different three-drug combinations in HIV infected individuals starting their first HIV treatment regimens. Participants were recruited from resource-limited areas in Africa, Asia, South America, Haiti, and also from the United States. The study hypothesis was each of the once daily combinations (PI based, or NNRTI based) would not have inferior efficacy compared to the twice daily NNRTI based combination.
NCT00112047 ↗	Tenofovir Disoproxil Fumarate/Emtricitabine/Efavirenz Versus Combivir/Efavirenz in Antiretroviral-Naive HIV-1 Infected Subjects	Completed	Gilead Sciences	Phase 3	2003-07-01	The purpose of Study GS-01-934 was to assess the efficacy and safety of two simplified antiretroviral treatment (ART) regimens in ART-naive, human immunodeficiency virus, type 1 (HIV-1) infected participants. The primary objective of the study was to assess noninferiority of emtricitabine (FTC) and tenofovir disoproxil fumarate (tenofovir DF; TDF) in combination with efavirenz (EFV) relative to Combivir (CBV) in combination with EFV in the treatment of HIV-1 infected ART-naive participants, determined by the achievement and maintenance of confirmed HIV-1 ribonucleic acid (RNA) < 400 copies/mL (c/mL) through Week 48, as defined by the United States (US) Food and Drug Administration (FDA) time-to-loss-of-virologic-response (TLOVR) algorithm.
NCT00039741 ↗	Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children	Completed	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	Phase 2/Phase 3	2002-08-01	Little is known about what treatment combinations are best for HIV infected children. This study examined the long-term effectiveness of different anti-HIV drug combinations in children and strategies for switching treatment if the first treatment does not work. The study enrolled children who had not previously taken anti-HIV medication. Participants in this study were recruited in the United States, South America and Europe. Some European children may also enroll in a substudy that will observe changes in body fat in children taking anti-HIV medications.
NCT00039741 ↗	Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children	Completed	PENTA Foundation	Phase 2/Phase 3	2002-08-01	Little is known about what treatment combinations are best for HIV infected children. This study examined the long-term effectiveness of different anti-HIV drug combinations in children and strategies for switching treatment if the first treatment does not work. The study enrolled children who had not previously taken anti-HIV medication. Participants in this study were recruited in the United States, South America and Europe. Some European children may also enroll in a substudy that will observe changes in body fat in children taking anti-HIV medications.
NCT00039741 ↗	Anti-HIV Drug Regimens and Treatment-Switching Guidelines in HIV Infected Children	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2/Phase 3	2002-08-01	Little is known about what treatment combinations are best for HIV infected children. This study examined the long-term effectiveness of different anti-HIV drug combinations in children and strategies for switching treatment if the first treatment does not work. The study enrolled children who had not previously taken anti-HIV medication. Participants in this study were recruited in the United States, South America and Europe. Some European children may also enroll in a substudy that will observe changes in body fat in children taking anti-HIV medications.
NCT00087464 ↗	Three Month Course of Anti-HIV Medications for People Recently Infected With HIV	Withdrawn	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	Short-term therapy may reduce the amount of HIV in the blood of adults recently infected with HIV. The purpose of this study is to see whether it is better for people to take a short course of anti-HIV drugs when they are first infected or if it is better to wait until the HIV infection causes health problems before taking anti-HIV drugs.

Clinical Trial Conditions for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

Condition Name

Condition Name for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Intervention	Trials
HIV Infections	18
HIV-1 Infection	7
HIV	5
HIV Infection	3

Condition MeSH

Condition MeSH for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Intervention	Trials
HIV Infections	26
Acquired Immunodeficiency Syndrome	9
Immunologic Deficiency Syndromes	6
Infection	3

Clinical Trial Locations for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

Trials by Country

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Trials by Country for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Location	Trials
United States	232
Canada	16
Germany	11
South Africa	10
United Kingdom	9

Trials by US State

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−

Trials by US State for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Location	Trials
California	15
Florida	13
Illinois	12
North Carolina	12
New York	12

Clinical Trial Progress for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

Clinical Trial Phase

Clinical Trial Phase for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Clinical Trial Phase	Trials
Phase 4	8
Phase 3	16
Phase 2/Phase 3	1

Clinical Trial Status

Clinical Trial Status for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Clinical Trial Phase	Trials
Completed	29
Withdrawn	3
Unknown status	2

Clinical Trial Sponsors for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE

Sponsor Name

Sponsor Name for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Sponsor	Trials
Gilead Sciences	15
National Institute of Allergy and Infectious Diseases (NIAID)	11
AIDS Clinical Trials Group	5

Sponsor Type

Sponsor Type for EFAVIRENZ; EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE
Sponsor	Trials
Industry	34
Other	25
NIH	14

Efavirenz, Emtricitabine, and Tenofovir Disoproxil Fumarate: Clinical Trials, Market Analysis, and Projections

Introduction

The combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate, commonly known as Atripla, has been a cornerstone in the treatment of HIV-1 infection since its approval in 2006. This article will delve into the clinical trials, market analysis, and future projections for this drug combination.

Clinical Trials and Efficacy

Initial Approval and Study 934

Atripla was licensed based on data from Study 934, which compared the combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate to a combination of efavirenz, zidovudine, and lamivudine. The study showed that more patients in the emtricitabine and tenofovir arm achieved viral loads below 400 copies/ml after 48 weeks, largely due to fewer discontinuations due to drug side effects[4].

Long-Term Efficacy and Safety

The ADVANCE trial, although not specifically focused on Atripla, provides valuable insights into the long-term efficacy and safety of similar regimens. This trial compared different first-line antiretroviral therapies, including those containing tenofovir disoproxil fumarate (TDF) and efavirenz (EFV), over a 192-week period. The results highlighted the potency and safety of these regimens but also noted substantial weight gain associated with dolutegravir-containing regimens, which could be a consideration for long-term treatment[1].

Switching Studies

A study on switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to rilpivirine, emtricitabine, and tenofovir alafenamide (TAF) showed that viral suppression was maintained in both groups, with the TAF regimen demonstrating non-inferiority. This study also highlighted the safety and tolerability of switching to the TAF-based regimen, which may offer reduced bone and renal risks compared to TDF[3].

Market Analysis

Current Market Landscape

The HIV treatment market is dominated by a few key players, with Gilead Sciences being the leading company. Atripla, although still used, has seen a decline in demand, leading to its discontinuation as a branded product by the end of 2021. However, numerous generic versions of Atripla are available, which continue to be prescribed[4][5].

Competitive Products

The market has seen the emergence of newer, more convenient, and potentially safer treatments. For example, Gilead's Biktarvy (bictegravir/emtricitabine/TAF) and ViiV Healthcare's Juluca (dolutegravir/rilpivirine) have gained significant traction. These newer regimens offer improved safety profiles and reduced toxicity, which are attractive to both patients and healthcare providers[2][5].

Market Projections

The global HIV treatment market is expected to grow modestly, driven by the introduction of novel integrase inhibitor (INI) and protease inhibitor (PI) based single-tablet regimens. By 2025, the market is projected to reach $22.5 billion, with companies like Gilead Sciences, ViiV Healthcare, and Janssen competing for market share[2][5].

Safety and Tolerability

Common Side Effects

The combination of efavirenz, emtricitabine, and tenofovir disoproxil fumarate is associated with several common side effects, including increases in lipid levels, liver enzymes, pancreatic enzymes, blood glucose, phosphate, and creatine kinase. It is contraindicated in patients with impaired kidney function (creatine clearance less than 50ml/min)[4].

Drug Interactions

Efavirenz, a component of Atripla, interacts with many drugs, requiring careful management and potential dosing adjustments. This complexity can make the regimen less favorable compared to newer, simpler regimens[4].

Resistance and Cross-Resistance

Viral rebound or lack of viral suppression on the efavirenz/emtricitabine/TDF combination most frequently leads to resistance to efavirenz and cross-resistance to other non-nucleoside reverse transcriptase inhibitors (NNRTIs). Resistance to emtricitabine and TDF is rare but can occur[4].

Pregnancy and Pediatric Use

Efavirenz is not recommended during the first trimester of pregnancy due to potential teratogenic effects. The combination is not approved for use in children or adolescents under 18 years of age[4].

Future Projections

Generic Competition

The availability of generic versions of Atripla will continue to impact its market share. As more generics enter the market, the pricing pressure on branded products will increase, potentially reducing the overall revenue from this combination[4].

Newer Therapies

The emergence of newer, more convenient, and safer therapies will likely continue to erode the market share of Atripla. Regimens like Biktarvy and Juluca, with their improved safety profiles and reduced toxicity, are expected to dominate the market in the coming years[2][5].

Pipeline Assessment

The HIV treatment pipeline includes several promising drugs in clinical development, such as bictegravir/emtricitabine/TAF, dolutegravir/lamivudine, and cabotegravir/rilpivirine. These drugs are expected to further shift the market landscape away from older combinations like Atripla[2].

Key Takeaways

• Efficacy and Safety: Atripla has been shown to be effective in clinical trials, but long-term use is associated with side effects and potential resistance issues.
• Market Trends: The HIV market is shifting towards newer, safer, and more convenient treatments, reducing the demand for Atripla.
• Generic Impact: Generic versions of Atripla will continue to affect its market share and pricing.
• Future Competition: Newer therapies with improved safety profiles will dominate the market, further reducing Atripla's relevance.

FAQs

Q: What is the composition of Atripla?

A: Atripla is a fixed-dose combination tablet containing 600mg efavirenz, 200mg emtricitabine, and 245mg tenofovir disoproxil fumarate[4].

Q: What are the common side effects of Atripla?

A: Common side effects include increases in lipid levels, liver enzymes, pancreatic enzymes, blood glucose, phosphate, and creatine kinase. It is also associated with impaired kidney function and drug interactions[4].

Q: Is Atripla approved for use in children?

A: No, the efavirenz/emtricitabine/TDF combination is not approved for use in children or adolescents under 18 years of age[4].

Q: What are the newer alternatives to Atripla?

A: Newer alternatives include Biktarvy (bictegravir/emtricitabine/TAF) and Juluca (dolutegravir/rilpivirine), which offer improved safety profiles and reduced toxicity[2][5].

Q: How is the market for HIV treatments projected to grow?

A: The global HIV treatment market is expected to grow to $22.5 billion by 2025, driven by the introduction of novel integrase inhibitor and protease inhibitor based single-tablet regimens[2][5].

Sources

1. ADVANCE Trial: Final 192-Week Efficacy and Safety Results of the ADVANCE Trial. Oxford University Press, 2024.
2. GlobalData Report: Global Drug Forecast and Market Analysis to 2025. GlobalData, 2017.
3. Switching Study: Switching from efavirenz, emtricitabine, and tenofovir disoproxil fumarate to rilpivirine, emtricitabine, and tenofovir alafenamide. PubMed, 2017.
4. Aidsmap: Efavirenz/emtricitabine/tenofovir disoproxil fumarate. Aidsmap, 2024.
5. BioSpace: Companies Fight for Growing Share of HIV Market. BioSpace, 2018.