CLINICAL TRIALS PROFILE FOR LAMIVUDINE AND ZIDOVUDINE

All Clinical Trials for LAMIVUDINE AND ZIDOVUDINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000831 ↗	Virologic Responses To New Nucleoside Regimens After Prolonged ZDV or ddI Monotherapy	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To elucidate the relationship between virologic risk factors and immunologic and clinical progression in patients receiving monotherapy in protocol ACTG 175, and to compare new treatment regimens with combinations of reverse transcriptase inhibitors in long-term recipients of monotherapy. Specifically, to determine, in patients who have been taking zidovudine (AZT) alone for a long time, whether it is beneficial to add lamivudine (3TC) to AZT or to switch to d4T alone, and also to determine, in patients who have been taking didanosine (ddI) alone for a long time, whether it is beneficial to add AZT or AZT/3TC to ddI. Characteristics of virus replication, pathogenicity, and resistance are thought to determine the durability of virologic and clinical response to nucleoside reverse transcriptase inhibitors. Previous results of ACTG 175 suggest that either a switch to ddI or addition of ddI in patients receiving AZT results in better clinical, virologic, and CD4 cell response compared to continuation of AZT alone.
NCT00000834 ↗	A Phase I Study of Methotrexate for HIV Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To determine the safety and tolerance of methotrexate in HIV-infected patients. To determine the dose effective in modulating key markers of immune activation. To determine a dose suitable for Phase II or III evaluation in HIV-infected patients. In HIV infection, complete immunological clearance of the foreign antigen does not occur, resulting in chronic immune activation. Because chronic immune activation may contribute to disease progression in HIV infection, immunomodulators may have therapeutic value in early HIV disease prior to development of opportunistic infections. The clinical benefits of methotrexate appear to derive from an anti-inflammatory effect; thus, it may reduce the state of chronic immune activation.
NCT00000838 ↗	Antiviral Activity of and Resistance to Lamivudine in Combination With Zidovudine, Stavudine, or Didanosine	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the efficacy, safety, and pharmacokinetics of lamivudine (3TC) combined with zidovudine (AZT), stavudine (d4T), or didanosine (ddI) in comparison with d4T or ddI monotherapy in HIV-infected patients with no prior nucleoside therapy. 3TC may be uniquely effective in combination with AZT due to the interaction of AZT and 3TC resistance mutations. One explanation is that the M184V mutation, which confers resistance to 3TC, suppresses AZT resistance. This benefit of 3TC may not extend to combination therapy with other nucleoside analogs.
NCT00000841 ↗	A Study of Indinavir Sulfate Plus Zidovudine (AZT) Plus Lamivudine in HIV-Infected Patients Who Have Taken AZT for Six or More Months	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 3	1969-12-31	To determine the clinical efficacy of indinavir sulfate or placebo in combination with zidovudine ( AZT ) and lamivudine ( 3TC ) in AIDS patients. Protease inhibitors such as indinavir sulfate may be effective in patients with advanced HIV disease who have received prior AZT therapy. Since studies suggest that triple drug therapy may have an advantage over both monotherapy and two drug therapy, the combination of indinavir sulfate with AZT and 3TC should be evaluated.
NCT00000861 ↗	The Addition of Indinavir to Anti-HIV Treatment in HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	The purpose of this study is to evaluate the effect of immediate versus deferred indinavir (IDV) in addition to background therapy on disease progression or death in patients with CD4+ cell counts between 200 and 500 cells/mm3 and plasma HIV RNA levels >= 10,000 copies/ml. This study aims to examine two management strategies, immediate versus deferred IDV therapy, for their clinical effects in the context of background antiretroviral (AR) therapy, given according to current clinical practice. There is an urgent need to identify the optimal use of IDV in patient management, since clinical endpoint studies have not been completed in the United States. Since there is little information about the long term durability of clinical effects, and even less information about the timing of the initiation of protease inhibitor therapy, exploring the disease progression and survival impact of immediate versus delayed use of IDV will yield important information to guide clinical decision making for this group of patients.
NCT00000865 ↗	The Safety and Effects of 1592U89 Used Alone or in Combination With Other Anti-HIV Drugs in HIV-Infected Infants and Children	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	1969-12-31	To assess the steady state pharmacokinetic features, tolerance, and safety of orally administered 1592U89, given alone or in combination with other antiretroviral medications, in HIV infected infants and children. To establish doses of 1592U89 appropriate for future pediatric Phase II/III clinical trials. On the basis of the preclinical and clinical studies, 1592U89 appears to be a promising agent for treatment of HIV infection in children, either as an alternative to currently employed agents, or in combination therapy regimens. A liquid formulation of the drug is available; thus concurrent development of 1592U89 for children and adults is possible.

Clinical Trial Conditions for LAMIVUDINE AND ZIDOVUDINE

Condition Name

Condition Name for LAMIVUDINE AND ZIDOVUDINE
Intervention	Trials
HIV Infections	133
HIV	20
HIV Infection	10
Tuberculosis	6

Condition MeSH

Condition MeSH for LAMIVUDINE AND ZIDOVUDINE
Intervention	Trials
HIV Infections	152
Infections	34
Acquired Immunodeficiency Syndrome	33
Infection	28

Clinical Trial Locations for LAMIVUDINE AND ZIDOVUDINE

Trials by Country

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−

Trials by Country for LAMIVUDINE AND ZIDOVUDINE
Location	Trials
Puerto Rico	41
Canada	40
Spain	34
South Africa	31
China	18

Trials by US State

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−

Trials by US State for LAMIVUDINE AND ZIDOVUDINE
Location	Trials
California	84
New York	68
Illinois	59
Florida	58
North Carolina	53

Clinical Trial Progress for LAMIVUDINE AND ZIDOVUDINE

Clinical Trial Phase

Clinical Trial Phase for LAMIVUDINE AND ZIDOVUDINE
Clinical Trial Phase	Trials
Phase 4	37
Phase 3	47
Phase 2/Phase 3	8

Clinical Trial Status

Clinical Trial Status for LAMIVUDINE AND ZIDOVUDINE
Clinical Trial Phase	Trials
Completed	159
Unknown status	14
Terminated	7

Clinical Trial Sponsors for LAMIVUDINE AND ZIDOVUDINE

Sponsor Name

Sponsor Name for LAMIVUDINE AND ZIDOVUDINE
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	69
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	21
Glaxo Wellcome	16

Sponsor Type

Sponsor Type for LAMIVUDINE AND ZIDOVUDINE
Sponsor	Trials
Other	162
NIH	97
Industry	97

Lamivudine and Zidovudine: Clinical Trials, Market Analysis, and Projections

Introduction

Lamivudine and zidovudine are two nucleoside reverse transcriptase inhibitors (NRTIs) that have been cornerstone components of antiretroviral therapy (ART) for HIV infection. This article provides an update on the clinical trials involving these drugs, analyzes the current market, and projects future trends.

Clinical Trials Overview

Efficacy and Safety Comparisons

Clinical trials have extensively evaluated the efficacy and safety of lamivudine and zidovudine, often in combination with other antiretroviral drugs. A notable study compared abacavir with zidovudine plus lamivudine and efavirenz in antiretroviral-naive patients. This multicenter, randomized, double-blind noninferiority trial found that the abacavir regimen was noninferior to the zidovudine regimen in achieving viral suppression[1].

Combination Therapies

Another significant trial compared combinations of zidovudine, didanosine, and nevirapine. This randomized, double-blind trial demonstrated that triple drug therapy with zidovudine, didanosine, and nevirapine led to a substantially greater decrease in plasma viral load and an increase in CD4 cell count compared to two-drug regimens[4].

Resistance and Cross-Resistance

Studies have also focused on the development of resistance to lamivudine and zidovudine. Genotypic analysis has shown that resistance to these drugs is associated with specific amino acid substitutions in the HIV-1 reverse transcriptase. Cross-resistance among NRTIs, including lamivudine and zidovudine, has been observed, highlighting the need for careful selection of combination therapies[2].

Market Analysis

Global Market Size and Growth

The global HIV clinical trials market, which includes trials involving lamivudine and zidovudine, is expected to grow significantly. In 2024, the market size was estimated at USD 1.30 billion and is projected to reach USD 2.42 billion by 2034, with the Asia Pacific region anticipated to register the fastest CAGR of 8.7% during the forecast period[3].

Regional Dominance

North America currently dominates the market with a revenue share of over 45.0% in 2024, driven by the multitude of HIV clinical trials conducted in the region, increased awareness, and substantial investments in R&D by pharmaceutical companies and government institutions[3].

Key Players and Sponsors

Major pharmaceutical companies such as Gilead Sciences, Janssen Pharmaceuticals, and ViiV Healthcare are significant investors and contributors to HIV clinical trials. The National Institutes of Health (NIH), particularly through the National Institute of Allergy and Infectious Diseases (NIAID), also plays a crucial role in funding research endeavors[3].

Market Segments and Trends

By Phase

The HIV clinical trials market is segmented by phase, with Phase I holding the largest revenue share, focusing on the evaluation of drug safety, efficacy, and toxicity. Phase II is expected to register a significant CAGR, driven by increased investments in R&D and the integration of AI and machine learning tools for personalized care[3].

By Study Design

Interventional studies dominate the market, helping in the assessment of adaptable, economical, and prophylactic measures to treat HIV infections. These studies also assist in developing optimization strategies and estimating the impact of treatment on individuals[3].

Future Projections and Innovations

Integration of AI and Machine Learning

The future of HIV clinical trials, including those involving lamivudine and zidovudine, is likely to be shaped by the integration of AI and machine learning. These technologies can identify patterns and trends in patient data, leading to long-term beneficial outcomes and personalized care[3].

Development of New Regimens

Recent studies, such as the DOLCE study by ViiV Healthcare, have shown that two-drug regimens like dolutegravir/lamivudine can achieve similar results to three-drug regimens for viral suppression in advanced HIV populations. Such innovations are expected to continue, offering more efficient and less toxic treatment options[3].

Safety and Adverse Effects

Hematologic Toxicity

Zidovudine has been associated with hematologic toxicity, including neutropenia and severe anemia, particularly in patients with advanced HIV disease. Prolonged use of zidovudine has also been linked to symptomatic myopathy and lactic acidosis with severe hepatomegaly and steatosis[2].

Hepatitis B Co-infection

Patients co-infected with hepatitis B virus (HBV) and HIV who discontinue lamivudine are at risk of severe acute exacerbations of hepatitis B. Close monitoring of hepatic function is recommended in these cases[2].

Key Takeaways

• Clinical Efficacy: Lamivudine and zidovudine, often in combination with other antiretrovirals, have been shown to be effective in suppressing HIV-1 RNA and increasing CD4 cell counts.
• Market Growth: The global HIV clinical trials market is expected to grow significantly, driven by increasing R&D investments and the integration of AI and machine learning.
• Regional Trends: North America dominates the market, but the Asia Pacific region is expected to grow at the fastest CAGR.
• Safety Considerations: Patients must be monitored for hematologic toxicity, myopathy, and hepatitis B exacerbations when using these drugs.
• Future Innovations: New regimens and the use of AI and machine learning are expected to enhance treatment outcomes and personalize care.

FAQs

Q: What are the common side effects of lamivudine and zidovudine?

A: Common side effects include hematologic toxicity such as neutropenia and anemia, symptomatic myopathy, and lactic acidosis with severe hepatomegaly and steatosis.

Q: How effective are lamivudine and zidovudine in combination therapy?

A: Studies have shown that combination therapy with lamivudine and zidovudine, along with other antiretrovirals, can significantly reduce plasma HIV-1 RNA levels and increase CD4 cell counts.

Q: What is the current market size of the HIV clinical trials involving lamivudine and zidovudine?

A: The global HIV clinical trials market was estimated at USD 1.30 billion in 2024 and is projected to reach USD 2.42 billion by 2034.

Q: Which region is expected to grow the fastest in the HIV clinical trials market?

A: The Asia Pacific region is anticipated to register the fastest CAGR of 8.7% during the forecast period.

Q: How are AI and machine learning impacting HIV clinical trials?

A: AI and machine learning are being integrated to identify patterns and trends in patient data, leading to personalized care and better treatment outcomes.

Sources

1. Abacavir versus Zidovudine Combined with Lamivudine and Efavirenz for HIV Infection in Antiretroviral-Naive Adults: A Randomized Equivalence Trial. Clinical Infectious Diseases, Volume 39, Issue 7, 1 October 2004.
2. Lamivudine/Nevirapine/Zidovudine Tablets. FDA, [PDF].
3. HIV Clinical Trials Market Size Expected to Hit USD 2.42 Billion by 2034. Biospace, 3 December 2024.
4. A Randomized, Double-blind Trial Comparing Combinations of Nevirapine, Didanosine, and Zidovudine for HIV-1 Infection. JAMA, 1997.