A Comparison of Nelfinavir Plus Saquinavir Plus Delavirdine or 3TC/ZDV Versus Nelfinavir Plus 3TC/ZDV in HIV-Infected Patients
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Purpose
To compare the long-term virologic response to combination therapy with two protease inhibitors, i.e., nelfinavir (NFV) + saquinavir soft gel capsule (SQVsgc) and delavirdine (DLV) or combination lamivudine/zidovudine (3TC/ZDV, Combivir) versus NFV and 3TC/ZDV, in the proportion of patients demonstrating virologic success (< 500 copies/ml HIV RNA) at week 48, without prior virologic or clinical failure. To evaluate the safety and tolerance of combination protease inhibitors.
To evaluate the durability of virologic response as assessed by the Roche Ultra Sensitive assay (< 200 copies/ml) and culturable virus. To compare time to a confirmed virologic response (two consecutive plasma HIV RNA levels < 500 copies/ml) or to a confirmed treatment relapse following a confirmed virologic response across the treatment arms. To evaluate biologic phenotype (non-syncytium inducing versus syncytium inducing capacity) and the evolution and patterns of viral resistance among patients with confirmed treatment failures at or after weeks 16 to 24. To compare immunologic benefits, as measured by longitudinal CD4/CD8 cell count profiles. To evaluate the influence of baseline virologic and immunologic parameters on the magnitude and duration of plasma HIV RNA response. To compare virologic response between the two dose schedules of NFV and SQVsgc (bid vs tid) and between NFV and SQVsgc with either DLV or combination 3TC/ZDV. To evaluate compliance and exploratory population pharmacometrics.
Past studies have shown that combination therapies not only will result in better clinical outcomes but may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of HIV replication and alterations in resistance patterns. Both in vitro and in vivo studies suggest that triple-drug therapy may have an advantage over one- and two-drug regimens. Therefore, triple-drug therapy appears to be an important strategy in the treatment of HIV infection.
| Condition | Intervention | Phase |
|---|---|---|
|
HIV Infections |
Drug: Lamivudine/Zidovudine Drug: Nelfinavir mesylate Drug: Saquinavir Drug: Delavirdine mesylate |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Pharmacokinetics Study Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase II, Randomized, Controlled, Open-Label Trial of Combination Therapy With Nelfinavir (NFV) and Saquinavir (SQV)Sgc With Delavirdine (DLV) or 3TC/ZDV Versus Nelfinavir (NFV) and 3TC/ZDV in Subjects With HIV Infection and > 5,000 HIV RNA Copies/ML |
| Enrollment: | 0 |
Past studies have shown that combination therapies not only will result in better clinical outcomes but may prolong the effects of therapy. The enhanced effects seen with combination therapies are likely related to a greater suppression of HIV replication and alterations in resistance patterns. Both in vitro and in vivo studies suggest that triple-drug therapy may have an advantage over one- and two-drug regimens. Therefore, triple-drug therapy appears to be an important strategy in the treatment of HIV infection.
This is a Phase II, randomized, controlled, open-label trial of NFV + SQVsgc and either DLV or combined 3TC/ZDV versus NFV and combined 3TC/ZDV. Prior to randomization, patients are stratified by HIV RNA (above or below 65,000 copies/ml) and by prior antiretroviral therapy (no therapy vs any therapy). Patients (100 patients/arm) are then randomly assigned to one of four arms. Arm I receives NFV plus combination 3TC/ZDV. Arm II receives NFV plus SQVsgc plus combination 3TC/ZDV. Arm III receives NFV plus SQVsgc plus DLV. Arm IV receives NFV plus SQVsgc plus DLV. Treatment continues for 48 weeks following enrollment of the last patient. Response to treatment is assessed at week 16. Patients with confirmed plasma HIV RNA levels >= 500 copies/ml at week 16 whose plasma HIV RNA has decreased since study entry (day 0) may continue therapy and be reassessed at weeks 20 and 24. Patients considered treatment failures (i.e., 2 consecutive plasma HIV RNA levels >= 500 copies/ml at or after week 16) or who have relapsed may register to Step 2 treatment (addition of at least 2 new drugs to their prior treatment regimen), enroll in another ACTG protocol at time of failure, or seek the best available therapy while continuing to be followed for remainder of study.
Eligibility| Ages Eligible for Study: | 13 Years and older (Child, Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT00001094
| United States, California | |
| Willow Clinic | |
| Menlo Park, California, United States, 94025 | |
| Stanford Univ Med Ctr | |
| Stanford, California, United States, 943055107 | |
| United States, Colorado | |
| Univ of Colorado Health Sciences Ctr | |
| Denver, Colorado, United States, 80262 | |
| United States, Florida | |
| Univ of Miami School of Medicine | |
| Miami, Florida, United States, 331361013 | |
| United States, Georgia | |
| Emory Univ | |
| Atlanta, Georgia, United States, 30308 | |
| United States, Hawaii | |
| Queens Med Ctr | |
| Honolulu, Hawaii, United States, 96816 | |
| Univ of Hawaii | |
| Honolulu, Hawaii, United States, 96816 | |
| United States, Illinois | |
| Louis A Weiss Memorial Hosp | |
| Chicago, Illinois, United States, 60640 | |
| United States, Louisiana | |
| Tulane Univ School of Medicine | |
| New Orleans, Louisiana, United States, 70112 | |
| United States, New York | |
| SUNY / Erie County Med Ctr at Buffalo | |
| Buffalo, New York, United States, 14215 | |
| Bellevue Hosp / New York Univ Med Ctr | |
| New York, New York, United States, 10016 | |
| United States, North Carolina | |
| Carolinas Med Ctr | |
| Charlotte, North Carolina, United States, 28203 | |
| Moses H Cone Memorial Hosp | |
| Greensboro, North Carolina, United States, 27401 | |
| United States, Ohio | |
| Univ of Cincinnati | |
| Cincinnati, Ohio, United States, 452670405 | |
| Ohio State Univ Hosp Clinic | |
| Columbus, Ohio, United States, 432101228 | |
| United States, Texas | |
| Univ of Texas Galveston | |
| Galveston, Texas, United States, 775550435 | |
| Puerto Rico | |
| Univ of Puerto Rico | |
| San Juan, Puerto Rico, 009365067 | |
| Study Chair: | Fischl M | |
| Study Chair: | Bartlett J |
More Information
| ClinicalTrials.gov Identifier: | NCT00001094 History of Changes |
| Other Study ID Numbers: | ACTG 374 |
| Study First Received: | November 2, 1999 |
| Last Updated: | March 5, 2015 |
| Health Authority: | United States: Federal Government |
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
|
HIV-1 Drug Therapy, Combination Zidovudine Lamivudine RNA, Viral |
Saquinavir Delavirdine Anti-HIV Agents Nelfinavir |
Additional relevant MeSH terms:
|
Infection HIV Infections Acquired Immunodeficiency Syndrome Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Slow Virus Diseases Lamivudine Zidovudine Lamivudine, zidovudine drug combination |
Delavirdine Nelfinavir Saquinavir Reverse Transcriptase Inhibitors Nucleic Acid Synthesis Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Anti-HIV Agents Antimetabolites HIV Protease Inhibitors Protease Inhibitors Cytochrome P-450 CYP3A Inhibitors |
ClinicalTrials.gov processed this record on September 29, 2016