A Comparison of Nelfinavir Plus Saquinavir Plus Delavirdine or 3TC/ZDV Versus Nelfinavir Plus 3TC/ZDV in HIV-Infected Patients
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Lamivudine/Zidovudine (Drug); Nelfinavir mesylate (Drug); Saquinavir (Drug); Delavirdine mesylate (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Fischl M, Study Chair
Bartlett J, Study Chair
Summary
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.
Clinical Details
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
Study design: Treatment, Open Label, Pharmacokinetics Study
Detailed description:
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
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
This study has been terminated.
Locations and Contacts
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Stanford Univ Med Ctr, Stanford, California 943055107, United States
Willow Clinic, Menlo Park, California 94025, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Emory Univ, Atlanta, Georgia 30308, United States
Queens Med Ctr, Honolulu, Hawaii 96816, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Louis A Weiss Memorial Hosp, Chicago, Illinois 60640, United States
Tulane Univ School of Medicine, New Orleans, Louisiana 70112, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Carolinas Med Ctr, Charlotte, North Carolina 28203, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Additional Information
Click here for more information about Saquinavir Click here for more information about Delavirdine mesylate Click here for more information about Nelfinavir mesylate Click here for more information about Lamivudine/Zidovudine
Last updated: June 23, 2005
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