A Randomized Trial of the Efficacy and Safety of a Strategy of Starting With Nelfinavir Versus Ritonavir Added to Background Antiretroviral (AR) Nucleoside Therapy in HIV-Infected Individuals With CD4+ Cell Counts Less Than or Equal to 200/mm3
- Conditions
- HIV Infections
- Registration Number
- NCT00000859
- Brief Summary
To compare nelfinavir (NFV) with ritonavir (RTV) for delaying disease progression or death in HIV-infected patients with CD4+ cell counts less than 100 cells/mm3 \[AS PER AMENDMENT 3/11/98: less than or equal to 200 cells/mm3\]. To compare NFV with RTV for the development of adverse events and for rates of permanent discontinuation of study medication.
\[AS PER AMENDMENT 10/02/97: To compare by intention-to-treat analysis for disease progression, including death, the following two regimens: NFV plus background combination antiretroviral (AR) therapy followed by indinavir (IDV) or RTV in the event of significant intolerance; and RTV plus AR therapy followed by IDV, then NFV, in the event of significant intolerance.\] \[AS PER AMENDMENT 3/11/98: SUBSTUDY CPCRA 045: To determine the relative rates of emergence of HIV-1 resistance and to compare changes in plasma HIV RNA levels and CD4+ cell counts in a sample of patients with CD4+ cell counts \<= 200/mm3 who are enrolled in protocol CPCRA 042.\] AR therapy is rapidly becoming the standard of care for the treatment of HIV infection. AR therapy provides the best opportunity for maximizing viral suppression, reducing toxicity and delaying the emergence of resistant strains. The newest class of AR agents, the HIV protease inhibitors, exhibits the most potent anti-HIV effects described to date. This study will compare 2 protease inhibitors, NFV and RTV for efficacy and safety in a population with advanced HIV disease, who are taking various background nucleoside therapies.
- Detailed Description
AR therapy is rapidly becoming the standard of care for the treatment of HIV infection. AR therapy provides the best opportunity for maximizing viral suppression, reducing toxicity and delaying the emergence of resistant strains. The newest class of AR agents, the HIV protease inhibitors, exhibits the most potent anti-HIV effects described to date. This study will compare 2 protease inhibitors, NFV and RTV for efficacy and safety in a population with advanced HIV disease, who are taking various background nucleoside therapies.
Eligible patients will be randomized either to NFV plus background AR nucleoside therapy or to RTV plus background AR nucleoside therapy. Background AR therapy may also be no background therapy, although use of protease inhibitors as monotherapy is not recommended unless there is no alternative. Patients will be allowed to cross over to the alternate protease inhibitor if they reach a primary study endpoint. Data will be collected every 4 months.
\[AS PER AMENDMENT 10/2/97: Patients assigned to the NFV arm who develop a significant intolerance may switch to RTV or IDV; those assigned to the RTV arm who develop a significant intolerance are encouraged to switch to IDV (NFV allowed if IDV contraindicated). Switchover for intolerance is strongly discouraged during the first 4 weeks of follow-up. Patients initially assigned to NFV therapy who experience disease progression may switch to RTV; if RTV is not tolerated, patients may switch to IDV. Because of the cross-resistance between RTV and IDV, patients who progress on RTV should switch to NFV.\] \[AS PER AMENDMENT 12/15/98: Patients originally assigned to NFV who experience poor virologic control or disease progression should change to RTV or IDV or enroll in the PIP protocol (CPCRA 057). Conversely, patients originally assigned to RTV should change to NFV or enroll in the PIP protocol (such patients continue to be followed on this study). Because of cross-resistance between RTV and IDV, change from RTV to IDV is discouraged. Determination of poor virologic control or disease progression is at the discretion of the patient's clinician. Change in background antiretroviral therapy should occur at the same time that the protease inhibitor is changed for poor virologic control or progression; the choice of new background antiretroviral agents is at the discretion of the clinician.\] Randomization is stratified by clinical site.\] \[AS PER AMENDMENT 3/11/98: SUBSTUDY CPCRA 045: At least 600 patients (\>= 400 from CPCRA sites and \>= 200 from CTN sites) will be enrolled in the substudy. These patients will have a plasma sample collected for HIV RNA and genotypic resistance within 30 days prior to randomization, at the 1-month visit, and at the q-4-month study visits thereafter until the end of the study. CD4+ cell counts will be done at the 1-month visit and at the q-4-month study visits until the end of the study. A subset of patients will also have immunophenotyping of CD4+ and CD8+ cell TCR V-beta clones carried out before and during treatment. Another subset of patients at selected sites will have viral cultures performed for phenotypic drug sensitivity testing.
Initially, specimens for 50 randomly chosen patients in the group originally assigned RTV will be identified for resistance testing. Of this group, specimens for those who have received RTV/IDV for more than 1 month will be analyzed for genotypic resistance to obtain an estimate of the rate of resistance development and to estimate the risk of disease progression associated with resistance to RTV/ZDV. Based on these estimates, determination will be made of the total number of patients and specimens in both treatment groups in order to address the primary objective of comparing genotypic resistance in the two groups.\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1300
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (43)
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
AIDS Research Alliance - Chicago
🇺🇸Chicago, Illinois, United States
Baltimore TRIALS
🇺🇸Baltimore, Maryland, United States
Philadelphia FIGHT
🇺🇸Philadelphia, Pennsylvania, United States
New Jersey Community Research Initiative
🇺🇸Newark, New Jersey, United States
Sunnybrook Health Science Centre
🇨🇦Toronto, Ontario, Canada
Wellesley Hosp
🇨🇦Toronto, Ontario, Canada
Portland Veterans Adm Med Ctr / Rsch & Education Grp
🇺🇸Portland, Oregon, United States
Community Consortium / UCSF
🇺🇸San Francisco, California, United States
Denver CPCRA / Denver Pub Hlth / Rocky Mt Cancer Ctr Aurora
🇺🇸Denver, Colorado, United States
Denver Community Program for Clinical Research on AIDS
🇺🇸Denver, Colorado, United States
Denver CPCRA / Denver Public Hlth
🇺🇸Denver, Colorado, United States
Community Consortium of San Francisco
🇺🇸San Francisco, California, United States
Infectious Disease Physicians / Northern Virginia
🇺🇸Washington, District of Columbia, United States
Veterans Administration Med Ctr / Regional AIDS Program
🇺🇸Washington, District of Columbia, United States
Timothy A Price
🇺🇸Washington, District of Columbia, United States
Washington Reg AIDS Prog / Dept of Infect Dis
🇺🇸Washington, District of Columbia, United States
Louisiana Community AIDS Research Program
🇺🇸New Orleans, Louisiana, United States
Henry Ford Hosp
🇺🇸Detroit, Michigan, United States
Westat / NICHD
🇺🇸Rockville, Maryland, United States
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
🇺🇸New Orleans, Louisiana, United States
Wayne State Univ / Univ Hlth Ctr
🇺🇸Detroit, Michigan, United States
Comprehensive AIDS Alliance of Detroit
🇺🇸Detroit, Michigan, United States
Mercer Area Early Intervention Services
🇺🇸Camden, New Jersey, United States
Southern New Jersey AIDS Cln Trials / Dept of Med
🇺🇸Camden, New Jersey, United States
North Jersey Community Research Initiative
🇺🇸Newark, New Jersey, United States
Southern New Jersey AIDS Clinical Trials
🇺🇸Camden, New Jersey, United States
Partners Research
🇺🇸Albuquerque, New Mexico, United States
Partners in Research - New Mexico
🇺🇸Albuquerque, New Mexico, United States
The Research and Education Group
🇺🇸Portland, Oregon, United States
Harlem AIDS Treatment Group / Harlem Hosp Ctr
🇺🇸New York, New York, United States
Harlem AIDS Treatment Group
🇺🇸New York, New York, United States
Richmond AIDS Consortium
🇺🇸Richmond, Virginia, United States
Saint Joseph's Hosp
🇨🇦London, Ontario, Canada
QEII Health Science Centre
🇨🇦Halifax, Nova Scotia, Canada
Ottawa Gen Hosp
🇨🇦Ottawa, Ontario, Canada
Montreal Chest Institute
🇨🇦Montreal, Quebec, Canada
Toronto Gen Hosp
🇨🇦Toronto, Ontario, Canada
Hotel - Dieu de Montreal
🇨🇦Montreal, Quebec, Canada
SMBD-Jewish Gen Hosp
🇨🇦Montreal, Quebec, Canada
Centre De Recherche En Infectiologie
🇨🇦Ste-Foy, Quebec, Canada
Royal Univ Hosp
🇨🇦Saskatoon, Saskatchewan, Canada
Saint Paul's Hosp
🇨🇦Vancouver, British Columbia, Canada