Know Cancer

or
forgot password

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


N/A
13 Years
N/A
Not Enrolling
Both
HIV Infections

Thank you

Trial Information

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


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.]

Inclusion Criteria


Inclusion Criteria

Concurrent Medication:

- Background AR nucleoside therapy is required, although background AR therapy may also
be no background therapy. However, the use of protease inhibitors is not recommended
as monotherapy unless there is no other alternative. Therefore, patients who are not
on AR treatment may be enrolled at the discretion of the clinician.

Allowed:

- Saquinavir.

Patients must have:

- Documented HIV infection.

- A CD4+ cell count <= 100/mm3 within 3 months prior to the study. [AS PER AMENDMENT
3/11/98: CD4+ cell count <= 200/mm3 any time prior to entry].

- Parental consent if patient is < 18 years old.

Prior Medication:

Allowed:

- Saquinavir (SQV).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Stage 2 or greater AIDS dementia complex.

- [AS PER AMENDMENT 10/2/97: Any acute disease or condition that would, in the
physician's judgement, contraindicate starting NFV or RTV.]

- Known hypersensitivity to RTV or any of its ingredients (for patients assigned to RTV
therapy).

Concurrent Medication:

Excluded:

- Concomitant use of protease inhibitors.

- Concomitant treatments that cannot be discontinued, and in the physician's judgement,
should not be taken with NFV or RTV.

AS PER AMENDMENT 10/2/97:

- For patients randomized to NFV:

- Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam,
ergot derivatives, amiodarone, quinidine, or rifampin.

For patients randomized to IDV:

- Concomitant therapy with terfenadine, astemizole, cisapride, triazolam, midazolam,
and rifampin.

Patients with any of the following prior symptoms are excluded:

AS PER AMENDMENT 10/2/97:

- History of clinically significant hypersensitivity reaction to any component of NFV
tablets (for patients assigned to NFV therapy).

Prior Medication:

Excluded:

- Prior use of protease inhibitors except SQV.

[AS PER AMENDMENT 10/2/97:

- Prior use of IDV for more than 4 weeks or other protease inhibitors (except SQV) for
any prior duration.]

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Principal Investigator

Perez G

Investigator Role:

Study Chair

Authority:

United States: Federal Government

Study ID:

CPCRA 042

NCT ID:

NCT00000859

Start Date:

Completion Date:

December 2001

Related Keywords:

  • HIV Infections
  • HIV-1
  • Drug Resistance
  • Drug Therapy, Combination
  • HIV Protease Inhibitors
  • CD4 Lymphocyte Count
  • Ritonavir
  • Indinavir
  • Disease Progression
  • RNA, Viral
  • Genotype
  • Nelfinavir
  • Anti-HIV Agents
  • Viral Load
  • HIV Infections
  • Acquired Immunodeficiency Syndrome

Name

Location

Community Consortium of San FranciscoSan Francisco, California  94110
Community Consortium / UCSFSan Francisco, California  94110
Denver CPCRA / Denver Public HlthDenver, Colorado  802044507
Denver Community Program for Clinical Research on AIDSDenver, Colorado  80204
Denver CPCRA / Denver Pub Hlth / Rocky Mt Cancer Ctr AuroraDenver, Colorado  802044507
Veterans Administration Med Ctr / Regional AIDS ProgramWashington, District of Columbia  20422
Washington Reg AIDS Prog / Dept of Infect DisWashington, District of Columbia  20422
Timothy A PriceWashington, District of Columbia  204220001
Infectious Disease Physicians / Northern VirginiaWashington, District of Columbia  204220001
AIDS Research Consortium of AtlantaAtlanta, Georgia  30308
AIDS Research Alliance - ChicagoChicago, Illinois  60657
Louisiana Comm AIDS Rsch Prog / Tulane Univ MedNew Orleans, Louisiana  70112
Louisiana Community AIDS Research ProgramNew Orleans, Louisiana  70112
Baltimore TRIALSBaltimore, Maryland  21201
Westat / NICHDRockville, Maryland  208503172
Wayne State Univ / Univ Hlth CtrDetroit, Michigan  48201
Henry Ford HospDetroit, Michigan  48202
Comprehensive AIDS Alliance of DetroitDetroit, Michigan  48201
Mercer Area Early Intervention ServicesCamden, New Jersey  081031438
Southern New Jersey AIDS Cln Trials / Dept of MedCamden, New Jersey  08103
Southern New Jersey AIDS Clinical TrialsCamden, New Jersey  08103
New Jersey Community Research InitiativeNewark, New Jersey  07103
North Jersey Community Research InitiativeNewark, New Jersey  071032842
Partners ResearchAlbuquerque, New Mexico  871315271
Partners in Research - New MexicoAlbuquerque, New Mexico  87131
Harlem AIDS Treatment Group / Harlem Hosp CtrNew York, New York  10037
Harlem AIDS Treatment GroupNew York, New York  10037
Portland Veterans Adm Med Ctr / Rsch & Education GrpPortland, Oregon  972109951
The Research and Education GroupPortland, Oregon  97210
Philadelphia FIGHTPhiladelphia, Pennsylvania  19107
Saint Joseph's HospPhiladelphia, Pennsylvania  19107
Richmond AIDS ConsortiumRichmond, Virginia  23298