Clinical trial NCT00005915: A Comparison of Two Anti-HIV Treatment Plans
Official title: A Randomized Study of a Prescribed 4-Month Structured Treatment Interruption (STI) Followed by Initiation of a New Antiretroviral Regimen Versus Immediate Initiation of a New Antiretroviral Regimen in HIV-Infected Patients With Multidrug Resistant (MDR) Virus
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV-1
Drug Administration Schedule
Drug Resistance, Microbial
Disease Progression
Genotype
Phenotype
Drug Resistance, Multiple
Anti-HIV Agents
Treatment Experienced
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 480
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no

Brief summary: The purpose of this study is to compare 2 treatment plans to try to increase the effects of anti-HIV drugs in patients who are resistant to the drug effects.

Sometimes the increase in a patient's viral load (the level of HIV in the blood) can be slowed or stopped by taking anti-HIV drugs. This does not always happen. Sometimes anti-HIV drugs work at first but then stop working. When most of the usual anti-HIV drugs no longer seem to work, the virus is called multidrug-resistant (MDR). This study will compare 2 treatment plans to try to increase the effects of anti-HIV drugs in patients with MDR virus.

Detailed description: An increasing number of patients are developing multidrug-resistant (MDR) virus, as determined by genotypic antiretroviral resistance testing (GART), due to treatment failure to suppress viral replication after several rounds of combination antiretroviral therapy. The best therapeutic strategy for these patients is uncertain. Two strategies currently being used are (1) STI followed by a new antiretroviral regimen and (2) immediate initiation of a new antiretroviral regimen.

Patients are screened for the presence of MDR virus and a plasma HIV RNA level greater than 10,000 \[AS PER AMENDMENT 07/03/01: greater than 5,000\] copies/ml. Eligible patients attend a baseline visit \[AS PER AMENDMENT 07/03/01: and a subsequent randomization visit\] where the qualifying GART results are provided. Patients who consent to participate have phenotypic antiretroviral resistance testing (PART) done on a specimen from the same blood draw that was used for the GART evaluation. After PART results are available, patients are randomized \[AS PER AMENDMENT 07/03/01: If the predicted sensitivities are not available for some or all drugs included in the PART, the patient may still be randomized.\] to either a 4-month STI followed by a new antiretroviral regimen or an immediate new antiretroviral regimen. The antiretroviral regimens chosen are based on the patients' history and both GART and PART results. \[AS PER AMENDMENT 07/03/01: Additional GART and PART may be requested after at least 4 months of antiretroviral treatment.\] Patients have the follow-up data collection done at Months 1-8 and every 4 months thereafter. Changes in antiretroviral therapy, Grade 4 adverse experiences, progression of disease, and deaths are reported as they occur. Patients are seen for clinical management as often as deemed necessary. All patients are followed to a common closing date estimated to be 24 months after the last patient is randomized. Some patients may participate in a Point Mutation Substudy \[AS PER AMENDMENT 07/03/01: Plasma Point Mutation Substudy and PBMC Point Mutation Substudy\].

Eligibility criteria: Inclusion Criteria

Patients may be eligible if they:

* Have proof of MDR virus from a blood test.
* Have a viral load above 5,000 copies/ml from the same blood sample showing MDR virus.
* Intend to start a new anti-HIV treatment around the time of the study.
* Have been on a stable anti-HIV treatment between 14 days prior to the blood test mentioned above and when they are randomly assigned to a treatment.
* Are at least 13 years old (consent of parent or guardian required if under 18).
* (This protocol has been changed to reflect new criteria.)

Exclusion Criteria

Patients will not be eligible if they:

* Have received a vaccine or had an illness that might affect viral load within 14 days before the blood test showing MDR virus.
* Have received IL-2 within 4 months of the above-mentioned blood test or plan to take IL-2 during the study.
* Have an opportunistic (AIDS-related) infection requiring treatment.
* Are pregnant or breast-feeding.
* Are currently participating in CPCRA 057 (PIP study).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Community Consortium / UCSF
state: California
city: San francisco
country: United States
facility: Lawrence Goldyn, MD
state: California
city: Denver
country: United States
facility: Denver CPCRA / Denver Public Hlth
state: Colorado
city: Denver
country: United States
facility: Univ Hosp Infectious Disease
state: Colorado
city: New Haven
country: United States
facility: Yale U / New Haven Med Ctr / AIDS Clinical Trials Unit
state: Connecticut
city: Washington
country: United States
facility: Washington Reg AIDS Prog / Dept of Infect Dis
state: District of Columbia
city: Chicago
country: United States
facility: AIDS Research Alliance - Chicago
state: Illinois
city: New Orleans
country: United States
facility: Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
state: Louisiana
city: New Orleans
country: United States
facility: Our Lady of the Lake Regional Med Ctr
state: Louisiana
city: Detroit
country: United States
facility: Wayne State Univ - WSU/DMC / Univ Hlth Ctr
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hosp
state: Michigan
city: Camden
country: United States
facility: Southern New Jersey AIDS Clinical Trials
state: New Jersey
city: Newark
country: United States
facility: North Jersey Community Research Initiative
state: New Jersey
city: Bronx
country: United States
facility: Bronx-Lebanon Hosp Ctr
state: New York
city: New York
country: United States
facility: Harlem AIDS Treatment Grp / Harlem Hosp Ctr
state: New York
city: Portland
country: United States
facility: The Research and Education Group
state: Oregon
city: Philadelphia
country: United States
facility: Philadelphia FIGHT
state: Pennsylvania
city: Houston
country: United States
facility: Montrose Clinic
state: Texas
city: Houston
country: United States
facility: Houston Veterans Administration Med Ctr
state: Texas
city: Houston
country: United States
facility: Univ TX Health Science Ctr
state: Texas
city: Richmond
country: United States
facility: Richmond AIDS Consortium / Div of Infect Diseases
state: Virginia
Study officials:
name: Jody Lawrence
role: STUDY_CHAIR
References:
citation: Lawrence J, Mayers DL, Hullsiek KH, Collins G, Abrams DI, Reisler RB, Crane LR, Schmetter BS, Dionne TJ, Saldanha JM, Jones MC, Baxter JD; 064 Study Team of the Terry Beirn Community Programs for Clinical Research on AIDS. Structured treatment interruption in patients with multidrug-resistant human immunodeficiency virus. N Engl J Med. 2003 Aug 28;349(9):837-46. doi: 10.1056/NEJMoa035103.
citation: Anti-HIV agents. An attempt at treatment interruption--trial CPCRA 064. TreatmentUpdate. 2003 Aug-Sep;15(5):4-5. No abstract available.
citation: Lawrence J, Hullsiek KH, Thackeray LM, Abrams DI, Crane LR, Mayers DL, Jones MC, Saldanha JM, Schmetter BS, Baxter JD. Disadvantages of structured treatment interruption persist in patients with multidrug-resistant HIV-1: final results of the CPCRA 064 study. J Acquir Immune Defic Syndr. 2006 Oct 1;43(2):169-78. doi: 10.1097/01.qai.0000242450.74779.ee.
citation: Paquet AC, Baxter J, Weidler J, Lie Y, Lawrence J, Kim R, Bates M, Coakley E, Chappey C. Differences in reversion of resistance mutations to wild-type under structured treatment interruption and related increase in replication capacity. PLoS One. 2011 Jan 31;6(1):e14638. doi: 10.1371/journal.pone.0014638.