Clinical trial NCT00000939: A Study to Compare the Effectiveness of Different Anti-HIV Drug Regimens in Keeping Levels of HIV in the Blood as Low as Possible
Official title: Phase II Randomized, Open-Label Study of Maintenance of HIV RNA Suppression After Switching to ddI/d4T/HU vs. ddI/d4T/EFV vs. Continuing the Pre-Entry Protease Inhibitor Regimen
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: Didanosine
Drug Therapy, Combination
Stavudine
HIV Protease Inhibitors
Hydroxyurea
RNA, Viral
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load
efavirenz
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 150
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: This study will look at different anti-HIV drug regimens to see which works best to keep the level of HIV (viral load) in the blood as low as possible during maintenance therapy. You will be assigned randomly (like tossing a coin) to 1 of 3 groups:

Group 1: Didanosine plus stavudine plus hydroxyurea (ddI/d4T/HU). Group 2: Didanosine plus stavudine plus efavirenz (ddI/d4T/EFV). Group 3: This group of patients will remain on their current drug regimens. This study will last approximately 3 years; you will receive study medications for the duration of the study.

Anti-HIV drug regimens that include protease inhibitors (PIs) are very good at lowering viral load. However, some patients have a rise in HIV levels while on PI maintenance. It may be possible to keep HIV levels low using another class of drugs for maintenance that are easier to take and less expensive than PIs. If viral load increases while a patient is taking this second group of drugs, it may be possible to restart the PI drug regimen and again decrease HIV levels.

Detailed description: Combination antiretroviral therapies using protease inhibitors (PIs) are capable of suppressing plasma HIV RNA to undetectable levels. However, approximately 10% of patients who achieve undetectable viral loads will experience a detectable rise in HIV RNA each year. When HIV replication has been suppressed to very low levels, it may be possible to consolidate antiretroviral therapy into a simpler and potentially less toxic "maintenance" regimen without a PI. Such a regimen would ideally be potent enough to continue to maintain viral suppression but use agents that are better tolerated, more easily salvaged, less expensive, and/or more convenient than PI-containing regimens. Subsequent rises in HIV viremia with non-PI maintenance regimens may respond to resumption of the pre-maintenance PI-containing regimen, extending the use of the potent PI class.

Patients are randomized 1:1:1 to treatment with ddI/d4T/HU (Arm A) versus ddI/d4T/EFV (Arm B) versus continuation of the pre-entry PI-containing regimen (Arm C). Viral load is measured at Weeks 1, 2, 4, 8, 12, 16, 20, and 24, then every 8 weeks for up to 3 years. Upon virologic failure (plasma HIV RNA greater than or equal to 200 copies/ml), or drug intolerance, patients on the maintenance regimens (Arms A and B) restart their pre-entry PI-containing regimen. Patients on Arm C are managed according to best medical judgment of their primary care provider in the event of virologic failure.

Eligibility criteria: Inclusion Criteria

You may be eligible for this study if you:

* Are at least 13 years old (need consent if under 18).
* Are HIV-positive.
* Are taking your first anti-HIV drug regimen, which must include a PI and at least one NRTI (nucleoside reverse transcriptase inhibitor) and have been on this regimen for at least 12 months.
* Have a viral load less than 400 copies/ml for at least 12 months prior to study entry, and have a viral load less than 50 copies/ml within 60 days of study entry.
* Have a CD4 cell count of at least 200 cells/mm3 within 60 days of study entry.
* Are willing to go back on the drugs you are currently on, if necessary.
* Are willing to use effective methods of birth control during the study and for 3 months after.

Exclusion Criteria

You will not be eligible for this study if you:

* Have taken ddI, d4T, or HU for more than 2 weeks.
* Have taken any NNRTI (non-nucleoside reverse transcriptase inhibitor) for more than 7 days.
* Have ever taken EFV.
* Have received an HIV vaccine within 30 days prior to study entry.
* Have an AIDS-related cancer that requires chemotherapy.
* Have or have had pancreatic disease.
* Are being treated for a significant illness.
* Abuse drugs or alcohol.
* Are pregnant or breast-feeding.
* Are allergic to any study drugs.
* Have received certain medications.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Menlo Park
country: United States
facility: Willow Clinic
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med Ctr / AIDS Community Rsch Consortium
state: California
city: Stanford
country: United States
facility: San Mateo AIDS Program / Stanford Univ
state: California
city: Stanford
country: United States
facility: Stanford Univ Med Ctr
state: California
city: Miami
country: United States
facility: Univ of Miami School of Medicine
state: Florida
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Division of Inf Diseases/ Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana / Life Care Clinic
state: Indiana
city: Boston
country: United States
facility: Harvard (Massachusetts Gen Hosp)
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - West Campus
state: Massachusetts
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Chelsea Ctr
state: New York
city: New York
country: United States
facility: Cornell Univ Med Ctr
state: New York
city: Rochester
country: United States
facility: Univ of Rochester Medical Center
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Columbus
country: United States
facility: Ohio State Univ Hosp Clinic
state: Ohio
city: Philadelphia
country: United States
facility: Univ of Pennsylvania at Philadelphia
state: Pennsylvania
Study officials:
name: David Wohl
role: STUDY_CHAIR
name: Joe Eron
role: STUDY_CHAIR
name: Roy Gulick
role: STUDY_CHAIR
References: