Clinical trial NCT00006154: A Study to Evaluate the Use of a Protease Inhibitor and of Interleukin-2 (IL-2) in the Treatment of Early HIV Infection
Official title: Randomized, Controlled, Open Label, Multi-Center Phase III Trial Comparing the Safety and Antiviral Activity of a Protease-Containing Regimen (d4T/ddI/IDV/RTV) Versus a Protease-Sparing Regimen (d4T/ddI/EFV) and the Ability of Interleukin-2 to Purge HIV From Latent Stores in Patients With Acute/Early HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Interleukin-2
Didanosine
Drug Therapy, Combination
Stavudine
HIV Protease Inhibitors
Ritonavir
Indinavir
Virus Latency
Reverse Transcriptase Inhibitors
Anti-HIV Agents
abacavir
efavirenz
Acute Infection
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 165
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to look at the effectiveness of combination anti-HIV drug therapy (with protease inhibitors \[PIs\] or without) in patients with early HIV infections. This study also looks at whether a drug called interleukin-2 (IL-2) can boost the immune system of these patients.

Doctors are not sure which anti-HIV drug combination is best to use in patients who have early HIV infection and have never received anti-HIV treatment. PIs are anti-HIV drugs that decrease viral load (level of HIV in the blood). However, PIs can cause serious side effects in some patients. Doctors would like to know if a drug combination that does not contain a PI is just as good as one that contains PIs.

Detailed description: Studies have suggested that an antiretroviral drug regimen of the non-nucleoside agent efavirenz (EFV) in combination with two nucleoside analogues is effective at achieving maximal viral suppression. This provides an alternative treatment to that of the more toxic PI-containing regimen. This trial examines whether a nonPI regimen with EFV is more beneficial than a PI-containing regimen when each is used in combination with the same two nucleoside analogues. A second part of the study looks at whether the addition of IL-2 may offer immunologic benefits as a co-administered drug.

Patients are randomized to initiate antiretroviral therapy of a PI-based (stavudine/didanosine/ritonavir \[RTV\]/indinavir \[IDV\]) or nonPI-based (stavudine/didanosine/EFV) regimen. Within these treatment arms, they are stratified according to a positive or negative p24 antigen result. At Week 16, patients not achieving maximal viral suppression (lower than 50 copies/ml) have the option to add abacavir (ABC) or other drugs as intensification therapy. Those achieving virologic suppression (less than 50 copies/ml) are randomized either to receive IL-2 or not. At study entry, and after 12 months, tissue samples of CSF, lymph node, and genital secretions are obtained, with permission. Patients have physical exams, women of child-bearing potential have pregnancy tests, and blood samples are drawn at clinic visits 12-16 times a year over 3 years so that virologic and immunologic evaluations may be performed. Compensation for time and transportation is given.

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Have been infected recently with HIV. This will be determined by certain lab tests.
* Are 18 years of age or older.
* Are able to swallow a large number of pills.
* Are willing to use barrier methods of birth control (such as condoms) during the study.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Abuse drugs or alcohol.
* Have any condition that, in the opinion of the investigator, could impair their ability to participate in the study.
* Are breast-feeding or pregnant.
* Have received any prior anti-HIV drugs. (However, use of anti-HIV drugs to try to prevent infection more than 6 months prior to study entry is allowed.)

Primary outcomes:
measure: Virologic: A. Plasma viral load B. Tissue viral load (CNS, lymphoid tissues, genital tract) C. HIV DNA (proviral) levels in circulating mononuclear cells D. Phenotypic and genotypic antiretroviral drug resistance
timeFrame: Throughout study
measure: Immunologic: A. Evaluation of CD4, CD8, CD45RA, CD45RO phenotypes and defined activation markers B. Evaluation of the diversity and persistence of the T cell repertoire (CD4+, CD8+) in the circulation and lymphoid tissues
timeFrame: Throughout study
measure: Immunologic: C. Functional CD4+ cellular assays (class II MHC tetramers) D. Thymic regeneration as studied by the exclusion circle assay E. Evolution of Western blot banding patterns F. Evolution of anti-HIV neutralizing antibody levels
timeFrame: Throughout study
measure: Clinical: A. Minor opportunistic infections or AIDS-defining conditions B. Death C. Clinical or laboratory adverse events D. Evaluation of adherence to therapy E. Evaluation of lipodystrophy
timeFrame: Throughout study
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Viridae Clinical Sciences / University of British Columbia
state: British Columbia
city: Montreal
country: Canada
facility: Centre de traitment d'immunodeficience
state: Quebec
city: Montreal
country: Canada
facility: Centre Hospitalier de la Universite de Montreal (CHUM)
state: Quebec
city: Montreal
country: Canada
facility: Institut Thoracique de Montreal
state: Quebec
Study officials:
name: Rafick-Pierre Sekaly
role: PRINCIPAL_INVESTIGATOR
name: Brian Conway
role: PRINCIPAL_INVESTIGATOR
References: