Clinical trial NCT00000755: A Phase I/II Trial of Vaccine Therapy of HIV-1 Infected Individuals With 50-500 CD4 Cells/mm3
Official title: A Phase I/II Trial of Vaccine Therapy of HIV-1 Infected Individuals With 50-500 CD4 Cells/mm3
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Vaccines, Synthetic
HIV-1
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
HIV Envelope Protein gp120
AIDS Vaccines
HIV Therapeutic Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Genentech, Inc.
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 168
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To examine the response of HIV-1 infected patients to vaccination with gp120/HIV-1MN antigen. To determine the effect of antiretroviral therapy on vaccine responsiveness.

Fifty percent of HIV-1 infected individuals remain symptom free for 8-12 years. It has been hypothesized that HIV-specific immune responses are responsible for the period of relative quiescence of viral replication. Recent studies suggest that these immune functions can be augmented by vaccination with HIV-derived antigens.

Detailed description: Fifty percent of HIV-1 infected individuals remain symptom free for 8-12 years. It has been hypothesized that HIV-specific immune responses are responsible for the period of relative quiescence of viral replication. Recent studies suggest that these immune functions can be augmented by vaccination with HIV-derived antigens.

Patients are randomized to receive rgp120/HIV-1MN vaccine or alum adjuvant placebo by intramuscular injection at weeks 0, 4, 8, 12, 16, and 20, with or without daily oral zidovudine (AZT) or their current stable dose of antiretroviral therapy. After completing the primary vaccination series, patients are permitted to continue into an extension phase, in which they receive a booster vaccination at weeks 28, 36, and 44. Patients will be stratified by CD4 count: 350-500, 200-349, and 50-199 cells/mm3. A fourth group with counts of 350-500 cells/mm3 will serve as a pilot group and receive vaccine only.

Eligibility criteria: Inclusion Criteria

Required immediately prior to study entry:

* A minimum of 2 and a maximum of 12 months of AZT therapy at 500-600 mg/day (does not apply to the pilot group patients receiving vaccine only and to patients with CD4 counts of 50-199 cells/mm3).

Concurrent Medication:

Allowed:

* PCP prophylaxis.
* Rifabutin and clarithromycin (in patients with CD4 counts of 50-199 cells/mm3 only).
* Short-term nonsteroidal anti-inflammatory therapy for acute conditions.
* Short intermittent cycles of acyclovir.

Patients must have:

* HIV infection, with CD4 count of 50-500 cells/mm3.
* No active opportunistic infection (patients with CD4 counts of 50-199 cells/mm3 may have a history of an opportunistic infection).
* Consent of parent, guardian, or person with power of attorney, if less than 18 years of age.
* B-cell lines established in order to be vaccinated.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Known or suspected allergies to any vaccine components.

Concurrent Medication:

Excluded:

* Agents with immunosuppressive activity.
* Antiretroviral therapies other than AZT (except in patients with CD4 counts of 50-199 cells/mm3).
* Interferon.
* Parenteral therapies (including SC allergy medications and chemotherapy for Kaposi's sarcoma).
* Steroids.
* Hematopoietins.

Prior Medication:

Excluded within 12 weeks prior to study entry:

* Agents with immunosuppressive activity.
* Antiretroviral therapies other than AZT (except in patients with CD4 counts of 50-349 cells/mm3).
* Interferon.
* Parenteral therapies (including SC allergy medications and chemotherapy for Kaposi's sarcoma).
* Steroids.
* Hematopoietins.

Active drug abuse.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Schooley RT
role: STUDY_CHAIR
name: Walker B
role: STUDY_CHAIR
References:
citation: Kuritzkes DR, Spino C, Valentine F, Schooley RT. Association of plasma HIV-1 RNA, CD4 count, and immune response in patients with 50-500 CD4 cells/ul. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:204 (abstract no 757)
citation: Schooley RT, Spino C, Chiu S, DeGruttola V, Kuritzkes DR. Poor immunogenicity of HIV-1 envelope vaccines with alum or MF59 aduvant in HIV-infected individuals: results of two randomized trials. Conf Retroviruses Opportunistic Infect. 1997 Jan 22-26;4th:204 (abstract no 756)
citation: Schooley RT, Spino C, Kuritzkes D, Walker BD, Valentine FA, Hirsch MS, Cooney E, Friedland G, Kundu S, Merigan TC Jr, McElrath MJ, Collier A, Plaeger S, Mitsuyasu R, Kahn J, Haslett P, Uherova P, deGruttola V, Chiu S, Zhang B, Jones G, Bell D, Ketter N, Twadell T, Chernoff D, Rosandich M. Two double-blinded, randomized, comparative trials of 4 human immunodeficiency virus type 1 (HIV-1) envelope vaccines in HIV-1-infected individuals across a spectrum of disease severity: AIDS Clinical Trials Groups 209 and 214. J Infect Dis. 2000 Nov;182(5):1357-64. doi: 10.1086/315860. Epub 2000 Oct 9.