Clinical trial NCT00050063: Effects of Therapeutic HIV Vaccination on Control of HIV After Discontinuation of Anti-HIV Drugs
Official title: A Rollover Study of A5058s: A Phase II Trial to Evaluate the Ability of Vaccine-Induced Helper and CTL Responses to Control Viremia in the Absence of Antiretroviral Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: HIV Therapeutic Vaccine
Treatment Experienced
AIDS Vaccines
Treatment Interruption
Viral Load
T-Lymphocytes, Cytotoxic
T-Lymphocytes, Helper-Inducer
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-11-21
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: The purpose of this study is to determine whether therapeutic HIV vaccines can help the immune system control HIV viral load after anti-HIV drugs are discontinued.

Detailed description: This study is a rollover study for patients who participated in A5058s: Augmentation of HIV-Specific Helper and CTL Responses Through Therapeutic Vaccination in Individuals Receiving Potent Suppressive Antiretroviral Therapies. In A5058s, patients received a series of therapeutic vaccinations to elicit HIV-specific immune responses. This study will examine whether these vaccine-induced responses can control viral load in the absence of antiretroviral therapy (ART).

Upon study entry, patients will discontinue ART. During the first 6 weeks of the study, viral load will be monitored weekly and CD4+ T-cell counts will be monitored every other week. Viral load and CD4+ T-cell counts will be measured every other week from Week 6 through Week 24, then monthly until patients restart ART or until Week 48. Patients who reinitiate ART for any reason will be registered to Step 2 and followed for 10 weeks.

Eligibility criteria: Inclusion Criteria:

* Participation in A5058s and receipt of a minimum of 7 sets of injections on that study
* Continuation of the same stable antiretroviral treatment that was given in A5058s for the last 3 months prior to A5172 entry, unless the regimen was changed for toxicity in the absence of virologic failure
* No less than 6 weeks and no more than 18 weeks since the last injection on A5058s prior to A5172 entry
* CD4+ T-cell count \> 300 cells/mm3 obtained within 30 days prior to study entry
* HIV-1 RNA \< 500 copies/ml obtained within 30 days prior to study entry
* Agreement to use approved methods of contraception

Exclusion Criteria:

* Pregnancy or breast-feeding
* Any of the following within 30 days prior to entry: acute infection requiring antibiotics, outbreak of herpes simplex virus (HSV) or herpes zoster, other acute medical illness, or surgery
* Symptomatic chronic infections other than HIV
* Malignancy that may require systemic therapy
* History of lymph node irradiation
* Use of immunoenhancing or immunosuppressive drugs within 30 days prior to entry, or any underlying disease of sufficient severity that these excluded drugs may be prescribed
* Hydroxyurea within 30 days prior to study entry
* Use of GM-CSF, G-CSF, M-CSF, IFN, IL-2, or other cytokines within 30 days prior to study entry
* Active drug or alcohol use or dependence that would interfere with adherence to study requirements
* Serious illness requiring systemic treatment and/or hospitalization until patient either completes therapy or is clinically stable on therapy for at least 30 days prior to study entry

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Wishard Memorial
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp. of Indiana
state: Indiana
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 Med. Ctr., ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS
state: Massachusetts
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Galveston
country: United States
facility: Univ. of Texas Medical Branch, ACTU
state: Texas
Study officials:
affiliation: Vanderbilt University Medical Center
name: Spyros Kalamus, M. D.
role: STUDY_CHAIR
affiliation: NYU MEDICAL CENTER
name: Fred Valentine, M. D.
role: STUDY_CHAIR
References:
citation: Papasavvas E, Ortiz GM, Gross R, Sun J, Moore EC, Heymann JJ, Moonis M, Sandberg JK, Drohan LA, Gallagher B, Shull J, Nixon DF, Kostman JR, Montaner LJ. Enhancement of human immunodeficiency virus type 1-specific CD4 and CD8 T cell responses in chronically infected persons after temporary treatment interruption. J Infect Dis. 2000 Sep;182(3):766-75. doi: 10.1086/315748. Epub 2000 Aug 17.
citation: Carcelain G, Tubiana R, Samri A, Calvez V, Delaugerre C, Agut H, Katlama C, Autran B. Transient mobilization of human immunodeficiency virus (HIV)-specific CD4 T-helper cells fails to control virus rebounds during intermittent antiretroviral therapy in chronic HIV type 1 infection. J Virol. 2001 Jan;75(1):234-41. doi: 10.1128/JVI.75.1.234-241.2001.
citation: Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001 Feb 15;344(7):472-80. doi: 10.1056/NEJM200102153440702.
citation: Ruiz L, Carcelain G, Martinez-Picado J, Frost S, Marfil S, Paredes R, Romeu J, Ferrer E, Morales-Lopetegi K, Autran B, Clotet B. HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection. AIDS. 2001 Jun 15;15(9):F19-27. doi: 10.1097/00002030-200106150-00001.
citation: Garcia F, Plana M, Vidal C, Cruceta A, O'Brien WA, Pantaleo G, Pumarola T, Gallart T, Miro JM, Gatell JM. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS. 1999 Jul 30;13(11):F79-86. doi: 10.1097/00002030-199907300-00002.