Valganciclovir to Reduce T Cell Activation in HIV Infection - Full Text View

Purpose

The purpose of this study is to determine whether treatment with valganciclovir decreases T cell activation levels among HIV-infected patients with asymptomatic cytomegalovirus (CMV) co-infection, potentially improving immune responses to antiretroviral therapy.

Condition	Intervention	Phase
HIV Infections Cytomegalovirus Infections	Drug: Valganciclovir Drug: Placebo	Phase 4


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Valganciclovir to Reduce T Cell Activation in HIV Infection

Resource links provided by NLM:

MedlinePlus related topics: Cytomegalovirus Infections HIV/AIDS

Drug Information available for: Valganciclovir hydrochloride

Genetic and Rare Diseases Information Center resources: Cytomegalic Inclusion Disease

U.S. FDA Resources

Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:

Change in %CD38+ Human Leukocyte Antigen-D-related (HLA-DR)+ CD8+ T Cells From Baseline to Week 8. [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]
The percentage of activated (CD38+ HLA-DR+) CD8+ T cells was measured on fresh whole blood at screening/baseline. T cell activation was measured on peripheral blood mononuclear cells (PBMCs)in batch at the end of the study.

Secondary Outcome Measures:

Change in CMV DNA Shedding From Baseline to Week 8. [ Time Frame: week 8 ] [ Designated as safety issue: No ]
Change in percentage of participants with detectable CMV DNA. Herpesvirus DNA levels were assessed by polymerase chain reaction (lower limit of detection, 150 copies/mL) on saliva and seminal plasma.
Change in Cluster of Differentiation 4 (CD4) Counts and Plasma HIV RNA Levels at Week 8. [ Time Frame: week 8 ] [ Designated as safety issue: No ]
%CD38+HLA-DR+ CD8+ T Cells After a 4-week Washout Period [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change in CMV DNA Shedding After a 4-week Washout Period [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
Change in CD4 Counts and Plasma HIV RNA Levels After a 4-week Washout Period [ Time Frame: Week 12 ] [ Designated as safety issue: No ]


Enrollment:	30
Study Start Date:	August 2006
Study Completion Date:	November 2008
Primary Completion Date:	October 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Valganciclovir 900mg PO qd	Drug: Valganciclovir 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone. Other Names: Valganciclovir (Valcyte) Placebo
Placebo Comparator: Placebo 900mg PO qd	Drug: Placebo Placebo designed to resemble Valganciclovir

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Infection with HIV >1 year in duration.
Age >18
Cytomegalovirus (CMV) antibody positive.
All Cluster of Differentiation 4 (CD4)+ T cell counts in the last year and at screening <350 cells/mm3
On a stable highly addictive antiretroviral therapy (HAART) regimen (DHHS definition) for the preceding 6 months.
- 90% adherence to antiretroviral therapy within the preceding 30 days.
Females of childbearing potential must have a negative serum pregnancy test at screening and all subjects must agree to use a double-barrier method of contraception throughout the study period.
Screening %Cluster of differentiation 38 (CD38)+ Human leukocyte antigen-D-related (HLA-DR)+ Cluster of differentiation 8 (CD8)+ T cells >10%

Exclusion Criteria:

Patients intending to modify antiretroviral therapy in the next 16 weeks.
Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
Evidence of active symptomatic CMV end-organ disease.
Treatment with valganciclovir or ganciclovir in the past 30 days.
Concurrent treatment with immunomodulatory drugs.
Concurrent treatment with nephrotoxic drugs
Screening absolute neutrophil count <1,000 cells/mm3, platelet count <100,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <50 mL/minute.
Men who are considering having children will also be excluded given potential effects of valganciclovir on spermatogenesis.
Pregnant or breastfeeding women

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00264290

Locations


United States, California
San Francisco General Hospital - General Clinical Research Center
San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

Roche Pharma AG

Investigators


Principal Investigator:	Peter W. Hunt, M.D.	University of California, San Francisco

More Information

Publications:

Hunt PW, Martin JN, Sinclair E, Bredt B, Hagos E, Lampiris H, Deeks SG. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003 May 15;187(10):1534-43. Epub 2003 Apr 23.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Hunt PW, Martin JN, Sinclair E, Epling L, Teague J, Jacobson MA, Tracy RP, Corey L, Deeks SG. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis. 2011 May 15;203(10):1474-83. doi: 10.1093/infdis/jir060.


Responsible Party:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00264290 History of Changes
Other Study ID Numbers:	H10775-26933-01, SFGH GCRC #976, 5 P30 AI 27763 - Hunt, Roche VAL 104
Study First Received:	December 9, 2005
Results First Received:	August 13, 2013
Last Updated:	November 7, 2013
Health Authority:	United States: Institutional Review Board

Keywords provided by University of California, San Francisco:


HIV CMV T Cell activation Valganciclovir

Additional relevant MeSH terms:


Acquired Immunodeficiency Syndrome Communicable Diseases Cytomegalovirus Infections HIV Infections Infection DNA Virus Infections Herpesviridae Infections Immune System Diseases Immunologic Deficiency Syndromes Lentivirus Infections RNA Virus Infections	Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Virus Diseases Ganciclovir Valganciclovir Anti-Infective Agents Antiviral Agents Pharmacologic Actions Therapeutic Uses

ClinicalTrials.gov processed this record on March 01, 2015