Valganciclovir to Reduce T Cell Activation in HIV Infection

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections; Cytomegalovirus Infections	Drug: Valganciclovir; Drug: Placebo	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	30 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Valganciclovir to Reduce T Cell Activation in HIV Infection
Study Start Date :	August 2006
Actual Primary Completion Date :	October 2008
Actual Study Completion Date :	November 2008

Arms and Interventions

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Arm	Intervention/treatment
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

Outcome Measures

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Primary Outcome Measures :

1. Change in %CD38+ Human Leukocyte Antigen-D-related (HLA-DR)+ CD8+ T Cells From Baseline to Week 8. [ Time Frame: Baseline, 8 weeks ]
   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 :

1. Change in CMV DNA Shedding From Baseline to Week 8. [ Time Frame: week 8 ]
   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.
2. Change in Cluster of Differentiation 4 (CD4) Counts and Plasma HIV RNA Levels at Week 8. [ Time Frame: week 8 ]
3. %CD38+HLA-DR+ CD8+ T Cells After a 4-week Washout Period [ Time Frame: Week 12 ]
4. Change in CMV DNA Shedding After a 4-week Washout Period [ Time Frame: Week 12 ]
5. Change in CD4 Counts and Plasma HIV RNA Levels After a 4-week Washout Period [ Time Frame: Week 12 ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations 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.

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
First Posted:	December 12, 2005
Results First Posted:	November 8, 2013
Last Update Posted:	December 3, 2013
Last Verified:	November 2013

Keywords provided by University of California, San Francisco:

HIV; CMV; T Cell activation; Valganciclovir

Additional relevant MeSH terms:

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