Valganciclovir to Reduce T Cell Activation in HIV Infection

NCT00264290 | Completed Phase 4 Results

• 5 other identifiers: H10775-26933-01SFGH GCRC #9765 P30 AI 27763 - HuntRoche VAL 1045P30AI027763
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections; Cytomegalovirus Infections

Keywords

HIV; CMV; T Cell activation; Valganciclovir

Outcome Measures

Primary Outcomes (1)

• Change in %CD38+ Human Leukocyte Antigen-D-related (HLA-DR)+ CD8+ T Cells From Baseline to Week 8.

  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.

  Baseline, 8 weeks

Secondary Outcomes (5)

• Change in CMV DNA Shedding From Baseline to Week 8.

  baseline and week 8

• Change in Cluster of Differentiation 4 (CD4) Counts at Week 8

  Baseline and week 8

• Change in Percent of CD38+HLA-DR+ CD8+ T Cells After a 4-week Washout Period

  Baseline and Week 12

• Number of Participants With Positive CMV DNA After a 4-week Washout Period

  Week 12

• Change in CD4 Counts After a 4-week Washout Period

  Week 12

Study Arms (2)

Valganciclovir

EXPERIMENTAL

900mg PO qd

Drug: Valganciclovir

Placebo

PLACEBO COMPARATOR

900mg PO qd

Drug: Placebo

Interventions

Valganciclovir DRUG

900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.

Also known as: Valganciclovir (Valcyte), Placebo

Valganciclovir

Placebo DRUG

Placebo designed to resemble Valganciclovir

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• % 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%

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Roche Pharma AG: collaborator

Study Sites (1)

San Francisco General Hospital - General Clinical Research Center

San Francisco, California, 94110, United States

Location

Related Publications (2)

• 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. doi: 10.1086/374786. Epub 2003 Apr 23.

  PMID: 12721933 BACKGROUND

• 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.

  PMID: 21502083 RESULT

MeSH Terms

Conditions

HIV Infections; Cytomegalovirus Infections

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Herpesviridae Infections; DNA Virus Infections

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Peter W. Hunt, M.D.
• Organization: University of California, San Francisco

phunt@php.ucsf.edu

415-476-4082

Study Officials

• Peter W. Hunt, M.D.

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2005
• First Posted: December 12, 2005
• Study Start: August 1, 2006
• Primary Completion: October 1, 2008
• Study Completion: November 1, 2008
• Last Updated: July 31, 2020
• Results First Posted: November 8, 2013

Record last verified: 2020-07

Locations

US (1)