Valganciclovir to Reduce T Cell Activation in HIV Infection

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Cytomegalovirus Infections
• Intervention / Treatment: Drug: Valganciclovir; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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: Placebo; Valganciclovir (Valcyte)
Placebo Comparator: Placebo; 900mg PO qd	Drug: Placebo; Placebo designed to resemble Valganciclovir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CMV DNA Shedding From Baseline to 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.	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	Change from baseline at week 12	Baseline and Week 12
Number of Participants With Positive CMV DNA After a 4-week Washout Period	Number of Participants with positive CMV DNA at any site at week 12	Week 12
Change in CD4 Counts After a 4-week Washout Period	Change from baseline at week 12	Week 12

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: Roche Pharma AG
• Investigators: Principal Investigator: Peter W. Hunt, M.D., University of California, San Francisco

Publications and helpful links

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

Study record dates

Study Major Dates

• Study Start: August 1, 2006
• Primary Completion (Actual): October 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: December 9, 2005
• First Submitted That Met QC Criteria: December 9, 2005
• First Posted (Estimate): December 12, 2005

Study Record Updates

• Last Update Posted (Actual): July 31, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: HIV; CMV; Valganciclovir; T Cell activation
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: H10775-26933-01; SFGH GCRC #976; 5 P30 AI 27763 - Hunt; Roche VAL 104