Valganciclovir to Reduce T Cell Activation in HIV Infection

HIV Infections Clinical Trial

Official title:

Valganciclovir to Reduce T Cell Activation in HIV Infection

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00264290
• Other study ID #: H10775-26933-01
• Secondary ID: SFGH GCRC #9765
• Status: Completed
• Phase: Phase 4
• Start date: August 2006
• Est. completion date: November 2008

Study information

• Verified date: July 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2008
• Est. primary completion date: October 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• Cytomegalovirus Infections
• HIV Infections
• Infection

Intervention

Drug:
• Valganciclovir
900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
• Placebo
Placebo designed to resemble Valganciclovir

Locations

Country	Name	City	State
United States	San Francisco General Hospital - General Clinical Research Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	Roche Pharma AG

Country where clinical trial is conducted

United States, 

References & 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. Epub 2003 Apr 23. — View Citation

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;20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Change in Cluster of Differentiation 4 (CD4) Counts at Week 8		Baseline and week 8
Secondary	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
Secondary	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
Secondary	Change in CD4 Counts After a 4-week Washout Period	Change from baseline at week 12	Week 12