Valganciclovir to Reduce T Cell Activation in HIV Infection

Study Overview
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Brief Summary
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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.

Official Title
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Valganciclovir to Reduce T Cell Activation in HIV Infection

Conditions
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HIV Infections, Cytomegalovirus Infections

Intervention / Treatment
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* Drug: Valganciclovir
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valganciclovir<br>900mg PO qd | Drug: Valganciclovir<br>* 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.<br>* Other names: Placebo;|
| Placebo Comparator: Placebo<br>900mg PO qd | Drug: Placebo<br>* Placebo designed to resemble Valganciclovir<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, CMV, T Cell activation, Valganciclovir