Valganciclovir to Reduce T Cell Activation in HIV Infection

Phase 4

Completed

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.

Recruitment & 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

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	900mg PO qd
Valganciclovir	Valganciclovir	900mg PO qd

Primary Outcome Measures

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

Name	Time	Method
Change in CMV DNA Shedding From Baseline to Week 8.	baseline and 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.
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	Change from baseline at week 12
Number of Participants With Positive CMV DNA After a 4-week Washout Period	Week 12	Number of Participants with positive CMV DNA at any site at week 12
Change in CD4 Counts After a 4-week Washout Period	Week 12	Change from baseline at week 12