Clinical trial NCT00264290: Valganciclovir to Reduce T Cell Activation in HIV Infection
Official title: Valganciclovir to Reduce T Cell Activation in HIV Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Cytomegalovirus Infections
Keywords: HIV
CMV
T Cell activation
Valganciclovir
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Roche Pharma AG
First posted: 2005-12-12
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in %CD38+ Human Leukocyte Antigen-D-related (HLA-DR)+ CD8+ T Cells From Baseline to Week 8.
timeFrame: Baseline, 8 weeks
Secondary outcomes:
measure: Change in CMV DNA Shedding From Baseline to Week 8.
timeFrame: baseline and week 8
measure: Change in Cluster of Differentiation 4 (CD4) Counts at Week 8
timeFrame: Baseline and week 8
measure: Change in Percent of CD38+HLA-DR+ CD8+ T Cells After a 4-week Washout Period
timeFrame: Baseline and Week 12
measure: Number of Participants With Positive CMV DNA After a 4-week Washout Period
timeFrame: Week 12
measure: Change in CD4 Counts After a 4-week Washout Period
timeFrame: Week 12
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital - General Clinical Research Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Peter W. Hunt, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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;203(10):1474-83. doi: 10.1093/infdis/jir060.