Valganciclovir to Reduce T Cell Activation in HIV Infection

• Sponsor: University of California, San Francisco (Other)
• Overall Status: Completed
• CT.gov ID: NCT00264290
• Collaborator: Roche Pharma AG (Industry)
• Enrollment: 30
• Location: 1
• Arms: 2
• Duration (Months): 27
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Cytomegalovirus Infections	Drug: Valganciclovir; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Valganciclovir to Reduce T Cell Activation in HIV Infection
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Oct 1, 2008
• Actual Study Completion Date: Nov 1, 2008

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Change in Cluster of Differentiation 4 (CD4) Counts at Week 8 [Baseline and week 8]

3. 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

4. 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

5. Change in CD4 Counts After a 4-week Washout Period [Week 12]

   Change from baseline at week 12

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	San Francisco General Hospital - General Clinical Research Center	San Francisco	California	United States	94110

Sponsors and Collaborators

• University of California, San Francisco
• Roche Pharma AG

Investigators

• Principal Investigator: Peter W. Hunt, M.D., University of California, San Francisco

Study Documents (Full-Text)

None provided.

More Information

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. Epub 2003 Apr 23.

• Responsible Party: University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT00264290
• Other Study ID Numbers: H10775-26933-01; SFGH GCRC #976; 5 P30 AI 27763 - Hunt; Roche VAL 104
• First Posted: Dec 12, 2005
• Last Update Posted: Jul 31, 2020
• Last Verified: Jul 1, 2020

• Keywords provided by University of California, San Francisco: HIV; CMV; T Cell activation; Valganciclovir
• Additional relevant MeSH terms: Infections; Communicable Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Cytomegalovirus Infections; Valganciclovir

Study Results

Participant Flow

Recruitment Details	Cytomegalovirus (CMV)-seropositive adults with chronic HIV infection were recruited at one US clinical site.
Pre-assignment Detail	Of 60 screened subjects, 3 refused participation and 27 did not meet eligibility criteria. The most common reason for exclusion was <10% activated Cluster of differentiation * (CD8)+ T cells.

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
Period Title: Intervention (8 Weeks)
STARTED	16	14
COMPLETED	15	14
NOT COMPLETED	1	0
Period Title: Intervention (8 Weeks)
STARTED	15	14
COMPLETED	15	14
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Placebo	Valganciclovir	Total
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.	Total of all reporting groups
Overall Participants	16	14	30
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	14 100%	30 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	50	48	49
Sex: Female, Male (Count of Participants)
Female	0 0%	2 14.3%	2 6.7%
Male	16 100%	12 85.7%	28 93.3%
Region of Enrollment (participants) [Number]
United States	16 100%	14 100%	30 100%

Outcome Measures

1. Primary Outcome

Title	Change in %CD38+ Human Leukocyte Antigen-D-related (HLA-DR)+ CD8+ T Cells From Baseline to Week 8.
Description	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.
Time Frame	Baseline, 8 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	placebo PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.
Measure Participants	15	14
Mean (95% Confidence Interval) [percentage of activated T cells]	1.3	-4.0

2. Secondary Outcome

Title	Change in CMV DNA Shedding From Baseline to Week 8.
Description	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.
Time Frame	baseline and week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valganciclovir	Placebo
Arm/Group Description	900mg PO qd Valganciclovir: 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Placebo: Placebo designed to resemble Valganciclovir
Measure Participants	14	16
Number [percentage of participants]	-36 -225%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Valganciclovir
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	Change in Cluster of Differentiation 4 (CD4) Counts at Week 8
Time Frame	Baseline and week 8

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
Measure Participants	16	14
Mean (95% Confidence Interval) [CD4 cells/mm3]	-1	-8

4. Secondary Outcome

Title	Change in Percent of CD38+HLA-DR+ CD8+ T Cells After a 4-week Washout Period
Description	Change from baseline at week 12
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
Measure Participants	16	14
Mean (95% Confidence Interval) [%CD38+HLA-DR+ CD8+ T cells]	1	-4.1

5. Secondary Outcome

Title	Number of Participants With Positive CMV DNA After a 4-week Washout Period
Description	Number of Participants with positive CMV DNA at any site at week 12
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
Measure Participants	16	14
Count of Participants [Participants]	0 0%	3 21.4%

6. Secondary Outcome

Title	Change in CD4 Counts After a 4-week Washout Period
Description	Change from baseline at week 12
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.	900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background antiretroviral (ARV) regimen alone.
Measure Participants	16	14
Mean (95% Confidence Interval) [cells/mm3]	6	-17

Adverse Events

Time Frame	8 weeks of study treatment and a 4-week Observation Period
Arm/Group Title	Placebo		Valganciclovir
Arm/Group Description	Placebo PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.		900mg PO qd Valganciclovir : 900mg PO qd x 8 weeks followed by 4 weeks of observation on background ARV regimen alone.
All Cause Mortality
	Placebo		Valganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Valganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/16 (6.3%)		0/14 (0%)
Cardiac disorders
congestive heart failure	1/16 (6.3%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Valganciclovir
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/14 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.