Effect of Valacyclovir in the Reduction of HSV-2 Recurrence and Shedding

• Sponsor: University of Alabama at Birmingham (Other)
• Overall Status: Completed
• CT.gov ID: NCT00803543
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 103
• Location: 1
• Arms: 2
• Duration (Months): 62.9
• Patients Per Site Per Month: 1.6

Study Details

Study Description

Brief Summary

The purpose of the study is to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.

Condition or Disease	Intervention/Treatment	Phase
HIV; HIV Infections	Drug: Valacyclovir; Drug: Placebo	N/A

Detailed Description

Most people with herpes infections do not know they have the infection. HSV infections most often occur in areas in and around the mouth and genital tract. HSV Type 1 (HSV-1) usually causes "cold sores" or fever blisters and HSV Type 2 (HSV-2) usually causes lesions in the genital or rectal areas. However, HSV-1 can sometimes cause genital herpes and HSV-2 can cause oral lesions (acquired from oral-genital sex). Herpes Simplex is transmitted by contact with someone who is shedding virus in either the mouth or genital tract, usually by kissing or sexual intercourse. While contact with an active sore can cause transmission, so can contact with saliva or genital secretions that are infected, even when the person does not have an obvious sore. This is called asymptomatic shedding of HSV. Once acquired, the virus has the ability to remain inactive in the nervous system in the area of the mouth or genital region.

Persons with both HIV and HSV-2 often have shedding of both viruses. We know that persons with HSV-2 tend to have increased amounts of HIV in their blood as well. Recently, research studies have found that taking medicine daily to prevent asymptomatic HSV-2 shedding can reduce the amount of HIV found in the blood and in genital secretions. This study seeks to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir (FDA approved drug) reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.

Study Design

• Study Type: Interventional
• Actual Enrollment: 103 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Seroprevalence of HSV-2 in HIV Infected Subjects and the Effect of Daiy Valacyclovir in the Reduction of HSV-2 Recurrences and Viral Shedding
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Valacyclovir This is the arm taking Valacyclovir	Drug: Valacyclovir; 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks; Other Names: There are no other names
Placebo Comparator: Placebo This is the arm taking the placebo	Drug: Placebo; Dosage: Two tablets once a day for 24 weeks; Other Names: There are no other names

Outcome Measures

Primary Outcome Measures

1. Herpes Simplex Virus Type 2 Recurrence [24 Weeks]

   Number of recurrences of genital herpes

2. CD4 Count [24 weeks]

   CD4 count as measured after 24 weeks of placebo versus valacyclovir. Reports as cells/ml

3. Number of Participants With an HIV Viral Load of <500 Copies/ml [24 weeks]

   Number of participants with an HIV Viral Load of <500 copies/ml at 24 weeks

4. Rate of Asymptomatic HSV-2 Genital Shedding [24 weeks]

   Proportion of days on which HSV shedding was observed. This part of the study was performed in a subset of participants (N = 34). Participant collected daily genital specimens for 8 weeks starting at week 16 and continuing through week 24 of the study.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• 19 years or older

• HSV-2 (Herpes simplex virus type 2) seropositive as determined by HerpeSelect-2 ELISA

• Documented HIV-1 seropositive

• Currently receiving HAART for 3 months or longer

• CD4 (cluster of differentiation 4) count 350 or greater

• Women of child bearing potential must agree to use acceptable contraceptive measures during the entire conduct of the study. Acceptable contraceptive methods include one or more of the following: oral hormonal contraceptives, injectable hormonal contraceptives, transdermal hormonal contraceptives, IUD (intrauterine device), diaphragm or cervical cap.

• Willing and able to provide written informed consent, undergo clinical evaluations, and take study drug as directed

Exclusion Criteria:

• History of symptomatic genital herpes, lesions or symptoms consistent with genital herpes, or recurrent undiagnosed symptoms consistent with genital herpes.

• Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir.

• Planned open label use of acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, cidofovir, or foscarnet for oral herpes or other herpes viral infections.

• Medical history of seizures

• Renal insufficiency, defined as serum creatinine greater than 1.5 mg/dl

• AST (aspartate aminotransferase) or ALT (alanine aminotransferase) over 5 times uper limit of normal

• History of thrombotic microangiopathy

• For women, pregnancy as confirmed by a urine or serum pregnancy test.

• Any other condition which, in the opinion of the principal investigator, may compromise the subject's ability to follow study procedures and complete the study.

• Participants with active bacterial STDs (sexually transmitted diseases) may be treated and be eligible for enrollment 14 days after STD therapy is discontinued and symptoms have resolved.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Community Care Building	Birmingham	Alabama	United States	35294

Sponsors and Collaborators

• University of Alabama at Birmingham
• GlaxoSmithKline

Investigators

• Principal Investigator: Nicholas Van Wagoner, MD, University of Alabama at Birmingham

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Nicholas Van Wagoner, MD, Assistant Professor, University of Alabama at Birmingham
• ClinicalTrials.gov Identifier: NCT00803543
• Other Study ID Numbers: F080718009
• First Posted: Dec 5, 2008
• Last Update Posted: Jul 13, 2017
• Last Verified: Jun 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Nicholas Van Wagoner, MD, Assistant Professor, University of Alabama at Birmingham: HSV-2; Herpes Simplex; HSV Type 2; HIV; HIV/HSV; treatment experienced
• Additional relevant MeSH terms: Recurrence; Valacyclovir

Study Results

Participant Flow

Arm/Group Title	Valacyclovir	Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks
Period Title: Overall Study
STARTED	69	34
COMPLETED	45	22
NOT COMPLETED	24	12

Baseline Characteristics

Arm/Group Title	Valacyclovir	Placebo	Total
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks	Total of all reporting groups
Overall Participants	45	22	67
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	45	43	45
Sex: Female, Male (Count of Participants)
Female	8 17.8%	1 4.5%	9 13.4%
Male	37 82.2%	21 95.5%	58 86.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	45 100%	22 100%	67 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	25 55.6%	9 40.9%	34 50.7%
White	20 44.4%	13 59.1%	33 49.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	45 100%	22 100%	67 100%
Absolute CD4 (cluster of differentiation 4) Count (cell/ml) [Mean (Full Range) ]
Mean (Full Range) [cell/ml]	528	693	582
Number with Undetectable Viral Load (participants) [Number]
Number [participants]	40 88.9%	19 86.4%	59 88.1%

Outcome Measures

1. Primary Outcome

Title	Herpes Simplex Virus Type 2 Recurrence
Description	Number of recurrences of genital herpes
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

No participants reported genital herpes recurrence during the study.

Arm/Group Title	Valacyclovir	Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks
Measure Participants	45	22
Number [Recurrence]	0	0

2. Primary Outcome

Title	CD4 Count
Description	CD4 count as measured after 24 weeks of placebo versus valacyclovir. Reports as cells/ml
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valacyclovir	Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks
Measure Participants	45	22
Mean (Full Range) [cells/ml]	536	627.5

3. Primary Outcome

Title	Number of Participants With an HIV Viral Load of <500 Copies/ml
Description	Number of participants with an HIV Viral Load of <500 copies/ml at 24 weeks
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valacyclovir	Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks
Measure Participants	45	22
Number [Participants]	38 84.4%	20 90.9%

4. Primary Outcome

Title	Rate of Asymptomatic HSV-2 Genital Shedding
Description	Proportion of days on which HSV shedding was observed. This part of the study was performed in a subset of participants (N = 34). Participant collected daily genital specimens for 8 weeks starting at week 16 and continuing through week 24 of the study.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Valacyclovir	Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks	Placebo: Dosage: Two tablets once a day for 24 weeks
Measure Participants	26	8
Measure Total Number of Days Assessed	1456	448
Number [Proportion of days]	0.0009	0.0001

Adverse Events

Time Frame	Entire study
Arm/Group Title	Valacyclovir		Placebo
Arm/Group Description	Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks		Placebo: Dosage: Two tablets once a day for 24 weeks
All Cause Mortality
	Valacyclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/22 (0%)
Serious Adverse Events
	Valacyclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/22 (0%)
Other (Not Including Serious) Adverse Events
	Valacyclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/45 (0%)		0/22 (0%)

Limitations/Caveats

Small populations size. High level of patient withdrawal and loss to follow up.

More Information

Certain Agreements

Principal Investigators are NOT 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.