Transcript Suppressive Valacyclovir Therapy Soon After Initial Genital Herpes: Clinical Efficacy and Impact on Herpes-Related Quality of Life Hunter Handsfield Terri Warren Victory Murphy Mica Werner University of Washington.

Suppressive Valacyclovir Therapy Soon
After Initial Genital Herpes: Clinical
Efficacy and Impact on Herpes-Related
Quality of Life
Hunter Handsfield
Terri Warren
Victory Murphy
Mica Werner
University of Washington and Public Health - Seattle &
King County, Seattle, WA
Westover Heights Clinic, Portland, OR
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Early Suppressive Therapy for Genital Herpes
Rationale
• Genital herpes is the most prevalent STD in the US
• It is the one of greatest concern to sexually active
people in the US behind HIV/AIDS
• The need for suppressive therapy may be greatest in
the first 6-12 months after acquisition when:
Outbreaks most common
Most viral shedding
Most psychological distress
• But suppression has been studied in persons with
genital herpes a year or more in duration
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Early Suppressive Therapy for Genital Herpes
Purpose
• To determine the efficacy of suppressive
treatment with valacyclovir initiated very early
in the course of infection
• Endpoints:
- No. of symptomatic recurrences
- Number of patients recurrence free during follow-up
- Psychological effect of genital herpes
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Study Design
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•
•
•
Double-blind, placebo-controlled, randomized trial
Heterosexual men and women
HIV negative by history
Clinical diagnosis of first episode genital herpes
• within 60 days prior to enrollment or
• within 120 days of first diagnosis and within 60
days of first recurrence
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Study Design
•
•
•
•
Laboratory tests
- HSV culture and/or PCR of lesions
- Glycoprotein G-based serology for HSV-1 and HSV2 at enrollment; follow-up serology if initial PCR or
culture negative
First episode treatment given for 10 days, if indicated
Then valacyclovir 1 g or placebo QD for 6 months
Recurrences treated with open-label valacyclovir 500
mg bid for 5 days; study drug withheld during this
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Study Design
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Follow-up
- Clinic visits at enrollment, 1 mo, 3 mo, 6 mo and
for first suspected recurrent outbreak
- Telephone follow-up 2 wk, 2 mo, 4 mo, 5 mo
•
First recurrence assessed in person, subsequent
outbreaks reported by telephone
•
Herpes-related psychological impact evaluated at
baseline, 3 mo and 6 mo
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Herpes Related Psychological Impact Assessment
(HRPIA)
Previously known as Herpes Related Quality of Life
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•
•
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Self-administered, 5-6 min
20 items, Likert scale (0-3 points)
Minimum score 0, maximum 60
Subject areas
- Self-esteem
- Social functioning
- Sexual functioning
- Personal relationships
- Mental health
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Herpes Related Psychological Impact
Assessment: Sample Items
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•
•
•
Herpes affects my self confidence
Herpes is affecting my sex life
I get depressed about having herpes
Herpes makes makes it difficult to plan ahead
Very much
Quite a bit
A little
Not at all
0
1
2
3
Higher score
is better and
rise in score
indicates
improvement
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Data Analysis
• Intent to treat (ITT), regardless of diagnostic
N
confirmation
75
- HSV-2
22
- HSV-1
2
- HSV, type unknown
- HSV not documented 20
• Separate analysis of cases with documented
HSV-2 infection
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Study Population
Valacyclovir
N=60
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•
•
•
•
Age, yr, mean + SD
28.5 + 8.9
Female, No. (%)
35 (58)
White, No. (%)
49 (82)
New partner 2 mo, No. (%) 29 (48)
HSV diagnosis, No. (%)
- HSV-2
38 (63)
- HSV-1
9 (15)
- HSV, type unknown
1 (2)
- HSV unconfirmed
12 (20)
• HRPIA score, mean + SD
28.6 + 14.6
• Followed >3 mo, No. (%)
44 (73)
Placebo
N=59
29.0 + 8.8
43 (73)
47 (80)
20 (34)
37 (63)
13 (22)
1 (2)
8 (14)
31.2 + 14.8
44 (75)
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Recurrent Herpes Outbreaks During Followup: ITT Analysis
Valacyclovir
N=60
• Outbreak-free,
No. (%)
• Number of
outbreaks
Mean + SD
Median
Range
Placebo
N=59
P
35 (58)
19 (32)
0.006
0.7 + 1.0
0
0-5
1.6 + 2.0
1
0 - 11
0.004
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Percent of Patients
Recurrent Herpes Outbreaks During Followup: ITT Analysis
60
50
Valacyclovir
Placebo
35
40
P = 0.004
30
21
19
15
20
13
10
7
6
0
Bars display no.
of subjects
0
1
2
No. of Outbreaks
3
>3
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Recurrent Herpes Outbreaks During Follow-up:
Confirmed HSV-2
Valacyclovir
N=38
• Outbreak18 (47)
free, No. (%)
• Number of
outbreaks
Mean + SD 0.9 + 1.2
1
Median
0-5
Range
Placebo
N=37
P
10 (27)
0.095
2.0 + 2.4
1
1 - 11
0.011
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Recurrent Herpes Outbreaks During Followup: Confirmed HSV-2
Percent of Patients
60
Valacyclovir
Placebo
50
18
40
P = 0.012
30
12
10
20
10
9
6
10
5
3
0
Bars display no.
of subjects
0
1
2
No. of Outbreaks
>3
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Herpes-Related Psychological Impact
Assessment: ITT Analysis
Change in HRPIA Score, Mean + SD
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•
0
0
3 mo
6 mo
Valacyclovir
N
42 14.1 + 12.5
40 15.5 + 15.0
Placebo
N
45 10.1 + 8.9
41 9.7 + 11.1
P
0.10
0.052
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Herpes-Related Psychological Impact
Assessment: Confirmed HSV-2
Change in HRPIA Score, Mean + SD
•
•
0
0
3 mo
6 mo
Valacyclovir
N
27 14.0 + 13.4
25 14.6 + 16.4
Placebo
N
30
28
8.0 + 6.9
6.1 + 9.1
P
0.039
0.023
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Early Suppressive Therapy for Genital Herpes
Summary
• Suppressive therapy with valacyclovir given
within 60-120 days after acquisition of genital
herpes is superior to placebo in:
Reducing the # of symptomatic recurrent
outbreaks
Ameliorating psychological impact
• Suppression may be less effective in
preventing symptomatic recurrences in early
herpes than in infections >1 year duration
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Early Suppressive Therapy for Genital Herpes
Limitations
• Small trial with limited statistical power
• All except the first recurrent outbreaks were
self-diagnosed by the patients which may be
hypervigilance in newly diagnosed patients rather
than actual outbreaks
• Recurrence rates have not yet been adjusted for
duration of follow-up (I.e. some followed shorter
time periods, some longer
• No data on subclinical shedding or transmission 20
Early Suppressive Therapy for Genital Herpes
Conclusions
• Early valacyclovir suppressive therapy is
effective in reducing recurrences and improving
psychological adjustment
• Further study is needed to confirm and extend
these pilot results (Planning underway for a
multicenter RCT)
• The present results support such therapy for
selected patients. Counsel patients that their
partners may not be protected from transmission
even while on suppression.
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Early Suppressive Therapy for Genital Herpes
Acknowledgments
Bob Deeter, formerly of GlaxoSmithKline
Jennifer Almekinder, GlaxoSmithKline
Jim Phillips, Sage Statistical Solutions
Westover Heights Clinic staff
Public Health - Seattle & King County STD Clinic
staff
The patients who served and the providers who
referred them
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