1 suppressive valacyclovir therapy soon after initial genital herpes: clinical efficacy and impact...
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Suppressive Valacyclovir Therapy Soon Suppressive Valacyclovir Therapy Soon After Initial Genital Herpes: Clinical After Initial Genital Herpes: Clinical
Efficacy and Impact on Herpes-Related Efficacy and Impact on Herpes-Related Quality of LifeQuality of Life
Suppressive Valacyclovir Therapy Soon Suppressive Valacyclovir Therapy Soon After Initial Genital Herpes: Clinical After Initial Genital Herpes: Clinical
Efficacy and Impact on Herpes-Related Efficacy and Impact on Herpes-Related Quality of LifeQuality of Life
Hunter HandsfieldTerri Warren
Victory MurphyMica 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 HerpesRationale
Early Suppressive Therapy for Genital HerpesRationale
• 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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• 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
Early Suppressive Therapy for Genital HerpesPurpose
Early Suppressive Therapy for Genital HerpesPurpose
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Study DesignStudy Design
• 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 DesignStudy Design
• Laboratory tests
- HSV culture and/or PCR of lesions
- Glycoprotein G-based serology for HSV-1 and HSV-2 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 DesignStudy Design
• 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
Herpes Related Psychological Impact Assessment (HRPIA)
Previously known as Herpes Related Quality of Life
• 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
Herpes Related Psychological Impact Assessment: Sample Items
• 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 muchQuite a bitA little Not at all
0123
Higher scoreis better andrise in scoreindicatesimprovement
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• Intent to treat (ITT), regardless of diagnostic confirmation
-HSV-2
-HSV-1
-HSV, type unknown
-HSV not documented
• Separate analysis of cases with documented HSV-2 infection
Data AnalysisData Analysis
N
75
22
2
20
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Study PopulationStudy Population
• Age, yr, mean + SD• Female, No. (%)• White, No. (%)• New partner 2 mo, No. (%)• HSV diagnosis, No. (%)
- HSV-2- HSV-1- HSV, type unknown- HSV unconfirmed
• HRPIA score, mean + SD• Followed >3 mo, No. (%)
28.5 + 8.9 35 (58) 49 (82) 29 (48)
38 (63) 9 (15) 1 (2) 12 (20) 28.6 + 14.6 44 (73)
29.0 + 8.8 43 (73) 47 (80) 20 (34)
37 (63) 13 (22) 1 (2) 8 (14)31.2 + 14.8 44 (75)
ValacyclovirN=60
PlaceboN=59
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Recurrent Herpes Outbreaks During Follow-up: ITT Analysis
Recurrent Herpes Outbreaks During Follow-up: ITT Analysis
• Outbreak-free, No. (%)
• Number of outbreaks
Mean + SD
Median
Range
35 (58)
0.7 + 1.0
0
0 - 5
19 (32)
1.6 + 2.0 1 0 - 11
0.006
0.004
ValacyclovirN=60
PlaceboN=59 P
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Recurrent Herpes Outbreaks During Follow-up: ITT Analysis
Recurrent Herpes Outbreaks During Follow-up: ITT Analysis
No. of Outbreaks
35
19
15
21
7 63
13
0
10
20
30
40
50
60
0 1 2 >3
ValacyclovirPlacebo
Per
cen
t o
f P
atie
nts
Bars display no.of subjects
P = 0.004
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Recurrent Herpes Outbreaks During Follow-up: Confirmed HSV-2
Recurrent Herpes Outbreaks During Follow-up: Confirmed HSV-2
• Outbreak-free, No. (%)
• Number of outbreaks
Mean + SD
Median
Range
18 (47)
0.9 + 1.2 1 0 - 5
10 (27)
2.0 + 2.4 1 1 - 11
0.095
0.011
ValacyclovirN=38
PlaceboN=37 P
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Recurrent Herpes Outbreaks During Follow-up: Confirmed HSV-2
Recurrent Herpes Outbreaks During Follow-up: Confirmed HSV-2
No. of Outbreaks
18
10 9 10
65
3
12
0
10
20
30
40
50
60
0 1 2 >3
ValacyclovirPlacebo
Per
cen
t o
f P
atie
nts
Bars display no.of subjects
P = 0.012
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Herpes-Related Psychological Impact Assessment: ITT Analysis
Herpes-Related Psychological Impact Assessment: ITT Analysis
• 0 3 mo
• 0 6 mo
4240
14.1 + 12.515.5 + 15.0
N
Valacyclovir
10.1 + 8.9 9.7 + 11.1
0.100.052
PlaceboP
Change in HRPIA Score, Mean + SD
4541
N
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Herpes-Related Psychological Impact Assessment: Confirmed HSV-2
Herpes-Related Psychological Impact Assessment: Confirmed HSV-2
• 0 3 mo
• 0 6 mo
2725
14.0 + 13.414.6 + 16.4
N
Valacyclovir
8.0 + 6.9 6.1 + 9.1
0.0390.023
Placebo
P
Change in HRPIA Score, Mean + SD
3028
N
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Early Suppressive Therapy for Genital HerpesSummary
Early Suppressive Therapy for Genital HerpesSummary
• 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 HerpesLimitations
Early Suppressive Therapy for Genital HerpesLimitations
• 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
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Early Suppressive Therapy for Genital HerpesConclusions
Early Suppressive Therapy for Genital HerpesConclusions
• 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 HerpesAcknowledgments
Early Suppressive Therapy for Genital HerpesAcknowledgments
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