Hunter Handsfield Terri Warren Victory Murphy Mica Werner

1

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

2

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

3

• 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

4

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

5

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

6

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

7

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

8

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

9

• 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

10

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

11

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

12

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

13

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

14

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

16

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

18

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

19

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

20

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

21

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.

22

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