Trial Outcomes & Findings for Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV (NCT NCT00527618)
NCT ID: NCT00527618
Last Updated: 2018-06-07
Results Overview
Weekly measurements of plasma HIV-1 RNA on each drug were compared. The primary analysis was of the average difference in plasma HIV-1 RNA on valacyclovir and acyclovir as determined by a linear mixed model. The median of the average per-participant plasma HIV-1 RNA levels on valacyclovir and valacyclovir is also listed.
COMPLETED
PHASE4
28 participants
26 weeks (12 weeks per drug intervention)
2018-06-07
Participant Flow
We recruited HIV-1/HSV-2 coinfected patients in Seattle, WA, between January 2008 and June 2010.
Of 49 persons screened, 15 were found to be ineligible for reasons including lack of HSV-2 infection (n=5), plans to initiate ART (n=3), undetectable plasma HIV-1 RNA (n=3), neutropenia (n=2), elevated hepatic transaminases (n=1), and incarceration (n=1). The remaining 34 participants were randomized.
Participant milestones
| Measure |
Acyclovir Followed by Valacyclovir
Acyclovir 400 mg twice daily, followed by a two-week washout period, then valacyclovir 1000 mg twice daily
|
Valacyclovir Followed by Acyclovir
Valacyclovir 1000 mg twice daily, followed by a two-week washout period, then acyclovir 400 mg twice daily
|
|---|---|---|
|
Week 1-12 (First Intervention)
STARTED
|
16
|
18
|
|
Week 1-12 (First Intervention)
COMPLETED
|
13
|
16
|
|
Week 1-12 (First Intervention)
NOT COMPLETED
|
3
|
2
|
|
Week 13-14 (Washout)
STARTED
|
13
|
16
|
|
Week 13-14 (Washout)
COMPLETED
|
12
|
16
|
|
Week 13-14 (Washout)
NOT COMPLETED
|
1
|
0
|
|
Week 15-18 (Second Intervention)
STARTED
|
12
|
16
|
|
Week 15-18 (Second Intervention)
COMPLETED
|
12
|
13
|
|
Week 15-18 (Second Intervention)
NOT COMPLETED
|
0
|
3
|
Reasons for withdrawal
| Measure |
Acyclovir Followed by Valacyclovir
Acyclovir 400 mg twice daily, followed by a two-week washout period, then valacyclovir 1000 mg twice daily
|
Valacyclovir Followed by Acyclovir
Valacyclovir 1000 mg twice daily, followed by a two-week washout period, then acyclovir 400 mg twice daily
|
|---|---|---|
|
Week 1-12 (First Intervention)
Lost to Follow-up
|
3
|
1
|
|
Week 1-12 (First Intervention)
Adverse Event
|
0
|
1
|
|
Week 13-14 (Washout)
Lost to Follow-up
|
1
|
0
|
|
Week 15-18 (Second Intervention)
Lost to Follow-up
|
0
|
1
|
|
Week 15-18 (Second Intervention)
Censored on initiation of HAART
|
0
|
1
|
|
Week 15-18 (Second Intervention)
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV
Baseline characteristics by cohort
| Measure |
Entire Study Population
n=34 Participants
This includes all 34 participants who were randomized. A subset of 28 participants were included in the analysis since only 28 participants contributed samples on both arms of the crossover study.
|
|---|---|
|
Age, Continuous
|
43 Years
n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
28 Participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Caucasian
|
23 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
African-American
|
9 participants
n=99 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 participants
n=99 Participants
|
|
CD4 Count
|
526 cells/microliter
n=99 Participants
|
|
Plasma HIV-1 RNA
|
3.84 log10 copies/mL
n=99 Participants
|
PRIMARY outcome
Timeframe: 26 weeks (12 weeks per drug intervention)Population: Of the 34 participants who were randomized, 6 participants did not contribute to both arms of the study. The final analysis set therefore included 28 participants. 27 participants had plasma HIV-1 RNA levels available for analysis, since samples for one participant were persistently inhibited.
Weekly measurements of plasma HIV-1 RNA on each drug were compared. The primary analysis was of the average difference in plasma HIV-1 RNA on valacyclovir and acyclovir as determined by a linear mixed model. The median of the average per-participant plasma HIV-1 RNA levels on valacyclovir and valacyclovir is also listed.
Outcome measures
| Measure |
Acyclovir
n=27 Participants
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=27 Participants
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
The Quantity of HIV-1 RNA in Plasma While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.
|
4.08 log10 copies/mL
Interval 1.17 to 5.33
|
3.68 log10 copies/mL
Interval 1.17 to 4.99
|
PRIMARY outcome
Timeframe: The first four weeks of each interventionPopulation: Of the 34 participants who were randomized, 6 participants did not contribute to both arms of the study. The final analysis set therefore included 28 participants.
HSV DNA quantitated from daily self-collected genital swabs for the first four weeks of each drug intervention. The shedding rate was determined by the combined number of swabs with HSV detected divided by the combined number of swabs collected from participants, multiplied by 100.
Outcome measures
| Measure |
Acyclovir
n=28 Participants
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=28 Participants
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
The Genital HSV Shedding Rate While on 400 mg Twice Daily of Acyclovir Versus 1000 mg Twice Daily of Valacyclovir.
|
8.2 percentage of swabs collected with HSV
|
7.8 percentage of swabs collected with HSV
|
SECONDARY outcome
Timeframe: 26 weeks (12 weeks per drug intervention)Population: Of the 34 participants who were randomized, 6 participants did not contribute to both arms of the study. The final analysis set therefore included 28 participants.
The percentage of days with genital herpes lesions was determined by the combined diary days in which genital lesions were recorded divided by the combined number of diary days for participants in the first four weeks of each drug intervention, multiplied by 100.
Outcome measures
| Measure |
Acyclovir
n=28 Participants
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=28 Participants
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
The Effect of Valacyclovir 1 Gram Twice Daily Compared to Acyclovir 400 mg Twice Daily on the Percentage of Days With Genital Herpes Lesions.
|
4.0 percentage of days with genital lesions
|
1.0 percentage of days with genital lesions
|
SECONDARY outcome
Timeframe: The first four weeks of each interventionPopulation: Of the 34 participants who were randomized, 6 participants did not contribute to both arms of the study. The final analysis set therefore included 28 participants.
HSV DNA was quantitated from daily self-collected genital swabs for the four weeks of each drug intervention. The quantity of genital HSV DNA present, when HSV DNA was detected, was compared.
Outcome measures
| Measure |
Acyclovir
n=28 Participants
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=28 Participants
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
The Effect of Valacyclovir 1 g Twice Daily Compared With Acyclovir 400 mg Twice Daily on the Quantity of Genital HSV Detected During Shedding Episodes.
|
3.0 log10 copies/mL
Interval 2.2 to 6.4
|
3.0 log10 copies/mL
Interval 2.2 to 6.8
|
SECONDARY outcome
Timeframe: 72 hoursPopulation: In April 2010, we invited participants, including those who already completed the study, to participate in the substudy. Two participants had plasma HIV-1 RNA \<40 copies/mL at the time of valacyclovir initiation and were excluded from analysis.
Plasma HIV-1 RNA was measured one day prior to, at initiation, and at 6, 24, 48, and 72 hours after initiating valacyclovir. Measurements at 24, 48, and 72 hours were used to determine the rate of HIV-1 RNA decline.
Outcome measures
| Measure |
Acyclovir
n=10 Participants
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
Sub-Study: To Evaluate the Kinetics of Plasma HIV-1 Decline Over the First Three Days of High-dose Valacyclovir Administration.
|
-0.20 log10 copies/mL/day
Interval -0.38 to -0.19
|
—
|
Adverse Events
Acyclovir
Valacyclovir
Serious adverse events
| Measure |
Acyclovir
n=32 participants at risk
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=30 participants at risk
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
3.1%
1/32 • Number of events 1 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
0.00%
0/30 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
Other adverse events
| Measure |
Acyclovir
n=32 participants at risk
Acyclovir, 400 mg orally twice daily (assigned to the acyclovir arm in either the first or second intervention periods)
|
Valacyclovir
n=30 participants at risk
Valacyclovir, 1000 mg orally twice daily (assigned to the valacyclovir arm in either the first or second intervention periods)
|
|---|---|---|
|
Infections and infestations
Upper Resipiratory Tract Infection
|
12.5%
4/32 • Number of events 4 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
10.0%
3/30 • Number of events 3 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/32 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
6.7%
2/30 • Number of events 2 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Nervous system disorders
Headache
|
6.2%
2/32 • Number of events 2 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
3.3%
1/30 • Number of events 1 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Gastrointestinal disorders
Nausea
|
9.4%
3/32 • Number of events 3 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
3.3%
1/30 • Number of events 2 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/32 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
6.7%
2/30 • Number of events 2 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Reproductive system and breast disorders
Yeast vaginitis
|
3.1%
1/32 • Number of events 3 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
6.7%
2/30 • Number of events 3 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
|
Psychiatric disorders
Depression
|
0.00%
0/32 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
6.7%
2/30 • Number of events 2 • 26 weeks
Assessment of any adverse events was performed at each weekly clinic visit during the trial by a study investigator, including 12 weeks during acyclovir administration, 12 weeks during valacyclovir administration and 2 weeks during the washout period.
|
Additional Information
Tara Perti, MD
University of Washington, Virology Research Clinic
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place