HIV InfectionPhase 3NCT00378976
HSV-2 Suppression to Reduce HIV-1 Levels in HIV-1, HSV-2 Co-infected Men.
A Phase 3 study testing valacyclovir in people with HIV Infection and Herpes Simplex, run by University of Washington at 1 site in Peru.
Trial summary
Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that that HSV is an important cofactor in HIV transmission. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- HIV Infection, Herpes Simplex, Sexually Transmitted Diseases
- What is being tested?
- valacyclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 sitePeru
- Study dates
- Aug 2003to Jul 2004
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Greater than 18 years old,
- Documented HIV-1 seropositive,
- CD4 count greater than 200,
- Not on HIV antiretroviral therapy,
- HSV-2 seropositive as determined by Focus EIA (IN >3.5)
- Not intending to move out of the area for the duration of study participation.
- Willing and able to:provide independent written informed consent;undergo clinical evaluations;take study drug as directed;adhere to follow-up schedule.
- Bacterial STDs (symptomatic STD syndromes or laboratory-confirmed asymptomatic gonorrhea and syphilis) are treated within two weeks of study enrollment and random assignment.
Who cannot join
- MSM who meet any of the following criteria are not eligible for this study:
- Known history of adverse reaction to valacyclovir, acyclovir or famciclovir;
- Planned open label use of acyclovir, valacyclovir, or famciclovir
- Known medical history of seizures
- Known renal failure, serum creatinine >2.0mg/dl
- Hematocrit < 30 %
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Double-blind, Placebo-controlled Crossover Trial of Valacyclovir for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Coinfected Men Who Have Sex With Men (MSM).
Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that that HSV is an important cofactor in HIV transmission.
The trial's purpose is to assess the reduction in HIV shedding associated with valacyclovir for suppression of HSV-2 reactivation.
This proof-of-concept, randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected men, assessed the effects of daily valacyclovir on HIV-1 levels in the plasma and rectal mucosa secretions.
Read the detailed description
Herpes simplex virus type 2 (HSV-2) is common among HIV infected persons. HSV-2 reactivation is associated with increased plasma and genital HIV-1 levels, and in vitro, HSV-2 upregulates HIV transcription.
The trial assessed whether HSV-2 suppression reduces rectal and plasma HIV-1 levels in HIV-1, HSV-2 co-infected men who have sex with men (MSM).
Conducted in Lima Peru, 20 antiretroviral naive HIV-1 and HSV-2 seropositive MSM with CD4 >200 were randomly assigned to receive valacyclovir 500 mg bid or placebo for 8 weeks, than a 2 week washout period, followed by the alternative regimen for 8 weeks. Men collected daily home anogenital swabs for HSV DNA PCR, had three weekly anoscopy procedures for collection of rectal mucosal secretions for HIV-1 RNA, HSV DNA, and weekly plasma HIV-1 RNA by PCR. Outcomes were plasma and rectal HIV-1 levels by study arm.
- Conditions
- HIV Infection, Herpes Simplex, Sexually Transmitted Diseases
- Being tested
- valacyclovir, matching placebo
- Keywords
- HIV infection, HIV shedding, HSV suppression, Co-infected, MSM, Reactivation, Valacyclovir
- Medical subject headings
- HIV Infections, Herpes Simplex, Sexually Transmitted Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
valacyclovirDrug
500 mg twice-daily oral
matching placeboDrug
twice daily as per experimental drug
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: valacyclovir |
| 2 | Placebo comparator | Not described Receives: Drug: matching placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation.
Measured: 18 weeks
Secondary outcomes (3)
Evaluate HSV-2 suppression with decreased plasma HIV RNA levels
Measured: 18 weeks
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals
Measured: 18 weeks
Determine the temporal pattern of HIV shedding in the rectum, pharynx and semen with respect to mucosal HSV-1 and HSV-2 reactivation; Determine HSV-2 suppression and HIV replication within rectal mucosa.
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2006 (estimated)
- Study startAug 2003
- Study completionJul 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Collaborators
- GlaxoSmithKline, Asociación Civil Impacta Salud y Educación, Peru
- Investigators
- Connie Celum, MD, MPH, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00378976
- Sponsor's protocol ID
- 21760-A
- Other IDs
- AI277S7;AI38858;AI30731
- Status last verified
- Aug 2013
- First submitted
- 19 Sep 2006
- Last updated
- 22 Aug 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Magaret A, Wald A, Corey L, Celum C. HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men. AIDS. 2009 Feb 20;23(4):479-83. doi: 10.1097/QAD.0b013e328326ca62.
PubMed 19169140Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Zuniga R, Magaret AS, Wald A, Corey L, Celum C. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis. 2007 Nov 15;196(10):1500-8. doi: 10.1086/522523. Epub 2007 Oct 31.
PubMed 18008230
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled Crossover Trial of Valacyclovir for Suppression of HSV and HIV Shedding in HIV-1, HSV-2 Coinfected Men Who Have Sex With Men (MSM).
- ClinicalTrials.gov ID
- NCT00378976
- Acronym / sponsor ID
- 21760-A
- Conditions
- HIV Infection, Herpes Simplex, Sexually Transmitted Diseases
- Keywords
- HIV infection, HIV shedding, HSV suppression, Co-infected, MSM, Reactivation, Valacyclovir
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Collaborators
- GlaxoSmithKline, Asociación Civil Impacta Salud y Educación, Peru
- Study start
- Aug 2003
- Study completion
- Jul 2004 (actual)
- First posted
- 21 Sep 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Over 80% of HIV-1 infected persons are also seropositive for HSV-2. Increasingly, clinical and epidemiologic evidence show the role of HSV in increasing HIV infectiousness. The evidence suggests that that HSV is an important cofactor in HIV transmission.
The trial's purpose is to assess the reduction in HIV shedding associated with valacyclovir for suppression of HSV-2 reactivation.
This proof-of-concept, randomized, double-blind, placebo controlled crossover trial of 20 HIV/HSV-2 co-infected men, assessed the effects of daily valacyclovir on HIV-1 levels in the plasma and rectal mucosa secretions.
Detailed description
Herpes simplex virus type 2 (HSV-2) is common among HIV infected persons. HSV-2 reactivation is associated with increased plasma and genital HIV-1 levels, and in vitro, HSV-2 upregulates HIV transcription.
The trial assessed whether HSV-2 suppression reduces rectal and plasma HIV-1 levels in HIV-1, HSV-2 co-infected men who have sex with men (MSM).
Conducted in Lima Peru, 20 antiretroviral naive HIV-1 and HSV-2 seropositive MSM with CD4 >200 were randomly assigned to receive valacyclovir 500 mg bid or placebo for 8 weeks, than a 2 week washout period, followed by the alternative regimen for 8 weeks. Men collected daily home anogenital swabs for HSV DNA PCR, had three weekly anoscopy procedures for collection of rectal mucosal secretions for HIV-1 RNA, HSV DNA, and weekly plasma HIV-1 RNA by PCR. Outcomes were plasma and rectal HIV-1 levels by study arm.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: valacyclovir |
| 2 | Placebo comparator | Drug: matching placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Greater than 18 years old,
- Documented HIV-1 seropositive,
- CD4 count greater than 200,
- Not on HIV antiretroviral therapy,
- HSV-2 seropositive as determined by Focus EIA (IN >3.5)
Key exclusion criteria (6 listed)
- Known history of adverse reaction to valacyclovir, acyclovir or famciclovir;
- Planned open label use of acyclovir, valacyclovir, or famciclovir
- Known medical history of seizures
- Known renal failure, serum creatinine >2.0mg/dl
- Hematocrit < 30 %
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| valacyclovir500 mg twice-daily oral | Drug | 1 |
| matching placebotwice daily as per experimental drug | Drug | 2 |
Primary outcome
Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation.
Time frame: 18 weeks
3 secondary outcomes
Evaluate HSV-2 suppression with decreased plasma HIV RNA levels
Time frame: 18 weeks
Assess the effect of daily valacyclovir on pharyngeal shedding in HSV-1 seropositive individuals
Time frame: 18 weeks
Determine the temporal pattern of HIV shedding in the rectum, pharynx and semen with respect to mucosal HSV-1 and HSV-2 reactivation; Determine HSV-2 suppression and HIV replication within rectal mucosa.
Time frame: 18 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2013.
- Derived from this study: PubMed 19169140Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Magaret A, Wald A, Corey L, Celum C. HSV suppression reduces seminal HIV-1 levels in HIV-1/HSV-2 co-infected men who have sex with men. AIDS. 2009 Feb 20;23(4):479-83. doi: 10.1097/QAD.0b013e328326ca62.
- Derived from this study: PubMed 18008230Zuckerman RA, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, Zuniga R, Magaret AS, Wald A, Corey L, Celum C. Herpes simplex virus (HSV) suppression with valacyclovir reduces rectal and blood plasma HIV-1 levels in HIV-1/HSV-2-seropositive men: a randomized, double-blind, placebo-controlled crossover trial. J Infect Dis. 2007 Nov 15;196(10):1500-8. doi: 10.1086/522523. Epub 2007 Oct 31.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Connie Celum, MD, MPH principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing valacyclovir in people with HIV Infection and Herpes Simplex, run by University of Washington at 1 site in Peru.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Peru. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in anogenital HIV-1 shedding with suppression of HSV-2 reactivation. (time frame: 18 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00378976, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2013.