HSV InfectionPhase 4ACV-VALNCT01026454
Valacyclovir vs. Acyclovir as HSV-2 Suppressive Therapy: Effect on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons
A Phase 4 study testing acyclovir and valacyclovir in people with HSV Infection and HIV Infection, run by University of Washington at 1 site in Kenya.
Trial summary
The purpose of this study is to determine whether treating HSV-2 with either valacyclovir or acyclovir is more effective in suppressing HIV-1 virus levels in people co-infected with HIV-1 and HSV-2. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HSV Infection, HIV Infection
- What is being tested?
- acyclovir and valacyclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteKenya
- Study dates
- Feb 2010to Dec 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV-1 seropositive
- Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
- CD4 cell count >250 cell/µL
- Not otherwise eligible for antiretroviral therapy according to Uganda national guidelines
- Detectable HIV-1 plasma viral load
- HSV-2 seropositive
- Not intending to move out of the area for the duration of study participation.
- Able to participate in the study at the Partners in Prevention site in Thika, Kenya
Who cannot join
- Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir.
- Planned use of acyclovir, valacyclovir, or famciclovir
- Use of ganciclovir, foscarnet, or cidofovir
- Known medical history of seizures
- Serum creatinine >1.5 mg/dL
- AST or ALT >3 times upper limit of normal
Show all 13Show fewer
- Hematocrit <30 %
- Absolute neutrophil count <1000
- Platelet count <75,000
- History of thrombotic microangiopathy
- Any other condition which, in the opinion of the principal investigator, may compromise the ability to follow study procedures and complete the study
- Participation in another HIV therapeutics trial
- For women, pregnancy as confirmed by a urine pregnancy test
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label, Crossover Trial of the Effect of High-dose Daily HSV-2 Suppressive Therapy on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons
The purpose of this study is to determine whether treating HSV-2 with either valacyclovir or acyclovir is more effective in suppressing HIV-1 virus levels in people co-infected with HIV-1 and HSV-2.
Read the detailed description
Sexual transmission is responsible for the vast majority of HIV-1 infections among adults worldwide. In sub-Saharan Africa, the region hardest hit by the HIV-1 epidemic, HSV-2 prevalences of 30-50% have been seen in the general population with prevalence up to 90% in infected with HIV-1. HSV-2 is common in those with, or at risk for, HIV-1 infection, and HSV-2 reactivation increases HIV-1 acquisition and infectiousness. Recent studies have shown that suppression of HSV-2 has a sustained effect on lowering HIV-1 levels in blood plasma. New data have raised the question whether higher doses of HSV-2 suppressive therapy might be more effective at suppressing HIV-1 levels. Acyclovir and valacyclovir, chosen for use in this study, are safe and effective treatments for decreasing the frequency of HSV-2 reactivation and shedding. The standard dose of acyclovir is 400 mg twice a day. Valacyclovir, a drug that converts to acyclovir after absorption, delivers higher concentrations of acyclovir. 1.5 grams of valacyclovir, will be used to provide a higher dose of acyclovir, and will be compared with the standard dose of 400 mg twice a day of acyclovir.
- Conditions
- HSV Infection, HIV Infection
- Being tested
- acyclovir, valacyclovir
- Keywords
- HSV, HIV
- Medical subject headings
- Herpes Simplex, HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
acyclovirDrug
acyclovir 400 mg orally, twice daily for 12 weeks
valacyclovirDrug
valacyclovir 1.5 g orally, twice daily, for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| acyclovir | Active comparator | acyclovir 400 mg orally twice daily Receives: Drug: acyclovir |
| valacyclovir | Active comparator | valacyclovir 1.5 g orally twice daily Receives: Drug: valacyclovir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir.
Mean level of HIV-1 RNA in plasma of participants while on 400 mg twice daily of acyclovir versus while on 1.5 g twice daily of valacyclovir.
Measured: Weekly for 12 weeks per intervention
Secondary outcomes (1)
Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.
Measured: 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Dec 2009 (estimated)
- Study startFeb 2010
- Primary completionNov 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for HSV 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Connie Celum, University of Washington
- Investigators
- Connie Celum, MD, MPH, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01026454
- Sponsor's protocol ID
- 37162-A
- Acronym
- ACV-VAL
- Status last verified
- Mar 2014
- First submitted
- 2 Dec 2009
- Last updated
- 8 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Brown EL, Wald A, Hughes JP, Morrow RA, Krantz E, Mayer K, Buchbinder S, Koblin B, Celum C. High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study. Am J Epidemiol. 2006 Oct 15;164(8):733-41. doi: 10.1093/aje/kwj270. Epub 2006 Aug 8.
PubMed 16896053Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006 Jan 2;20(1):73-83. doi: 10.1097/01.aids.0000198081.09337.a7.
PubMed 16327322Schacker T, Zeh J, Hu H, Shaughnessy M, Corey L. Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression. J Infect Dis. 2002 Dec 15;186(12):1718-25. doi: 10.1086/345771. Epub 2002 Nov 22.
PubMed 12447756Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011 Dec 15;204(12):1912-7. doi: 10.1093/infdis/jir649. Epub 2011 Oct 12.
PubMed 21998479
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Crossover Trial of the Effect of High-dose Daily HSV-2 Suppressive Therapy on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons
- ClinicalTrials.gov ID
- NCT01026454
- Acronym / sponsor ID
- ACV-VAL / 37162-A
- Conditions
- HSV Infection, HIV Infection
- Keywords
- HSV, HIV
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- Feb 2010
- Primary completion
- Nov 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 4 Dec 2009 (estimated)
- Results
- Posted 5 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether treating HSV-2 with either valacyclovir or acyclovir is more effective in suppressing HIV-1 virus levels in people co-infected with HIV-1 and HSV-2.
Detailed description
Sexual transmission is responsible for the vast majority of HIV-1 infections among adults worldwide. In sub-Saharan Africa, the region hardest hit by the HIV-1 epidemic, HSV-2 prevalences of 30-50% have been seen in the general population with prevalence up to 90% in infected with HIV-1. HSV-2 is common in those with, or at risk for, HIV-1 infection, and HSV-2 reactivation increases HIV-1 acquisition and infectiousness. Recent studies have shown that suppression of HSV-2 has a sustained effect on lowering HIV-1 levels in blood plasma. New data have raised the question whether higher doses of HSV-2 suppressive therapy might be more effective at suppressing HIV-1 levels. Acyclovir and valacyclovir, chosen for use in this study, are safe and effective treatments for decreasing the frequency of HSV-2 reactivation and shedding. The standard dose of acyclovir is 400 mg twice a day. Valacyclovir, a drug that converts to acyclovir after absorption, delivers higher concentrations of acyclovir. 1.5 grams of valacyclovir, will be used to provide a higher dose of acyclovir, and will be compared with the standard dose of 400 mg twice a day of acyclovir.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| acyclovir | Active comparator | Drug: acycloviracyclovir 400 mg orally twice daily |
| valacyclovir | Active comparator | Drug: valacyclovirvalacyclovir 1.5 g orally twice daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- HIV-1 seropositive
- Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
- CD4 cell count >250 cell/µL
- Not otherwise eligible for antiretroviral therapy according to Uganda national guidelines
- Detectable HIV-1 plasma viral load
Key exclusion criteria (13 listed)
- Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir.
- Planned use of acyclovir, valacyclovir, or famciclovir
- Use of ganciclovir, foscarnet, or cidofovir
- Known medical history of seizures
- Serum creatinine >1.5 mg/dL
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 |
|---|---|---|
| acycloviracyclovir 400 mg orally, twice daily for 12 weeks | Drug | acyclovir |
| valacyclovirvalacyclovir 1.5 g orally, twice daily, for 12 weeks | Drug | valacyclovir |
Primary outcome
Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir.
Time frame: Weekly for 12 weeks per intervention
Mean level of HIV-1 RNA in plasma of participants while on 400 mg twice daily of acyclovir versus while on 1.5 g twice daily of valacyclovir.
1 secondary outcome
Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.
Time frame: 28 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16896053Brown EL, Wald A, Hughes JP, Morrow RA, Krantz E, Mayer K, Buchbinder S, Koblin B, Celum C. High risk of human immunodeficiency virus in men who have sex with men with herpes simplex virus type 2 in the EXPLORE study. Am J Epidemiol. 2006 Oct 15;164(8):733-41. doi: 10.1093/aje/kwj270. Epub 2006 Aug 8.
- Background: PubMed 16327322Freeman EE, Weiss HA, Glynn JR, Cross PL, Whitworth JA, Hayes RJ. Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2006 Jan 2;20(1):73-83. doi: 10.1097/01.aids.0000198081.09337.a7.
- Background: PubMed 12447756Schacker T, Zeh J, Hu H, Shaughnessy M, Corey L. Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression. J Infect Dis. 2002 Dec 15;186(12):1718-25. doi: 10.1086/345771. Epub 2002 Nov 22.
- Derived from this study: PubMed 21998479Mugwanya K, Baeten JM, Mugo NR, Irungu E, Ngure K, Celum C. High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial. J Infect Dis. 2011 Dec 15;204(12):1912-7. doi: 10.1093/infdis/jir649. Epub 2011 Oct 12.
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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 4 study testing acyclovir and valacyclovir in people with HSV Infection and HIV Infection, run by University of Washington at 1 site in Kenya.
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 13 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 8 Apr 2014. 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 Kenya. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Mar 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. (time frame: Weekly for 12 weeks per intervention). 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 NCT01026454, which also lists 4 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 8 Apr 2014.