Clinical trial NCT01026454: Valacyclovir vs. Acyclovir as HSV-2 Suppressive Therapy: Effect on Plasma HIV-1 Levels Among HIV-1/HSV-2 Co-infected Persons
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HSV Infection
HIV Infection
Keywords: HSV
HIV
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2009-12-04
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* 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

Primary outcomes:
measure: Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir.
timeFrame: Weekly for 12 weeks per intervention
Secondary outcomes:
measure: Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.
timeFrame: 28 weeks
Other outcomes:
Locations:
city: Thika
country: Kenya
facility: Thika Partners in Prevention
Study officials:
affiliation: University of Washington
name: Connie Celum, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Freeman 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.
citation: Schacker 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.
citation: Mugwanya 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.