Trial to Study the Effect of Dose of Herpes Simplex Virus-2 (HSV-2) Suppressive Therapy on HSV and HIV

University of Washington

Status and phase

Completed

Phase 4

Conditions

HIV Infection

Genital Herpes

Treatments

Drug: acyclovir

Drug: valacyclovir

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00527618

31203

GSK VAL111009 - VAL140 (Other Grant/Funding Number)

Details and patient eligibility

About

To compare the effect of high-dose valacyclovir (1 gram orally twice daily) versus standard-dose acyclovir (400 mg orally twice daily) on the frequency of genital HSV reactivation and on plasma HIV-1 levels among HSV-2/HIV-1 co-infected individuals. The investigators hypothesize that high-dose valacyclovir will result in greater reduction in plasma HIV-1 and genital HSV reactivation.

Full description

We propose to conduct a randomized, open-label, cross-over study of 38 individuals who are HIV-1 seropositive and HSV-2 seropositive. Both men and women will be recruited for the study. Participants must not be on antiretroviral therapy and must not be planning to initiate antiretroviral therapy during the anticipated study period. Participants will be randomized 1:1 to receive acyclovir 400 mg twice daily or valacyclovir 1000 mg twice daily. After 12 weeks on the initial treatment, each participant will be crossed over to the alternative treatment arm for 12 weeks. The treatment periods will be separated by a 2-week washout period. During the first four weeks of each treatment period (i.e. weeks 1-4 and weeks 15-18), participants will provide self-collected genital swabs daily for HSV DNA quantification. Each week during the entire study period plasma samples will be collected from participants for HIV-1 RNA quantification.

Open-label acyclovir and valacyclovir will be used for this trial, as the primary outcome measures (genital HSV and plasma HIV-1) are unlikely to be influenced by knowledge of treatment assignment. However, laboratory staff performing plasma HIV-1 and genital HSV measurements will not be aware of treatment assignment.

Optional Sub-Study A: Sub-study A will be offered to study participants. The purpose of sub-study A is to measure the effect of valacyclovir twice daily on plasma HIV-1 replication.

Enrollment

28 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 18 years or older
Documented HIV-1 seropositive
Not on HIV-1 antiretroviral therapy nor planning to initiate antiretroviral therapy during the study period
Detectable HIV-1 plasma viral load
HSV-2 seropositive as determined by western blot
Not intending to move out of the area for the duration of study participation
Willing and able to provide independent written informed consent
Willing and able to undergo clinical evaluations
Willing and able to take study drug as directed
Willing and able to adhere to follow-up schedule

Exclusion criteria

Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir
Planned open label use of acyclovir, valacyclovir, or famciclovir
History of evidence of CMV disease
Known medical history of seizures
Known renal insufficiency, defined as serum creatinine greater than 1.5 mg/dl
AST or ALT greater than 3 times upper limit of normal
Hematocrit less than 30 %
Neutropenia, defined as absolute neutrophil count less than 1000
Thrombocytopenia, defined as platelet count less than 75,000
History of thrombotic microangiopathy
For women, pregnancy as confirmed by a urine pregnancy test
Any other condition which, in the opinion of the principal investigator, may compromise the ability to follow study procedures and complete the study