HIV Infection, HSV Infection
Conditions
Keywords
HSV, HIV
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.
Interventions
DRUGacyclovir
acyclovir 400 mg orally, twice daily for 12 weeks
DRUGvalacyclovir
valacyclovir 1.5 g orally, twice daily, for 12 weeks
Sponsors
University of Washington
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. | 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. |
Secondary
| Measure | Time frame |
|---|---|
| Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons. | 28 weeks |
Countries
Kenya
Participant flow
Recruitment details
HSV-2/HIV-1 dually-infected participants were recruited between March and November 2010 from Thika, Kenya.
Pre-assignment details
66 participants screened; 34 excluded (33 did not meet inclusion criteria, 1 declined study participation); 32 enrolled
Participants by arm
| Arm | Count |
|---|---|
| Acyclovir Then Valacyclovir acyclovir 400 mg orally twice daily for 12 weeks, 2 week washout, then valacyclovir 1.5 g orally twice daily for 12 weeks | 18 |
| Valacyclovir Then Acyclovir valacyclovir 1.5 g orally twice daily for 12 weeks, 2 week washout, then acyclovir 400 mg orally twice daily for 12 weeks | 14 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Second Intervention | Pregnancy | 1 | 1 |
Baseline characteristics
| Characteristic | Acyclovir Then Valacyclovir | Valacyclovir Then Acyclovir | Total |
|---|---|---|---|
| Age, Customized <=18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized >=65 years | 0 participants | 0 participants | 0 participants |
| Age, Customized Between 18 and 65 years | 18 participants | 14 participants | 32 participants |
| Plasma HIV-1 RNA Level at Enrollment | 4.05 log10 copies/mL STANDARD_DEVIATION 0.72 | 4.08 log10 copies/mL STANDARD_DEVIATION 0.85 | 4.07 log10 copies/mL STANDARD_DEVIATION 0.75 |
| Region of Enrollment Kenya | 18 participants | 14 participants | 32 participants |
| Sex: Female, Male Female | 11 Participants | 7 Participants | 18 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 31 |
| serious Total, serious adverse events | 0 / 32 | 0 / 31 |
Outcome results
Primary
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.
Time frame: Weekly for 12 weeks per intervention
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Acyclovir | Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. | 3.56 log10 copies/mL |
| Valacyclovir | Mean Level of HIV-1 RNA in Plasma of Participants While on Acyclovir or Valacyclovir. | 2.94 log10 copies/mL |
Secondary
Safety of Valacyclovir 1.5 Gram Orally Twice Daily in HIV-1 Seropositive Persons.
Time frame: 28 weeks