HIV, HIV Infections
Conditions
Keywords
HSV-2, Herpes Simplex, HSV Type 2, HIV, HIV/HSV, treatment experienced
Brief summary
The purpose of the study is to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.
Detailed description
Most people with herpes infections do not know they have the infection. HSV infections most often occur in areas in and around the mouth and genital tract. HSV Type 1 (HSV-1) usually causes cold sores or fever blisters and HSV Type 2 (HSV-2) usually causes lesions in the genital or rectal areas. However, HSV-1 can sometimes cause genital herpes and HSV-2 can cause oral lesions (acquired from oral-genital sex). Herpes Simplex is transmitted by contact with someone who is shedding virus in either the mouth or genital tract, usually by kissing or sexual intercourse. While contact with an active sore can cause transmission, so can contact with saliva or genital secretions that are infected, even when the person does not have an obvious sore. This is called asymptomatic shedding of HSV. Once acquired, the virus has the ability to remain inactive in the nervous system in the area of the mouth or genital region. Persons with both HIV and HSV-2 often have shedding of both viruses. We know that persons with HSV-2 tend to have increased amounts of HIV in their blood as well. Recently, research studies have found that taking medicine daily to prevent asymptomatic HSV-2 shedding can reduce the amount of HIV found in the blood and in genital secretions. This study seeks to determine how common herpes is among persons with HIV who do not know they have it and if valacyclovir (FDA approved drug) reduces outbreaks of herpes, the amount of HIV in the blood, and the amount of HSV in bodily secretions.
Interventions
DRUGValacyclovir
500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks
DRUGPlacebo
Dosage: Two tablets once a day for 24 weeks
Sponsors
GlaxoSmithKline
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* 19 years or older * HSV-2 (Herpes simplex virus type 2) seropositive as determined by HerpeSelect-2 ELISA * Documented HIV-1 seropositive * Currently receiving HAART for 3 months or longer * CD4 (cluster of differentiation 4) count 350 or greater * Women of child bearing potential must agree to use acceptable contraceptive measures during the entire conduct of the study. Acceptable contraceptive methods include one or more of the following: oral hormonal contraceptives, injectable hormonal contraceptives, transdermal hormonal contraceptives, IUD (intrauterine device), diaphragm or cervical cap. * Willing and able to provide written informed consent, undergo clinical evaluations, and take study drug as directed
Exclusion criteria
* History of symptomatic genital herpes, lesions or symptoms consistent with genital herpes, or recurrent undiagnosed symptoms consistent with genital herpes. * Known history of adverse reaction to acyclovir, valacyclovir, or famciclovir. * Planned open label use of acyclovir, valacyclovir, ganciclovir, valganciclovir, famciclovir, cidofovir, or foscarnet for oral herpes or other herpes viral infections. * Medical history of seizures * Renal insufficiency, defined as serum creatinine greater than 1.5 mg/dl * AST (aspartate aminotransferase) or ALT (alanine aminotransferase) over 5 times uper limit of normal * History of thrombotic microangiopathy * For women, pregnancy as confirmed by a urine or serum pregnancy test. * Any other condition which, in the opinion of the principal investigator, may compromise the subject's ability to follow study procedures and complete the study. * Participants with active bacterial STDs (sexually transmitted diseases) may be treated and be eligible for enrollment 14 days after STD therapy is discontinued and symptoms have resolved.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Herpes Simplex Virus Type 2 Recurrence | 24 Weeks | Number of recurrences of genital herpes |
| CD4 Count | 24 weeks | CD4 count as measured after 24 weeks of placebo versus valacyclovir. Reports as cells/ml |
| Number of Participants With an HIV Viral Load of <500 Copies/ml | 24 weeks | Number of participants with an HIV Viral Load of \<500 copies/ml at 24 weeks |
| Rate of Asymptomatic HSV-2 Genital Shedding | 24 weeks | Proportion of days on which HSV shedding was observed. This part of the study was performed in a subset of participants (N = 34). Participant collected daily genital specimens for 8 weeks starting at week 16 and continuing through week 24 of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Valacyclovir Valacyclovir: 500 mg tablets. Dosage two tablets (1000 mg)once daily for 24 weeks | 45 |
| Placebo Placebo: Dosage: Two tablets once a day for 24 weeks | 22 |
| Total | 67 |
Baseline characteristics
| Characteristic | Total | Placebo | Valacyclovir |
|---|---|---|---|
| Absolute CD4 (cluster of differentiation 4) Count | 582 cell/ml | 693 cell/ml | 528 cell/ml |
| Age, Continuous | 45 years | 43 years | 45 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 22 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number with Undetectable Viral Load | 59 participants | 19 participants | 40 participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 34 Participants | 9 Participants | 25 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 33 Participants | 13 Participants | 20 Participants |
| Region of Enrollment United States | 67 participants | 22 participants | 45 participants |
| Sex: Female, Male Female | 9 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 58 Participants | 21 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 0 / 22 |
| other Total, other adverse events | 0 / 45 | 0 / 22 |
| serious Total, serious adverse events | 0 / 45 | 0 / 22 |
Outcome results
Primary
CD4 Count
CD4 count as measured after 24 weeks of placebo versus valacyclovir. Reports as cells/ml
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Valacyclovir | CD4 Count | 536 cells/ml |
| Placebo | CD4 Count | 627.5 cells/ml |
Primary
Herpes Simplex Virus Type 2 Recurrence
Number of recurrences of genital herpes
Time frame: 24 Weeks
Population: No participants reported genital herpes recurrence during the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valacyclovir | Herpes Simplex Virus Type 2 Recurrence | 0 Recurrence |
| Placebo | Herpes Simplex Virus Type 2 Recurrence | 0 Recurrence |
Primary
Number of Participants With an HIV Viral Load of <500 Copies/ml
Number of participants with an HIV Viral Load of \<500 copies/ml at 24 weeks
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valacyclovir | Number of Participants With an HIV Viral Load of <500 Copies/ml | 38 Participants |
| Placebo | Number of Participants With an HIV Viral Load of <500 Copies/ml | 20 Participants |
Primary
Rate of Asymptomatic HSV-2 Genital Shedding
Proportion of days on which HSV shedding was observed. This part of the study was performed in a subset of participants (N = 34). Participant collected daily genital specimens for 8 weeks starting at week 16 and continuing through week 24 of the study.
Time frame: 24 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Valacyclovir | Rate of Asymptomatic HSV-2 Genital Shedding | 0.0009 Proportion of days |
| Placebo | Rate of Asymptomatic HSV-2 Genital Shedding | 0.0001 Proportion of days |