Herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus type 1 (HIV-1) co-infection Infections and Infestations Human immunodeficiency virus [HIV] disease resulting in infectious and parasitic diseases
Conditions
Interventions
Patients in the intervention group will receive oral valaciclovir 500 mg twice daily, the standard dose used for HSV-2 suppression in HIV-infected individuals. Individuals in the control arm will rece
Sponsors
University Health Network (UHN) (Canada)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 17/12/2012: 1. Adult (aged 18 years or older or as per Local/Provincial Guidelines), either sex, with documented HIV-1 infection 2. Documented HIV-1 infection (determined by EIA and Western blot) 3. No use of chronic anti-HSV therapy for the past 6 months, and not anticipated to require chronic anti-HSV therapy during the study 4. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure) 5. 5. CD4 count within the 400-900 cells/mm3 range (inclusive) on two consecutive occasions, with at least one measurement within 30 days of initiating trial (baseline visit) 6. Does not meet recommendations for initiating ARV therapy according to current guidelines Initial inclusion criteria at the time of registration: 1. Adults aged over 18 years, either sex, with documented HIV-1 infection 2. Documented HSV-2 seropositivity 3. Maximum of two episodes recurrent symptomatic HSV recurrences per year by self-report 4. Neither currently using nor anticipated to require chronic anti-HSV therapy during the study 5. Anti-retroviral naive (no more than 14 days of total prior anti-retroviral [ARV] exposure) 6. CD4 count within the 400 - 900 cells/mm^3 range (inclusive) on two consecutive occasions, with at least one measurement within 4 weeks of initiating trial 7. Does not meet recommendations for initiating ARV therapy according to current guidelines
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 17/12/2012: 1. Pregnant or actively planning to become pregnant 2. Receiving chemotherapy, chronic steroid therapy or other immunomodulatory medications (e.g. interferon, azathioprine, methotrexate, TNF-alpha antagonists, etc.) 3. Have an estimated creatinine clearance less than 30 ml/min 4. Have another medical condition likely to cause death within 24 months 5. Enrolled in a therapeutic HIV vaccine or immunotherapy trial 6. Enrolled in another trial investigating the impact of another intervention on HIV disease progression 7. HIV elite controller (EC), phenotypically defined here as documented duration of HIV infection of =5 years, a persistent CD4 cell count =500 cells/mm3, and a persistent plasma HIV viral load of <1000 copies/mL in the absence of antiretroviral therapy Initial exclusion criteria at the time of registration: 1. Pregnant 2. Receiving chemotherapy or chronic steroid therapy 3. Have an estimated creatinine clearance less than 30 ml/min 4. Have an active opportunistic infection 5. Have another medical condition likely to cause death within 24 months 6. Enrolled in a therapeutic vaccine or immunotherapy trial 7. Enrolled in another trial investigating the impact of another intervention on HIV disease progression 8. Fit the phenotype of an HIV elite controller (EC), since the natural history of HIV infection is fundamentally different in such individuals
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| As or 17/12/2012 primary outcome changed to: Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time. Initial primary outcome measure: Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Annual rate of change in CD4 count, calculated as the slope of patients' CD4 count change/time 2. Annual rate of change in the CD4 cell count percentage, calculated as the slope of the patient's CD4 count percentage change over time 3. Log^10 plasma HIV viral load at 12, 24 and 36 months of follow-up 4. Treatment-emergent adverse events and laboratory abnormalities (complete blood count [CBC], plasma creatinine, blood urea nitrogen, alanine transaminase, aspartate transaminase, total bilirubin, amylase, international normalised ratio, partial thromboplastin time) 5. Frequency of episodes of HSV reactivations at any anatomic site 6. Proportion of microbiologically confirmed flares of HSV during the trial that are caused by laboratory-confirmed aciclovir-resistant HSV Added 18/08/2009: 7. Quality of life As of 17/12/2012 the first secondary outcome changed to: Time from baseline until reaching the primary endpoint: a composite of either a CD4 cell count less than or equal to 350 cells/mm^3 measured on two consecutive occasions at least 1 month apart, or initiation of HAART for any reason, whichever occurs first. | — |
Countries
Argentina, Brazil, Canada
Outcome results
None listed