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VIP: HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT00530777
Collaborator
Royalty Research Fund - University of Washington (Other), Puget Sound Partners for Global Health (Other), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
148
Enrollment
1
Location
2
Arms
28
Duration (Months)
5.3
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

In this study, we will determine whether treating pregnant and breastfeeding women co-infected with human immunodeficiency virus type 1 (HIV-1) and herpes simplex virus type 2 (HSV-2) with daily valacyclovir will reduce HIV-1 levels in plasma, genital, and breast milk and will decrease the risk of mother-to-child HIV-1 transmission (MTCT).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Each year over 500,000 children become HIV-1-infected in sub-Saharan Africa after exposure to maternal virus in blood, genital secretions, and breast milk. Identifying feasible, safe, and affordable interventions that prevent mother-to-child transmission remains a priority for HIV-1 prevention research. Interventions to reduce breast milk HIV-1 transmission are lacking and most urgently needed.

We propose a randomized clinical trial to determine whether incorporating HSV-2 suppression with valacyclovir into standard prevention of mother-to-child HIV-1 transmission regimens will reduce plasma, cervical, and breast milk HIV-1 RNA levels and risk of transmission among HIV-1-infected and HSV-2-seropositive women. We plan to enroll a total of 148 HIV-1 and HSV-2 co-infected pregnant women with CD4>200 cells/μl who seek antenatal care prior to 32 weeks gestation at a clinic in Nairobi, Kenya. Women will be randomized to receive either valacyclovir suppressive therapy or placebo at 34 weeks gestation and mother-infant pairs will be followed for 12 months postpartum. Follow-up visits will be scheduled at 38 weeks gestation; birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months postpartum. Maternal blood, genital, and breast milk specimens obtained at follow-up visits will be used to determine the effect of valacyclovir suppressive therapy on plasma and breast milk HIV-1 RNA levels. Infant filter paper specimens for HIV-1 DNA assays will be collected at birth; 2, 6, 10 and 14 weeks; and 6, 9, and 12 months in order to compare the proportion of infants acquiring HIV-1 by 12 months in the two study arms and determine the timing of HIV-1 infection. In addition, we will monitor maternal and infant renal function in preparation for a larger randomized clinical trial in Africa. The results of this study will help guide the design of a multi-site clinical trial with adequate power to determine the effect of HSV-2 suppression on vertical (MTCT) transmission of HIV-1 infection.

Study Design

Study Type:
Interventional
Actual Enrollment :
148 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
HSV-2 Suppression to Reduce Maternal HIV-1 RNA Levels During Pregnancy and Breastfeeding
Study Start Date :
Apr 1, 2008
Actual Primary Completion Date :
Aug 1, 2010
Actual Study Completion Date :
Aug 1, 2010

Arms and Interventions

Arm Intervention/Treatment
Experimental: 1

500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum

Drug: valacyclovir
500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum
Other Names:
  • Valtrex

    		•
    Placebo Comparator: 2

    oral placebo twice daily from 34 weeks gestation to 1 year postpartum

    Drug: placebo
    oral placebo twice daily from 34 weeks gestation to 1 year postpartum

    Outcome Measures

    Primary Outcome Measures

    1. Mean Change in HIV-1 Levels in Plasma Between 34 and 38 Weeks Gestation [4 weeks]

      Calculated as log10 plasma viral load at 34 weeks gestation - log10 plasma viral load at 38 weeks gestation

    Secondary Outcome Measures

    1. Vertical HIV-1 Transmission [1 year postpartum]

      Mother-to-child HIV transmission

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • HIV-1 seropositive

    • HSV-2 seropositive

    • Plans to deliver in Nairobi

    • Resides and plans to remain in Nairobi for 12 months postpartum

    • 18 years of age or older

    • CD4 count>250 cells/μl

    Exclusion Criteria:

    • indication for highly active antiretroviral therapy (e.g., WHO stage III or IV)

    • hypersensitivity to valacyclovir or acyclovir

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mathare North City Clinic Nairobi Kenya

    Sponsors and Collaborators

    • University of Washington
    • Royalty Research Fund - University of Washington
    • Puget Sound Partners for Global Health
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

    Investigators

    • Principal Investigator: Carey Farquhar, MD, MPH, University of Washington

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Carey Farquhar, Associate Professor, University of Washington
    ClinicalTrials.gov Identifier:
    NCT00530777
    Other Study ID Numbers:
    • 32462
    • 07-7306-A01
    • R03HD057773
    First Posted:
    Sep 17, 2007
    Last Update Posted:
    Dec 19, 2018
    Last Verified:
    Nov 1, 2018
    Keywords provided by Carey Farquhar, Associate Professor, University of Washington
    Disease Transmission, Vertical
    valacyclovir
    Randomized Controlled Trials
    HIV
    herpes
    Herpesvirus 2, Human
    HIV Seronegativity
    Additional relevant MeSH terms:
    Herpes Simplex
    Valacyclovir

    Study Results

    Participant Flow

    Recruitment Details HIV-1 infected pregnant women seeking antenatal care at the Mathare North City Council Clinic in Nairobi Kenya, or referred from neighboring clinics, were recruited for study screening
    Pre-assignment Detail
    Arm/Group Title Valacyclovir Placebo
    Arm/Group Description 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum oral placebo twice daily from 34 weeks gestation to 1 year postpartum
    Period Title: Overall Study
    STARTED 74 74
    COMPLETED 67 69
    NOT COMPLETED 7 5

    Baseline Characteristics

    Arm/Group Title Valacyclovir Placebo Total
    Arm/Group Description 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum oral placebo twice daily from 34 weeks gestation to 1 year postpartum Total of all reporting groups
    Overall Participants 74 74 148
    Age (Count of Participants)
    <=18 years
    3
    4.1%
    4
    5.4%
    7
    4.7%
    Between 18 and 65 years
    71
    95.9%
    70
    94.6%
    141
    95.3%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    26.2
    (5.3)
    26.0
    (4.5)
    26.1
    (4.9)
    Sex: Female, Male (Count of Participants)
    Female
    74
    100%
    74
    100%
    148
    100%
    Male
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (participants) [Number]
    Kenya
    74
    100%
    74
    100%
    148
    100%

    Outcome Measures

    1. Primary Outcome
    Title Mean Change in HIV-1 Levels in Plasma Between 34 and 38 Weeks Gestation
    Description Calculated as log10 plasma viral load at 34 weeks gestation - log10 plasma viral load at 38 weeks gestation
    Time Frame 4 weeks

    Outcome Measure Data

    Analysis Population Description
    Women with paired plasma samples at 34 and 38 weeks gestation
    Arm/Group Title Valacyclovir Placebo
    Arm/Group Description 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum oral placebo twice daily from 34 weeks gestation to 1 year postpartum
    Measure Participants 51 49
    Mean (Standard Deviation) [log10 copies/mL]
    -0.53
    (.074)
    0.03
    (0.76)
    2. Secondary Outcome
    Title Vertical HIV-1 Transmission
    Description Mother-to-child HIV transmission
    Time Frame 1 year postpartum

    Outcome Measure Data

    Analysis Population Description
    Note the sample size is 73 for each group rather than 74 due to loss to follow-up.
    Arm/Group Title Valacyclovir Placebo
    Arm/Group Description 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum oral placebo twice daily from 34 weeks gestation to 1 year postpartum
    Measure Participants 73 73
    Number [Participants]
    6
    8.1%
    4
    5.4%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Valacyclovir Placebo
    Arm/Group Description 500 mg oral valacyclovir twice daily from 34 weeks gestation to 1 year postpartum oral placebo twice daily from 34 weeks gestation to 1 year postpartum
    All Cause Mortality
    Valacyclovir Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Valacyclovir Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/74 (1.4%) 2/74 (2.7%)
    Investigations
    Death 1/1 (100%) 1 2/2 (100%) 2
    Other (Not Including Serious) Adverse Events
    Valacyclovir Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/74 (0%) 0/74 (0%)

    Limitations/Caveats

    Unable to evaluate the effect of valacyclovir on mother-to-child HIV transmission (MTCT) or on change in HIV-1 RNA among women eligible for highly active antiretroviral therapy (HAART); lack power to detect association between treatment and MTCT.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Carey Farquhar
    Organization University of Washington
    Phone 206-543-4278
    Email cfarq@uw.edu
    Responsible Party:
    Carey Farquhar, Associate Professor, University of Washington
    ClinicalTrials.gov Identifier:
    NCT00530777
    Other Study ID Numbers:
    • 32462
    • 07-7306-A01
    • R03HD057773
    First Posted:
    Sep 17, 2007
    Last Update Posted:
    Dec 19, 2018
    Last Verified:
    Nov 1, 2018