<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03284645</url>
  </required_header>
  <id_info>
    <org_study_id>NHREC/01/01/2007-05/06/2017</org_study_id>
    <nct_id>NCT03284645</nct_id>
  </id_info>
  <brief_title>Viral and Antiretroviral Dynamics in HIV-1 Mother-to-Child Transmission Fluids</brief_title>
  <acronym>VADICT</acronym>
  <official_title>Investigating Influence of Pregnancy-induced Changes in Antiretroviral Pharmacokinetics, Together With Polymorphisms in Drug Disposition Genes, on Viral Decay Dynamics in HIV Positive Women Starting Therapy Late in Pregnancy and Postpartum</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Obafemi Awolowo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Federal Medical Centre, Makurdi</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Liverpool</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London School of Hygiene and Tropical Medicine</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Obafemi Awolowo University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      More than 150,000 babies became infected with HIV in 2015 alone. When HIV drugs are started&#xD;
      before or early in pregnancy, HIV positive women can give birth to HIV negative baby. This is&#xD;
      possible because HIV drugs can reduce the amount of the virus in the body to the extent that&#xD;
      they become undetectable by the time of delivery and during the breastfeeding period.&#xD;
      However, some women do not start taking these drugs on time because they become infected&#xD;
      during pregnancy or lactation. This leads to detectable virus at the time of delivery and&#xD;
      puts the baby at risk of becoming infected. Also, the amounts of HIV drugs in the body have&#xD;
      to be at certain levels for them to work effectively. But findings from some research have&#xD;
      recently showed that pregnancy increases the rate at which the body removes some HIV drugs&#xD;
      used to prevent the transfer of HIV from mother to child. While this may not cause any&#xD;
      problem in women with no detectable virus before pregnancy, it may affect the rate at which&#xD;
      the HIV virus is removed from the body in those starting treatment late and may put the baby&#xD;
      at risk. This project will investigate whether the changes in drug exposure caused by&#xD;
      pregnancy or other factors have any effect on the rate at which the HIV virus is removed from&#xD;
      the body. HIV positive pregnant women and those who recently delivered will be recruited from&#xD;
      different hospitals and follow up will be until breastfeeding ends. The investigators will&#xD;
      not be involved in treatment decisions and the primary care provider will be responsible for&#xD;
      prescribing antiretroviral regimen based on current guidelines. Samples will be collected to&#xD;
      measure levels of the virus and the drugs in three fluids that transfer the virus to the&#xD;
      baby: blood, genital fluid, and breastmilk. The HIV status of the babies will be monitored&#xD;
      until they stop breastfeeding.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 22, 2017</start_date>
  <completion_date type="Actual">September 17, 2020</completion_date>
  <primary_completion_date type="Actual">December 31, 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Polymorphisms in antiretrovirals disposition genes</measure>
    <time_frame>At study enrolment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Minimum plasma drug concentration (Cmin)</measure>
    <time_frame>At 2-3 months before delivery and at 10-12 weeks postpartum</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum plasma drug concentration (Cmax)</measure>
    <time_frame>At 2-3 months before delivery and at 10-12 weeks postpartum</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC)</measure>
    <time_frame>At 2-3 months before delivery and at 10-12 weeks postpartum</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clearance over systemic availability (Cl/F)</measure>
    <time_frame>At 2-3 months before delivery and at 10-12 weeks postpartum</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-1 viral load (RNA &amp; DNA) in plasma</measure>
    <time_frame>Through study completion (1-2 monthly)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-1 viral load (RNA &amp; DNA) in breastmilk</measure>
    <time_frame>From 6 weeks postpartum through study completion (1-2 monthly)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>HIV-1 viral load (RNA &amp; DNA) in CVF</measure>
    <time_frame>From week 28 to delivery (monthly)</time_frame>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">194</enrollment>
  <condition>Human Immunodeficiency Virus Infection</condition>
  <arm_group>
    <arm_group_label>ART Before or Early in Pregnancy</arm_group_label>
    <description>HIV positive pregnant women who started antiretroviral therapy (ART) before or early in pregnancy for prevention of mother-to-child transmission of HIV and for their own health.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ART Started Third Trimester</arm_group_label>
    <description>HIV positive pregnant women starting antiretroviral therapy (ART) during the third trimester of pregnancy for prevention of mother-to-child transmission of HIV and for their own health.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ART Started Postpartum</arm_group_label>
    <description>HIV positive women starting antiretroviral therapy (ART) after delivery for prevention of mother-to-child transmission of HIV and for their own health.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg</intervention_name>
    <description>Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.</description>
    <arm_group_label>ART Before or Early in Pregnancy</arm_group_label>
    <arm_group_label>ART Started Postpartum</arm_group_label>
    <arm_group_label>ART Started Third Trimester</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg</intervention_name>
    <description>Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.</description>
    <arm_group_label>ART Before or Early in Pregnancy</arm_group_label>
    <arm_group_label>ART Started Postpartum</arm_group_label>
    <arm_group_label>ART Started Third Trimester</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily</intervention_name>
    <description>Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken once daily.</description>
    <arm_group_label>ART Before or Early in Pregnancy</arm_group_label>
    <arm_group_label>ART Started Postpartum</arm_group_label>
    <arm_group_label>ART Started Third Trimester</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This is cohort study of HIV positive pregnant or recently postpartum women receiving WHO&#xD;
        recommended first-line ART regimen. Pregnant women and nursing mothers initiating ART &lt; 4&#xD;
        months before delivery (n = 60) and &lt; 6 weeks postpartum (n = 60), respectively, and a&#xD;
        comparison group of pregnant women who initiated ART ≥ 4 months before delivery (n = 120)&#xD;
        will be recruited from four hospitals providing PMTCT services in Nigeria.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥ 18 years old&#xD;
&#xD;
          -  Planned exclusive breastfeeding until 6 months of age&#xD;
&#xD;
          -  Able to understand study information and comply with follow-up schedule&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe maternal or infant illness&#xD;
&#xD;
          -  Planned exclusive formula feeding&#xD;
&#xD;
          -  Taking medication with known or uncertain interaction with study drugs&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Adeniyi Olagunju, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Obafemi Awolowo University, Nigeria</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Monica's Hospital</name>
      <address>
        <city>Adikpo</city>
        <state>Benue State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Thomas' Hospital</name>
      <address>
        <city>Ihugh</city>
        <state>Benue State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bishop Murray Medical Centre</name>
      <address>
        <city>Makurdi</city>
        <state>Benue State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Federal Medical Centre</name>
      <address>
        <city>Makurdi</city>
        <state>Benue State</state>
        <country>Nigeria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Nigeria</country>
  </location_countries>
  <link>
    <url>https://wellcomeopenresearch.org/articles/4-34/v1</url>
    <description>Wellcome Open Research</description>
  </link>
  <reference>
    <citation>Olagunju A, Anweh D, Okafor O et al. Viral and antiretroviral dynamics in HIV mother-to-child transmission fluids (VADICT) - Protocol and data analysis plan for a cohort study [version 1; referees: awaiting peer review]. Wellcome Open Res 2019, 4:34</citation>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>September 2, 2017</study_first_submitted>
  <study_first_submitted_qc>September 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 15, 2017</study_first_posted>
  <last_update_submitted>October 12, 2020</last_update_submitted>
  <last_update_submitted_qc>October 12, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acquired Immunodeficiency Syndrome</mesh_term>
    <mesh_term>HIV Infections</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tenofovir</mesh_term>
    <mesh_term>Lamivudine</mesh_term>
    <mesh_term>Zidovudine</mesh_term>
    <mesh_term>Efavirenz</mesh_term>
    <mesh_term>Abacavir</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03284645
org study id: NHREC/01/01/2007-05/06/2017
nct id: NCT03284645
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
More than 150,000 babies became infected with HIV in 2015 alone. When HIV drugs are started
      before or early in pregnancy, HIV positive women can give birth to HIV negative baby. This is
      possible because HIV drugs can reduce the amount of the virus in the body to the extent that
      they become undetectable by the time of delivery and during the breastfeeding period.
      However, some women do not start taking these drugs on time because they become infected
      during pregnancy or lactation. This leads to detectable virus at the time of delivery and
      puts the baby at risk of becoming infected. Also, the amounts of HIV drugs in the body have
      to be at certain levels for them to work effectively. But findings from some research have
      recently showed that pregnancy increases the rate at which the body removes some HIV drugs
      used to prevent the transfer of HIV from mother to child. While this may not cause any
      problem in women with no detectable virus before pregnancy, it may affect the rate at which
      the HIV virus is removed from the body in those starting treatment late and may put the baby
      at risk. This project will investigate whether the changes in drug exposure caused by
      pregnancy or other factors have any effect on the rate at which the HIV virus is removed from
      the body. HIV positive pregnant women and those who recently delivered will be recruited from
      different hospitals and follow up will be until breastfeeding ends. The investigators will
      not be involved in treatment decisions and the primary care provider will be responsible for
      prescribing antiretroviral regimen based on current guidelines. Samples will be collected to
      measure levels of the virus and the drugs in three fluids that transfer the virus to the
      baby: blood, genital fluid, and breastmilk. The HIV status of the babies will be monitored
      until they stop breastfeeding.
observational model: Cohort
time perspective: Prospective
measure: Polymorphisms in antiretrovirals disposition genes
time frame: At study enrolment
measure: Minimum plasma drug concentration (Cmin)
time frame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Maximum plasma drug concentration (Cmax)
time frame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Area under the concentration-time curve (AUC)
time frame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: Clearance over systemic availability (Cl/F)
time frame: At 2-3 months before delivery and at 10-12 weeks postpartum
measure: HIV-1 viral load (RNA & DNA) in plasma
time frame: Through study completion (1-2 monthly)
measure: HIV-1 viral load (RNA & DNA) in breastmilk
time frame: From 6 weeks postpartum through study completion (1-2 monthly)
measure: HIV-1 viral load (RNA & DNA) in CVF
time frame: From week 28 to delivery (monthly)
arm group label: ART Before or Early in Pregnancy
description: HIV positive pregnant women who started antiretroviral therapy (ART) before or early in pregnancy for prevention of mother-to-child transmission of HIV and for their own health.
arm group label: ART Started Third Trimester
description: HIV positive pregnant women starting antiretroviral therapy (ART) during the third trimester of pregnancy for prevention of mother-to-child transmission of HIV and for their own health.
arm group label: ART Started Postpartum
description: HIV positive women starting antiretroviral therapy (ART) after delivery for prevention of mother-to-child transmission of HIV and for their own health.
intervention type: Drug
intervention name: Tenofovir Disoproxil Fumarate (TDF) 300 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg
description: Fixed-dose combination of 300 mg TDF, 300 mg 3TC and 600 mg EFV taken once daily.
arm group label: ART Before or Early in Pregnancy
arm group label: ART Started Postpartum
arm group label: ART Started Third Trimester
intervention type: Drug
intervention name: Abacavir (ABC) 600 mg + Lamivudine (3TC) 300 mg + Efavirenz (EFV) 600 mg
description: Fixed-dose combination of 600 mg ABC, 300 mg 3TC and 600 mg EFV taken once daily.
arm group label: ART Before or Early in Pregnancy
arm group label: ART Started Postpartum
arm group label: ART Started Third Trimester
intervention type: Drug
intervention name: Zidovudine (AZT) 300 mg + Lamivudine (3TC) 150 mg twice daily + Efavirenz (EFV) 600 mg once daily
description: Fixed-dose combination of 300 mg AZT and 150 mg 3TC taken twice daily, plus 600 mg EFV taken once daily.
arm group label: ART Before or Early in Pregnancy
arm group label: ART Started Postpartum
arm group label: ART Started Third Trimester
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: Female
gender based: Yes
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Adeniyi Olagunju, PhD
role: Principal Investigator
affiliation: Obafemi Awolowo University, Nigeria
facility: 
facility: 
facility: 
facility: 
country: Nigeria
url: https://wellcomeopenresearch.org/articles/4-34/v1
description: Wellcome Open Research
citation: Olagunju A, Anweh D, Okafor O et al. Viral and antiretroviral dynamics in HIV mother-to-child transmission fluids (VADICT) - Protocol and data analysis plan for a cohort study [version 1; referees: awaiting peer review]. Wellcome Open Res 2019, 4:34
responsible party type: Sponsor
mesh term: Acquired Immunodeficiency Syndrome
mesh term: HIV Infections
mesh term: Tenofovir
mesh term: Lamivudine
mesh term: Zidovudine
mesh term: Efavirenz
mesh term: Abacavir
sharing ipd: No