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Clinical Trials

MainTitle

Interactions Between HIV and Malaria in African Children (TCC)

This study has been completed
Sponsor
University of California, San Francisco

Collaborator
Centers for Disease Control and Prevention
Makerere University
The AIDS Support Organization

Information provided by (Responsible Party)
University of California, San Francisco
ClinicalTrials.gov Identifier
NCT00527800

First received: September 10, 2007
Last updated: October 9, 2013
Last Verified: October 2013
History of Changes
Purpose

Purpose

This is a prospective cohort study where HIV-infected and uninfected children will be enrolled between 6 weeks and 9 months of age and followed to the age of 21 months. All HIV-infected children will be given trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis as of 6 weeks of age. HIV-uninfected children born to HIV-infected mothers will be given TMP/SMX prophylaxis for the duration of breastfeeding and then randomized to the continuation of TMP/SMX or discontinuation of TMP/SMX prophylaxis. HIV-uninfected children born to HIV-uninfected mothers will not be given TMP/SMX prophylaxis. Study participants will be followed for all of their health care needs in a designated study clinic. All mother-child pairs will receive a basic care package including insecticide-treated bednets (ITNs) at enrollment. All HIV-infected mothers and children will receive antiretroviral therapy if eligible according to standardized World Health Organization (WHO) criteria. Study participants 4 months of age or older and at least 5 kg will be randomized to treatment with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) at the time of their first diagnosis of uncomplicated malaria. Study participants will receive the same antimalarial treatment regimen for all future episodes of uncomplicated malaria. Study participants less than 4 months of age or less than 5 kg diagnosed with malaria and all episodes of complicated malaria will be treated with quinine in accordance with local guidelines.

The investigators will test the hypotheses that:

  1. TMP/SMX prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected children
  2. The use of TMP/SMX prophylaxis is associated with an increased risk of infection with malaria parasites containing antifolate resistance-conferring mutations.
  3. The use of antiretroviral (ARV) drugs is associated with a decreased incidence of malaria.
  4. The efficacy, safety, and tolerability of AL and DP for the treatment of uncomplicated malaria differ.

In 2008, we received approval and funding to extend the trial until 2012. We are now following all children through 5 years of age. First randomization to continue or discontinue TMP/SMX prophylaxis in our HIV-exposed population occurs 6-8 weeks after cessation of breastfeeding when HIV status can be confirmed as negative by DNA PCR. A second randomization occurs at 2 years of age in our HIV-exposed participants. At that point all HIV-exposed children who were originally randomized to continue TMP/SMX prophylaxis are again randomized to either immediately discontinue TMP/SMX prophylaxis or continue prophylaxis until age 4 years. All children will be off TMP/SMX between 4 and 5 years of age.
We have also added an additional hypothesis to test during the study extension:
  • Prolonged TMP/SMX prophylaxis will result in an increased incidence of malaria in children in the year immediately following cessation of prophylaxis compared to children who have not used prophylaxis for over a year and those who have never been on prophylaxis.

    Condition Intervention Phase
    Malaria
    HIV Infections

    Drug : Dihydroartemisinin-piperaquine
    Drug : Artemether-lumefantrine
    Drug : Trimethoprim-sulfamethoxazole
    Phase 3

    Study Type: Interventional
    Study Design: Allocation: Randomized
    Intervention Model: Factorial Assignment
    Masking: None (Open Label)
    Primary Purpose: Treatment
    Official Title: Interactions Between HIV and Malaria in African Children

    Further study details as provided by University of California, San Francisco:

    Primary Outcome Measures

    • Incidence of clinical episodes of malaria [ Time Frame: over entire course of follow-up ]
    • Risk of treatment failure at Day 28 defined as any early treatment failure or late clinical/parasitological failure adjusted and unadjusted by genotyping to distinguish recrudescence (treatment failure due to drug resistance) and new infections [ Time Frame: 28 days following each malaria treatment ]
    Secondary Outcome Measures:
    • Prevalence of mutations known to confer resistance to antifolate drugs in pretreatment samples from patients diagnosed with malaria [ Time Frame: each time episode of malaria is diagnosed ]
    • Risk of adverse events [ Time Frame: 28 days following each malaria treatment ]

    Enrollment: 351
    Study Start Date: August 2007
    Study Completion Date: March 2013
    Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

    Arms Assigned Interventions
    Experimental: 1
    Treatment for episodes of uncomplicated malaria
    Drug: Dihydroartemisinin-piperaquine

    Once daily for 3 days, given in fixed dose tablets (40 mg dihydroartemisinin + 320 mg piperaquine) according to weight-based guidelines

    Active Comparator: 2
    Treatment for uncomplicated malaria
    Drug: Artemether-lumefantrine

    Dosed twice daily for 3 days, given in fixed dose tablets (20 mg artemether + 120 mg lumefantrine) according to weight-based guidelines

    Experimental: A
    Prevention of malaria in HIV uninfected, exposed children
    Drug: Trimethoprim-sulfamethoxazole

    Once daily dosing according to weight based guidelines

    No Intervention: B
    Prevention of malaria in HIV uninfected, exposed children
    Eligibility

    Eligibility

    Ages Eligible for Study: 6 Weeks to 9 Months  
    Sexes Eligible for Study: All  
    Accepts Healthy Volunteers: Yes  

    Criteria

    Inclusion Criteria:

      1. Age 6 weeks to 9 months
      2. Documented HIV-1 status of mother and child
      3. Agreement to come to the study clinic for any febrile episode or other illness
      4. Agreement to avoid medications administered outside the study protocol
      5. Guardian age 18 years or older (no age limit for parents)
      6. Parent or guardian willing to provide informed consent
      7. Residence within a 30 km radius of the study clinic


    Exclusion Criteria:
      1. HIV-exposed infants who have already stopped receiving TMP/SMX as a result of having stopped breastfeeding and having been tested HIV-negative before screening
      2. Intention to move more than 30 km from the study clinic during the follow-up period
      3. History of allergy or sensitivity to AL or DP or TMP/SMX
      4. Active medical problem requiring in-patient evaluation at the time of screening

    contacts and locations

    Contacts and Locations

    Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00527800

    Locations

    Uganda
    Tororo District Hospital
    Tororo, Uganda

    Sponsors and Collaborators

    University of California, San Francisco
    Centers for Disease Control and Prevention
    Makerere University
    The AIDS Support Organization

    Investigators

    Principal Investigator: Grant Dorsey, MD, PhD University of California, San Francisco
    More Information

    More Information

    Additional Information:

    MU-UCSF Research Collaboration website

    Responsible Party: University of California, San Francisco  
    ClinicalTrials.gov Identifier: NCT00527800   History of Changes  
    Other Study ID Numbers: CDC- PEPFAR CoAg#U62P024421  
    Study First Received: September 10, 2007  
    Last Updated: October 9, 2013  

    Keywords provided by University of California, San Francisco:

    Malaria
    HIV
    Trimethoprim-sulfamethoxazole
    Artemether-lumefantrine
    Dihydroartemisinin-piperaquine
    Acute Infection

    Additional relevant MeSH terms:
    HIV Infections
    Malaria
    Lumefantrine
    Artemether
    Piperaquine
    Trimethoprim
    Artemether-lumefantrine combination
    Artemisinins
    Dihydroartemisinin
    Trimethoprim, Sulfamethoxazole Drug Combination
    Sulfamethoxazole

    ClinicalTrials.gov processed this data on October 23, 2017
    This information is provided by ClinicalTrials.gov.