Interactions Between HIV and Malaria in African Children (TCC)

This study has been completed.
Sponsor:
Collaborators:
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
  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:

  5. 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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Interactions Between HIV and Malaria in African Children

Resource links provided by NLM:


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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • Risk of adverse events [ Time Frame: 28 days following each malaria treatment ] [ Designated as safety issue: Yes ]

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

Ages Eligible for Study:   6 Weeks to 9 Months
Genders Eligible for Study:   Both
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
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
Makerere University
The AIDS Support Organization
Investigators
Principal Investigator: Grant Dorsey, MD, PhD University of California, San Francisco
  More Information

Additional Information:
Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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
Health Authority: Uganda: National Council for Science and Technology
Uganda: Research Ethics Committee
United States: Institutional Review Board

Keywords provided by University of California, San Francisco:
Malaria
HIV
Trimethoprim-sulfamethoxazole
Artemether-lumefantrine
Dihydroartemisinin-piperaquine
Acute Infection

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Malaria
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Protozoan Infections
Parasitic Diseases
Artemether
Dihydroartemisinin
Piperaquine
Lumefantrine
Artemether-lumefantrine combination
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Artemisinins
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Infective Agents, Urinary
Renal Agents
Antimalarials
Antiprotozoal Agents

ClinicalTrials.gov processed this record on July 31, 2014