Interactions Between HIV and Malaria in African Children (TCC)
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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:
- TMP/SMX prophylaxis is highly effective in preventing malaria in both HIV-infected and HIV-uninfected children
- The use of TMP/SMX prophylaxis is associated with an increased risk of infection with malaria parasites containing antifolate resistance-conferring mutations.
- The use of antiretroviral (ARV) drugs is associated with a decreased incidence of malaria.
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 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 |
- 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 ]
- 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 |
Estimated Study Completion Date: | April 2012 |
Estimated Primary Completion Date: | April 2012 (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
|
Ages Eligible for Study: | 6 Weeks to 9 Months |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
- Age 6 weeks to 9 months
- Documented HIV-1 status of mother and child
- Agreement to come to the study clinic for any febrile episode or other illness
- Agreement to avoid medications administered outside the study protocol
- Guardian age 18 years or older (no age limit for parents)
- Parent or guardian willing to provide informed consent
- Residence within a 30 km radius of the study clinic
Exclusion Criteria:
- 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
- Intention to move more than 30 km from the study clinic during the follow-up period
- History of allergy or sensitivity to AL or DP or TMP/SMX
- Active medical problem requiring in-patient evaluation at the time of screening
Uganda | |
Tororo District Hospital | |
Tororo, Uganda |
Principal Investigator: | Grant Dorsey, MD, PhD | University of California, San Francisco |
Additional Information:
No publications provided by University of California, San Francisco
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Grant Dorsey, M.D, Ph.D., Associate Professor, Infectious Disease, 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: | April 16, 2012 |
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 |
Dihydroquinghaosu 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 March 10, 2013