Interactions Between HIV and Malaria in African Children
NCT ID: NCT00527800
Last Updated: 2013-10-11
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE3
351 participants
INTERVENTIONAL
2007-08-31
2013-03-31
Brief Summary
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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.
Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
FACTORIAL
TREATMENT
NONE
Study Groups
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1
Treatment for episodes of uncomplicated malaria
Dihydroartemisinin-piperaquine
Once daily for 3 days, given in fixed dose tablets (40 mg dihydroartemisinin + 320 mg piperaquine) according to weight-based guidelines
2
Treatment for uncomplicated malaria
Artemether-lumefantrine
Dosed twice daily for 3 days, given in fixed dose tablets (20 mg artemether + 120 mg lumefantrine) according to weight-based guidelines
A
Prevention of malaria in HIV uninfected, exposed children
Trimethoprim-sulfamethoxazole
Once daily dosing according to weight based guidelines
B
Prevention of malaria in HIV uninfected, exposed children
No interventions assigned to this group
Interventions
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Dihydroartemisinin-piperaquine
Once daily for 3 days, given in fixed dose tablets (40 mg dihydroartemisinin + 320 mg piperaquine) according to weight-based guidelines
Artemether-lumefantrine
Dosed twice daily for 3 days, given in fixed dose tablets (20 mg artemether + 120 mg lumefantrine) according to weight-based guidelines
Trimethoprim-sulfamethoxazole
Once daily dosing according to weight based guidelines
Eligibility Criteria
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Inclusion Criteria
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
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
6 Weeks
9 Months
ALL
Yes
Sponsors
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Centers for Disease Control and Prevention
FED
Makerere University
OTHER
The AIDS Support Organization
OTHER
University of California, San Francisco
OTHER
Responsible Party
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Principal Investigators
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Grant Dorsey, MD, PhD
Role: PRINCIPAL_INVESTIGATOR
University of California, San Francisco
Locations
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Tororo District Hospital
Tororo, , Uganda
Countries
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References
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Creek DJ, Bigira V, McCormack S, Arinaitwe E, Wanzira H, Kakuru A, Tappero JW, Sandison TG, Lindegardh N, Nosten F, Aweeka FT, Parikh S. Pharmacokinetic predictors for recurrent malaria after dihydroartemisinin-piperaquine treatment of uncomplicated malaria in Ugandan infants. J Infect Dis. 2013 Jun 1;207(11):1646-54. doi: 10.1093/infdis/jit078. Epub 2013 Feb 27.
Kakuru A, Jagannathan P, Arinaitwe E, Wanzira H, Muhindo M, Bigira V, Osilo E, Homsy J, Kamya MR, Tappero JW, Dorsey G. The effects of ACT treatment and TS prophylaxis on Plasmodium falciparum gametocytemia in a cohort of young Ugandan children. Am J Trop Med Hyg. 2013 Apr;88(4):736-43. doi: 10.4269/ajtmh.12-0654. Epub 2013 Feb 4.
Jagannathan P, Muhindo MK, Kakuru A, Arinaitwe E, Greenhouse B, Tappero J, Rosenthal PJ, Kaharuza F, Kamya MR, Dorsey G. Increasing incidence of malaria in children despite insecticide-treated bed nets and prompt anti-malarial therapy in Tororo, Uganda. Malar J. 2012 Dec 28;11:435. doi: 10.1186/1475-2875-11-435.
Arinaitwe E, Gasasira A, Verret W, Homsy J, Wanzira H, Kakuru A, Sandison TG, Young S, Tappero JW, Kamya MR, Dorsey G. The association between malnutrition and the incidence of malaria among young HIV-infected and -uninfected Ugandan children: a prospective study. Malar J. 2012 Mar 27;11:90. doi: 10.1186/1475-2875-11-90.
Sandison TG, Homsy J, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, Kalamya J, Vora N, Kublin J, Kamya MR, Dorsey G, Tappero JW. Protective efficacy of co-trimoxazole prophylaxis against malaria in HIV exposed children in rural Uganda: a randomised clinical trial. BMJ. 2011 Mar 31;342:d1617. doi: 10.1136/bmj.d1617.
Verret WJ, Arinaitwe E, Wanzira H, Bigira V, Kakuru A, Kamya M, Tappero JW, Sandison T, Dorsey G. Effect of nutritional status on response to treatment with artemisinin-based combination therapy in young Ugandan children with malaria. Antimicrob Agents Chemother. 2011 Jun;55(6):2629-35. doi: 10.1128/AAC.01727-10. Epub 2011 Mar 7.
Creek D, Bigira V, Arinaitwe E, Wanzira H, Kakuru A, Tappero J, Kamya MR, Dorsey G, Sandison TG. Increased risk of early vomiting among infants and young children treated with dihydroartemisinin-piperaquine compared with artemether-lumefantrine for uncomplicated malaria. Am J Trop Med Hyg. 2010 Oct;83(4):873-5. doi: 10.4269/ajtmh.2010.10-0158.
Vora N, Homsy J, Kakuru A, Arinaitwe E, Wanzira H, Sandison TG, Bigira V, Kamya MR, Tappero JW, Dorsey G. Breastfeeding and the risk of malaria in children born to HIV-infected and uninfected mothers in rural Uganda. J Acquir Immune Defic Syndr. 2010 Oct;55(2):253-61. doi: 10.1097/QAI.0b013e3181eb4fd7.
Katrak S, Gasasira A, Arinaitwe E, Kakuru A, Wanzira H, Bigira V, Sandison TG, Homsy J, Tappero JW, Kamya MR, Dorsey G. Safety and tolerability of artemether-lumefantrine versus dihydroartemisinin-piperaquine for malaria in young HIV-infected and uninfected children. Malar J. 2009 Nov 30;8:272. doi: 10.1186/1475-2875-8-272.
Arinaitwe E, Sandison TG, Wanzira H, Kakuru A, Homsy J, Kalamya J, Kamya MR, Vora N, Greenhouse B, Rosenthal PJ, Tappero J, Dorsey G. Artemether-lumefantrine versus dihydroartemisinin-piperaquine for falciparum malaria: a longitudinal, randomized trial in young Ugandan children. Clin Infect Dis. 2009 Dec 1;49(11):1629-37. doi: 10.1086/647946.
Homsy J, Dorsey G, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, Muhindo M, Kamya MR, Sandison TG, Tappero JW. Protective efficacy of prolonged co-trimoxazole prophylaxis in HIV-exposed children up to age 4 years for the prevention of malaria in Uganda: a randomised controlled open-label trial. Lancet Glob Health. 2014 Dec;2(12):e727-36. doi: 10.1016/S2214-109X(14)70329-8.
Wanzira H, Kakuru A, Arinaitwe E, Bigira V, Muhindo MK, Conrad M, Rosenthal PJ, Kamya MR, Tappero JW, Dorsey G. Longitudinal outcomes in a cohort of Ugandan children randomized to artemether-lumefantrine versus dihydroartemisinin-piperaquine for the treatment of malaria. Clin Infect Dis. 2014 Aug 15;59(4):509-16. doi: 10.1093/cid/ciu353. Epub 2014 May 13.
Conrad MD, LeClair N, Arinaitwe E, Wanzira H, Kakuru A, Bigira V, Muhindo M, Kamya MR, Tappero JW, Greenhouse B, Dorsey G, Rosenthal PJ. Comparative impacts over 5 years of artemisinin-based combination therapies on Plasmodium falciparum polymorphisms that modulate drug sensitivity in Ugandan children. J Infect Dis. 2014 Aug 1;210(3):344-53. doi: 10.1093/infdis/jiu141. Epub 2014 Mar 8.
Muhindo MK, Kakuru A, Jagannathan P, Talisuna A, Osilo E, Orukan F, Arinaitwe E, Tappero JW, Kaharuza F, Kamya MR, Dorsey G. Early parasite clearance following artemisinin-based combination therapy among Ugandan children with uncomplicated Plasmodium falciparum malaria. Malar J. 2014 Jan 28;13:32. doi: 10.1186/1475-2875-13-32.
Related Links
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MU-UCSF Research Collaboration website
Other Identifiers
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CDC- PEPFAR CoAg#U62P024421
Identifier Type: -
Identifier Source: org_study_id