HIV Protease Inhibitors for the Prevention of Malaria in Ugandan Children
PROMOTE-PEDS
A Randomized Open Label Trial of HIV Protease Inhibitors for the Prevention of Malaria in HIV-Infected Children
6 other identifiers
interventional
176
1 country
1
Brief Summary
HIV and malaria are major causes of morbidity and mortality in Sub-Saharan Africa and children bear the greatest brunt of both diseases. No single existing intervention is likely to control malaria in Africa. Rather, improvements in malaria prevention are likely to come from strategies that employ multiple proven interventions targeting different populations. HIV-infected children represent one of the most vulnerable subpopulations in these countries. It is possible that the use of protease inhibitor (PI) - based antiretroviral therapy (ART) in HIV-infected children living in areas of high malaria transmission could prevent malaria in this vulnerable population. An effective remedy that offers the possibility to further reduce malaria risk, such as PIs, is highly desirable. This study will determine whether a PI based ART regimen will reduce malaria among children living in a malaria endemic area of Uganda and receiving insecticide-treated bed nets (ITN) and TS. This study will compare two different ART regimens. Children enrolled in the study will start or continue to receive either standard Ugandan first line treatment ART regimen (NNRTI+2 NRTIs) or an ART regimen containing the HIV protease inhibitor (lopinavir/ritonavir +2 NRTIs) and followed for a period of 24 months.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Sep 2009
Typical duration for phase_3
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
September 1, 2009
CompletedFirst Submitted
Initial submission to the registry
September 14, 2009
CompletedFirst Posted
Study publicly available on registry
September 16, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
January 1, 2013
CompletedResults Posted
Study results publicly available
December 28, 2018
CompletedDecember 28, 2018
December 1, 2018
3.3 years
September 14, 2009
November 18, 2015
December 5, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Incidence-density of Malaria Defined as the Number of Incident Episodes of Malaria Per Time at Risk.
Time from randomization to at least 24 months of follow up or until end of the study
Secondary Outcomes (5)
Percentage of Uncomplicated Malaria Episodes With Accompanying Adverse Events That Occurred in the 28 Days Following Antimalarial Therapy
28 days after antimalarial therapy
Incidence-density of Malaria Defined as the Number of Incident Episodes of Complicated Malaria Per Time at Risk.
Time from randomization to at least 24 months of follow up or until end of the study
Estimates of the 6-month Risk of a First Episode of Malaria
Enrollment to 6 months follow up
28-day Risk of Recurrent Parasitemia
28 days after antimalarial therapy
63-day Risk of Recurrent Malaria
28 days after antimalarial therapy
Study Arms (2)
Lopinavir/ritonavir (LPV/r) +2 NRTI
ACTIVE COMPARATORLopinavir/ritonavir (LPV/r) +2 nucleoside reverse transcriptase inhibitor (NRTI)
Nevirapine (NVP) or Efavirenz (EFV) +2 NRTI
ACTIVE COMPARATORNevirapine (NVP) or Efavirenz (EFV) +2 nucleoside reverse transcriptase inhibitor (NRTI)
Interventions
NVP will be used for children \< 3 years of age
The same NRTI choice strategy will be used for both arms. Lamivudine will be used with all children. The second NRTI will be zidovudine unless the participant has a hemoglobin \< 8 gm/dL, in which case it will be Abacavir. Stavudine will be used in the event that a participant is unable to take Abacavir for safety or other reasons.
Eligibility Criteria
You may qualify if:
- Age 2 months to \< 11 years
- Confirmed HIV diagnosis. i. Children \> 18 months: Documentation of HIV status must come from two assays. Assays include DNA PCR, HIV RNA, Western blot, or rapid HIV antibody test ii. Children \< 18 months: Documentation will be DNA PCR confirmation only along with documentation of testing from the referral entity
- ART-naïve patients eligible for ART initiation per WHO/Uganda guidelines (see Table 1) or Patients receiving first line ART regimen with NNRTI +2 NRTI with at least one HIV RNA \<400 copies/ml within the past 6 months
- Agreement to come to the study clinic for any febrile episode or other illness
- Agreement to avoid medications administered outside study protocol
- Provision of informed consent by parent/guardian and agreement to have child's care at the clinical site
- Lives within 50 km of study site
You may not qualify if:
- ART-naïve children: children or their mothers that have received any dose of Nevirapine in the past 24 months
- Active medical problem requiring in-patient evaluation at the time of screening or enrollment
- History of cardiac conduction disorder or known significant cardiac structural defect
- Children receiving any disallowed medications (see section 4.3)
- Moderate, Severe or Life-threatening (Grade 2, 3, or 4) AST or ALT found within 4 weeks prior to enrollment:
- AST: \>113U/L (\>2.5xULN)
- ALT: \>113U/L (\>2.5xULN)
- Life-threatening (Grade 4) screening laboratory value found within 4 weeks prior to enrollment for the following:
- Absolute neutrophil count: \<500 mm3
- Hemoglobin: \<6.5 g/dL
- Creatinine: \>3.5xULN
- Platelets: \<25,000/mm3
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
IDRC - Tororo Research Clinic
Tororo, Uganda
Related Publications (8)
Achan J, Kakuru A, Ikilezi G, Ruel T, Clark TD, Nsanzabana C, Charlebois E, Aweeka F, Dorsey G, Rosenthal PJ, Havlir D, Kamya MR. Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children. N Engl J Med. 2012 Nov 29;367(22):2110-8. doi: 10.1056/NEJMoa1200501.
PMID: 23190222RESULTIkilezi G, Achan J, Kakuru A, Ruel T, Charlebois E, Clark TD, Rosenthal PJ, Havlir D, Kamya MR, Dorsey G. Prevalence of asymptomatic parasitemia and gametocytemia among HIV-infected Ugandan children randomized to receive different antiretroviral therapies. Am J Trop Med Hyg. 2013 Apr;88(4):744-6. doi: 10.4269/ajtmh.12-0658. Epub 2013 Jan 28.
PMID: 23358639RESULTNsanzabana C, Rosenthal PJ. In vitro activity of antiretroviral drugs against Plasmodium falciparum. Antimicrob Agents Chemother. 2011 Nov;55(11):5073-7. doi: 10.1128/AAC.05130-11. Epub 2011 Aug 29.
PMID: 21876053RESULTRuel TD, Kakuru A, Ikilezi G, Mwangwa F, Dorsey G, Rosenthal PJ, Charlebois E, Havlir D, Kamya M, Achan J. Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy. J Acquir Immune Defic Syndr. 2014 Apr 15;65(5):535-41. doi: 10.1097/QAI.0000000000000071.
PMID: 24326597RESULTKakuru A, Achan J, Muhindo MK, Ikilezi G, Arinaitwe E, Mwangwa F, Ruel T, Clark TD, Charlebois E, Rosenthal PJ, Havlir D, Kamya MR, Tappero JW, Dorsey G. Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children. Clin Infect Dis. 2014 Aug 1;59(3):446-53. doi: 10.1093/cid/ciu286. Epub 2014 Apr 23.
PMID: 24759826RESULTBartelink IH, Savic RM, Dorsey G, Ruel T, Gingrich D, Scherpbier HJ, Capparelli E, Jullien V, Young SL, Achan J, Plenty A, Charlebois E, Kamya M, Havlir D, Aweeka F. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda. Pediatr Infect Dis J. 2015 Mar;34(3):e63-70. doi: 10.1097/INF.0000000000000603.
PMID: 25742090RESULTAchan J, Kakuru A, Ikilezi G, Mwangwa F, Plenty A, Charlebois E, Young S, Havlir D, Kamya M, Ruel T. Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy. Pediatr Infect Dis J. 2016 Dec;35(12):1329-1332. doi: 10.1097/INF.0000000000001318.
PMID: 27580060RESULTBangirana P, Ruel TD, Boivin MJ, Pillai SK, Giron LB, Sikorskii A, Banik A, Achan J. Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy. J Int AIDS Soc. 2017 Oct;20(2):e25015. doi: 10.1002/jia2.25015.
PMID: 29052340DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study has limited statistical power for the comparison of uncommon events and limited evaluation of potential cardiotoxic effects, hence future studies of the safety of coadministration of lopinavir-ritonavir and lumefantrine are warranted.
Results Point of Contact
- Title
- Tamara Clark
- Organization
- University of California, San Francisco
Study Officials
- STUDY DIRECTOR
Diane V Havlir, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Moses R Kamya MBChB, MMed, MPH
Makerere University
- PRINCIPAL INVESTIGATOR
Grant Dorsey, MD, PhD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Ted Ruel, MD
University of California, San Francisco
- PRINCIPAL INVESTIGATOR
Jane Achan, MBChB, MPed
Makerere University
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 14, 2009
First Posted
September 16, 2009
Study Start
September 1, 2009
Primary Completion
January 1, 2013
Study Completion
January 1, 2013
Last Updated
December 28, 2018
Results First Posted
December 28, 2018
Record last verified: 2018-12