NCT00978068: PROMOTE-PEDS

A Randomized Open Label Trial of HIV Protease Inhibitors for the Prevention of Malaria in HIV-Infected Children

Completed Phase 3 Results posted Last updated 5 December 2018

What this trial tests

Phase 3 trial testing Lopinavir/Ritonavir (LPV/r) in Malaria in 176 participants. Completed in 1 January 2013.

Timeline

1 September 2009

Primary endpoint
1 January 2013

1 January 2013

Quick facts

Lead sponsor	University of California, San Francisco
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	176
Start date	1 September 2009
Primary completion	1 January 2013
Estimated completion	1 January 2013
Sites	1 location across Uganda

Drugs / interventions tested

• Lopinavir/Ritonavir (LPV/r) — full drug profile →
• Nevirapine (NVP) — full drug profile →
• Efavirenz (EFV) — full drug profile →
• 2 nucleoside reverse transcriptase inhibitor (NRTI) — full drug profile →

Conditions studied

• Malaria — all drugs for Malaria →
• HIV Infections — all drugs for HIV Infections →

Sponsor

University of California, San Francisco

Who can join

Adults 2 Months to 10, any sex, with Malaria or HIV Infections. Healthy volunteers can join.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Incidence-density of Malaria Defined as the Number of Incident Episodes of Malaria Per Time at Risk.
  Time frame: Time from randomization to at least 24 months of follow up or until end of the study

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Antiretroviral agents and prevention of malaria in HIV-infected Ugandan children.
   Achan J, Kakuru A, Ikilezi G, Ruel T, et al · · 2012 · cited 85× · PMID 23190222 · DOI 10.1056/nejmoa1200501
2. Impact of antimalarial treatment and chemoprevention on the drug sensitivity of malaria parasites isolated from ugandan children.
   Tumwebaze P, Conrad MD, Walakira A, LeClair N, et al · · 2015 · cited 62× · PMID 25753626 · DOI 10.1128/aac.05141-14
3. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.
   Bartelink IH, Savic RM, Dorsey G, Ruel T, et al · · 2015 · cited 26× · PMID 25742090 · DOI 10.1097/inf.0000000000000603
4. Virologic and immunologic outcomes of HIV-infected Ugandan children randomized to lopinavir/ritonavir or nonnucleoside reverse transcriptase inhibitor therapy.
   Ruel TD, Kakuru A, Ikilezi G, Mwangwa F, et al · · 2014 · cited 21× · PMID 24326597 · DOI 10.1097/qai.0000000000000071
5. Artemisinin-based combination therapies are efficacious and safe for treatment of uncomplicated malaria in HIV-infected Ugandan children.
   Kakuru A, Achan J, Muhindo MK, Ikilezi G, et al · · 2014 · cited 20× · PMID 24759826 · DOI 10.1093/cid/ciu286
6. How has mass drug administration with dihydroartemisinin-piperaquine impacted molecular markers of drug resistance? A systematic review.
   Moss S, Mańko E, Krishna S, Campino S, et al · · 2022 · cited 12× · PMID 35690758 · DOI 10.1186/s12936-022-04181-y
7. Growth Recovery Among HIV-infected Children Randomized to Lopinavir/Ritonavir or NNRTI-based Antiretroviral Therapy.
   Achan J, Kakuru A, Ikilezi G, Mwangwa F, et al · · 2016 · cited 11× · PMID 27580060 · DOI 10.1097/inf.0000000000001318
8. Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy.
   Bangirana P, Ruel TD, Boivin MJ, Pillai SK, et al · · 2017 · cited 8× · PMID 29052340 · DOI 10.1002/jia2.25015