Malaria in HIV-Infected Children Receiving HIV Protease-Inhibitor- Compared with Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy, IMPAACT P1068s, Substudy to P1060

PLoS One. 2016 Dec 9;11(12):e0165140. doi: 10.1371/journal.pone.0165140. eCollection 2016.


Background: HIV and malaria geographically overlap. HIV protease inhibitors kill malaria parasites in vitro and in vivo, but further evaluation in clinical studies is needed.

Methods: Thirty-one children from Malawi aged 4-62 months were followed every 3 months and at intercurrent illness visits for ≤47 months (September 2009-December 2011). We compared malaria parasite carriage by blood smear microscopy (BS) and confirmed clinical malaria incidence (CCM, or positive BS with malaria symptoms) in children initiated on HIV antiretroviral therapy (ART) with zidovudine, lamivudine, and either nevirapine (NVP), a non-nucleoside reverse transcriptase inhibitor, or lopinavir-ritonavir (LPV-rtv), a protease inhibitor.

Results: We found an association between increased time to recurrent positive BS, but not CCM, when anti-malarial treatment and LPV-rtv based ART were used concurrently and when accounting for a LPV-rtv and antimalarial treatment interaction (adjusted HR 0.39; 95% CI (0.17,0.89); p = 0.03).

Conclusions: LPV-rtv in combination with malaria treatment was associated with lower risk of recurrent positive BS, but not CCM, in HIV-infected children. Larger, randomized studies are needed to confirm these findings which may permit ART optimization for malaria-endemic settings.

Trial registration: NCT00719602.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Antimalarials / therapeutic use*
  • CD4 Lymphocyte Count
  • Child
  • Child, Preschool
  • Coinfection
  • Drug Therapy, Combination
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV Protease Inhibitors / therapeutic use*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • HIV-1 / growth & development
  • Humans
  • Infant
  • Lamivudine / therapeutic use
  • Lopinavir / therapeutic use
  • Malaria, Falciparum / drug therapy*
  • Malaria, Falciparum / immunology
  • Malaria, Falciparum / parasitology
  • Malawi
  • Male
  • Nevirapine / therapeutic use
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / growth & development
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Ritonavir / therapeutic use
  • Viral Load / drug effects
  • Zidovudine / therapeutic use


  • Antimalarials
  • HIV Protease Inhibitors
  • Reverse Transcriptase Inhibitors
  • Lopinavir
  • Lamivudine
  • Zidovudine
  • Nevirapine
  • Ritonavir

Associated data