BACKGROUND:Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria. METHODS:HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receivelopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach. RESULTS: Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms. CONCLUSIONS:Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART. CLINICAL TRIALS REGISTRATION: NCT00993031.
RCT Entities:
BACKGROUND: Human immunodeficiency virus (HIV)-infected pregnant women are at increased risk of malaria and its complications. In vitro and in vivo data suggest that the HIV protease inhibitors lopinavir/ritonavir may have potent antimalarial activity. We sought to evaluate whether lopinavir/ritonavir-based antiretroviral therapy (ART) reduced the risk of placental malaria. METHODS:HIV-infected, ART-naive pregnant women were enrolled between gestational weeks 12 and 28 and randomly assigned to receive lopinavir/ritonavir-based or efavirenz-based ART. Women received daily trimethoprim-sulfamethoxazole prophylaxis and insecticide-treated bed nets at enrollment and were followed up to 1 year after delivery. The primary outcome was placental malaria, defined by the detection of malaria parasites, using microscopy or polymerase chain reaction (PCR) analysis of placental blood specimens. Secondary outcomes included placental malaria, defined by histopathologic results; adverse birth outcomes; incidence of malaria; and prevalence of asymptomatic parasitemia. Analyses were done using an intention-to-treat approach. RESULTS: Of 389 subjects randomly assigned to a treatment group, 377 were followed through to delivery. There was no significant difference in the risk of placental malaria, as defined by thick smear or PCR findings, between the lopinavir/ritonavir-based and efavirenz-based ART arms (7.4% vs 9.8%; P = .45). Similarly, there were no differences in secondary outcomes between the 2 treatment arms. CONCLUSIONS:Lopinavir/ritonavir-based ART did not reduce the risk of placental or maternal malaria or improve birth outcomes, compared with efavirenz-based ART. CLINICAL TRIALS REGISTRATION: NCT00993031.
Authors: Meghna Desai; Feiko O ter Kuile; François Nosten; Rose McGready; Kwame Asamoa; Bernard Brabin; Robert D Newman Journal: Lancet Infect Dis Date: 2007-02 Impact factor: 25.071
Authors: Joel Tarning; Rose McGready; Niklas Lindegardh; Elizabeth A Ashley; Mupawjay Pimanpanarak; Benjamas Kamanikom; Anna Annerberg; Nicholas P J Day; Kasia Stepniewska; Pratap Singhasivanon; Nicholas J White; François Nosten Journal: Antimicrob Agents Chemother Date: 2009-06-29 Impact factor: 5.191
Authors: Paul Edward Okello; Wim Van Bortel; Anatol Maranda Byaruhanga; Anne Correwyn; Patricia Roelants; Ambrose Talisuna; Umberto D'Alessandro; Marc Coosemans Journal: Am J Trop Med Hyg Date: 2006-08 Impact factor: 2.345
Authors: Atupele Kapito-Tembo; Steven R Meshnick; Michaël Boele van Hensbroek; Kamija Phiri; Margaret Fitzgerald; Victor Mwapasa Journal: J Infect Dis Date: 2011-01-07 Impact factor: 5.226
Authors: Taylor G Sandison; Jaco Homsy; Emmanuel Arinaitwe; Humphrey Wanzira; Abel Kakuru; Victor Bigira; Julius Kalamya; Neil Vora; James Kublin; Moses R Kamya; Grant Dorsey; Jordan W Tappero Journal: BMJ Date: 2011-03-31
Authors: Patrick M Newman; Humphrey Wanzira; Gabriel Tumwine; Emmanuel Arinaitwe; Sarah Waldman; Jane Achan; Diane Havlir; Philip J Rosenthal; Grant Dorsey; Tamara D Clark; Deborah Cohan Journal: Malar J Date: 2009-11-14 Impact factor: 2.979
Authors: Chloe R McDonald; Andrea L Conroy; Joel L Gamble; Eszter Papp; Michael Hawkes; Peter Olwoch; Paul Natureeba; Moses Kamya; Michael Silverman; Deborah Cohan; Catherine A Koss; Grant Dorsey; Kevin C Kain; Lena Serghides Journal: Clin Infect Dis Date: 2018-01-18 Impact factor: 9.079
Authors: Abel Kakuru; Prasanna Jagannathan; Mary K Muhindo; Paul Natureeba; Patricia Awori; Miriam Nakalembe; Bishop Opira; Peter Olwoch; John Ategeka; Patience Nayebare; Tamara D Clark; Margaret E Feeney; Edwin D Charlebois; Gabrielle Rizzuto; Atis Muehlenbachs; Diane V Havlir; Moses R Kamya; Grant Dorsey Journal: N Engl J Med Date: 2016-03-10 Impact factor: 91.245
Authors: Paul Natureeba; Abel Kakuru; Mary Muhindo; Teddy Ochieng; John Ategeka; Catherine A Koss; Albert Plenty; Edwin D Charlebois; Tamara D Clark; Bridget Nzarubara; Miriam Nakalembe; Deborah Cohan; Gabrielle Rizzuto; Atis Muehlenbachs; Theodore Ruel; Prasanna Jagannathan; Diane V Havlir; Moses R Kamya; Grant Dorsey Journal: J Infect Dis Date: 2017-07-01 Impact factor: 5.226
Authors: Deborah Cohan; Paul Natureeba; Catherine A Koss; Albert Plenty; Flavia Luwedde; Julia Mwesigwa; Veronica Ades; Edwin D Charlebois; Monica Gandhi; Tamara D Clark; Bridget Nzarubara; Jane Achan; Theodore Ruel; Moses R Kamya; Diane V Havlir Journal: AIDS Date: 2015-01-14 Impact factor: 4.177
Authors: Catherine A Koss; Paul Natureeba; Dalsone Kwarisiima; Mike Ogena; Tamara D Clark; Peter Olwoch; Deborah Cohan; Jaffer Okiring; Edwin D Charlebois; Moses R Kamya; Diane V Havlir Journal: J Acquir Immune Defic Syndr Date: 2017-03-01 Impact factor: 3.731
Authors: Carina Marquez; Gabriel Chamie; Jane Achan; Anne F Luetkemeyer; Mary Kyohere; Jaffer Okiring; Grant Dorsey; Moses R Kamya; Edwin D Charlebois; Diane V Havlir Journal: Pediatr Infect Dis J Date: 2016-05 Impact factor: 2.129