title: Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.
abstract: BACKGROUND
  Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs).
  
  
  RESULTS
  A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis.
  
  
  CONCLUSIONS
  An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this particularly vulnerable group. MQ was associated with an increased risk of mother to child transmission of HIV, which warrants a better understanding of the pharmacological interactions between antimalarials and antiretroviral drugs.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Raquel
authors.initials: R
authors.lastname: González
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) Research and Public Health Collaboration, Kisumu, Kenya; Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, and Kisumu, Kenya.
authors.forename: Meghna
authors.initials: M
authors.lastname: Desai
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Eusebio
authors.initials: E
authors.lastname: Macete
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) Research and Public Health Collaboration, Kisumu, Kenya; Kenya Medical Research Institute (KEMRI)/Center for Global Health Research, Kisumu, Kenya.
authors.forename: Peter
authors.initials: P
authors.lastname: Ouma
authors.affiliation: Ifakara Health Institute (IHI), Dodoma, Tanzania.
authors.forename: Mwaka A
authors.initials: MA
authors.lastname: Kakolwa
authors.affiliation: Ifakara Health Institute (IHI), Dodoma, Tanzania.
authors.forename: Salim
authors.initials: S
authors.lastname: Abdulla
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: John J
authors.initials: JJ
authors.lastname: Aponte
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Helder
authors.initials: H
authors.lastname: Bulo
authors.affiliation: Ifakara Health Institute (IHI), Dodoma, Tanzania.
authors.forename: Abdunoor M
authors.initials: AM
authors.lastname: Kabanywanyi
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) Research and Public Health Collaboration, Kisumu, Kenya; Kenya Medical Research Institute (KEMRI)/Center for Global Health Research, Kisumu, Kenya.
authors.forename: Abraham
authors.initials: A
authors.lastname: Katana
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Sonia
authors.initials: S
authors.lastname: Maculuve
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mayor
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Arsenio
authors.initials: A
authors.lastname: Nhacolo
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) Research and Public Health Collaboration, Kisumu, Kenya; Kenya Medical Research Institute (KEMRI)/Center for Global Health Research, Kisumu, Kenya.
authors.forename: Kephas
authors.initials: K
authors.lastname: Otieno
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain.
authors.forename: Golbahar
authors.initials: G
authors.lastname: Pahlavan
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: María
authors.initials: M
authors.lastname: Rupérez
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Esperança
authors.initials: E
authors.lastname: Sevene
authors.affiliation: Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, and Kisumu, Kenya.
authors.forename: Laurence
authors.initials: L
authors.lastname: Slutsker
authors.affiliation: Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Anifa
authors.initials: A
authors.lastname: Vala
authors.affiliation: Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC) Research and Public Health Collaboration, Kisumu, Kenya; Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America, and Kisumu, Kenya.
authors.forename: John
authors.initials: J
authors.lastname: Williamsom
authors.affiliation: Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), ISGlobal, Barcelona Institute for Global Health, Barcelona, Spain; Manhiça Health Research Center (CISM), Manhiça, Mozambique.
authors.forename: Clara
authors.initials: C
authors.lastname: Menéndez
mesh_terms: D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D007630:Kenya / Q000453:epidemiology; D008288:Malaria / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D015767:Mefloquine / Q000008:administration & dosage*; D009073:Mozambique / Q000453:epidemiology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D015597:Pregnancy Complications, Parasitic / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control; D011256:Pregnancy Outcome; D013636:Tanzania / Q000453:epidemiology; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D000962:Antimalarials; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D015767:Mefloquine