Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

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...

Descripción completa

Detalles Bibliográficos
Autores principales: González, Raquel, Desai, Meghna, Macete, Eusebio, Ouma, Peter, Kakolwa, Mwaka A., Abdulla, Salim, Aponte, John J., Bulo, Helder, Kabanywanyi, Abdunoor M., Katana, Abraham, Maculuve, Sonia, Mayor, Alfredo, Nhacolo, Arsenio, Otieno, Kephas, Pahlavan, Golbahar, Rupérez, María, Sevene, Esperança, Slutsker, Laurence, Vala, Anifa, Williamsom, John, Menéndez, Clara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172537/
https://www.ncbi.nlm.nih.gov/pubmed/25247995
http://dx.doi.org/10.1371/journal.pmed.1001735
_version_ 1782336043945558016
author González, Raquel
Desai, Meghna
Macete, Eusebio
Ouma, Peter
Kakolwa, Mwaka A.
Abdulla, Salim
Aponte, John J.
Bulo, Helder
Kabanywanyi, Abdunoor M.
Katana, Abraham
Maculuve, Sonia
Mayor, Alfredo
Nhacolo, Arsenio
Otieno, Kephas
Pahlavan, Golbahar
Rupérez, María
Sevene, Esperança
Slutsker, Laurence
Vala, Anifa
Williamsom, John
Menéndez, Clara
author_facet González, Raquel
Desai, Meghna
Macete, Eusebio
Ouma, Peter
Kakolwa, Mwaka A.
Abdulla, Salim
Aponte, John J.
Bulo, Helder
Kabanywanyi, Abdunoor M.
Katana, Abraham
Maculuve, Sonia
Mayor, Alfredo
Nhacolo, Arsenio
Otieno, Kephas
Pahlavan, Golbahar
Rupérez, María
Sevene, Esperança
Slutsker, Laurence
Vala, Anifa
Williamsom, John
Menéndez, Clara
author_sort González, Raquel
collection PubMed
description 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). METHODS AND FINDINGS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary
format Online
Article
Text
id pubmed-4172537
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-41725372014-10-02 Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial González, Raquel Desai, Meghna Macete, Eusebio Ouma, Peter Kakolwa, Mwaka A. Abdulla, Salim Aponte, John J. Bulo, Helder Kabanywanyi, Abdunoor M. Katana, Abraham Maculuve, Sonia Mayor, Alfredo Nhacolo, Arsenio Otieno, Kephas Pahlavan, Golbahar Rupérez, María Sevene, Esperança Slutsker, Laurence Vala, Anifa Williamsom, John Menéndez, Clara PLoS Med Research Article 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). METHODS AND FINDINGS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary Public Library of Science 2014-09-23 /pmc/articles/PMC4172537/ /pubmed/25247995 http://dx.doi.org/10.1371/journal.pmed.1001735 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
González, Raquel
Desai, Meghna
Macete, Eusebio
Ouma, Peter
Kakolwa, Mwaka A.
Abdulla, Salim
Aponte, John J.
Bulo, Helder
Kabanywanyi, Abdunoor M.
Katana, Abraham
Maculuve, Sonia
Mayor, Alfredo
Nhacolo, Arsenio
Otieno, Kephas
Pahlavan, Golbahar
Rupérez, María
Sevene, Esperança
Slutsker, Laurence
Vala, Anifa
Williamsom, John
Menéndez, Clara
Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title_full Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title_fullStr Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title_full_unstemmed Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title_short Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial
title_sort intermittent preventive treatment of malaria in pregnancy with mefloquine in hiv-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4172537/
https://www.ncbi.nlm.nih.gov/pubmed/25247995
http://dx.doi.org/10.1371/journal.pmed.1001735
work_keys_str_mv AT gonzalezraquel intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT desaimeghna intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT maceteeusebio intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT oumapeter intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT kakolwamwakaa intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT abdullasalim intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT apontejohnj intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT bulohelder intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT kabanywanyiabdunoorm intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT katanaabraham intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT maculuvesonia intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT mayoralfredo intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT nhacoloarsenio intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT otienokephas intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT pahlavangolbahar intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT ruperezmaria intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT seveneesperanca intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT slutskerlaurence intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT valaanifa intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT williamsomjohn intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial
AT menendezclara intermittentpreventivetreatmentofmalariainpregnancywithmefloquineinhivinfectedwomenreceivingcotrimoxazoleprophylaxisamulticenterrandomizedplacebocontrolledtrial