Journal Article

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

Ouma, Peter, Abdulla, Salim, Otieno, Kephas, Nhacolo, Arsenio, Sevene, Esperança, Macete, Eusebio, Vala, Anifa, Aponte, John J., Slutsker, Laurence, Rupérez, María, Kabanywanyi, Abdunoor M., Mayor, Alfredo, Bulo, Helder, Williamsom, John, Menéndez, Clara, González, Raquel, Maculuve, Sonia, Pahlavan, Golbahar, Desai, Meghna, Kakolwa, Mwaka A., Katana, Abraham

2014

Overview

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). 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. 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. ClinicalTrials.gov NCT 00811421; Pan African Clinical Trials Registry PACTR 2010020001813440 Please see later in the article for the Editors' Summary.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Analysis / Antimalarials / Antimalarials - administration & dosage / Biology and Life Sciences / Care and treatment / Double-Blind Method / Female / Follow-Up Studies / Health aspects / HIV / HIV infection / HIV Infections - diagnosis / HIV Infections - drug therapy / HIV Infections - epidemiology / Human immunodeficiency virus / Humans / Infectious Disease Transmission, Vertical - prevention & control / Kenya - epidemiology / Malaria / Malaria - diagnosis / Malaria - epidemiology / Malaria - prevention & control / Medical research / Medicine and health sciences / Mefloquine - administration & dosage / Mozambique - epidemiology / Pregnancy / Pregnancy Complications, Infectious - diagnosis / Pregnancy Complications, Infectious - epidemiology / Pregnancy Complications, Infectious - prevention & control / Pregnancy Complications, Parasitic - diagnosis / Pregnancy Complications, Parasitic - epidemiology / Pregnancy Complications, Parasitic - prevention & control / Pregnancy Outcome / Pregnant women / Tanzania - epidemiology / Treatment Outcome / Trimethoprim, Sulfamethoxazole Drug Combination - administration & dosage / Womens health / Young Adult