| dc.description.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).
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. | en_US |
