therapy (ART) based on the protease inhibitor lopinavir/ritonavir (Kaletra) does not
reduce the risk of malaria among pregnant women living with HIV, research
published in the online edition of the Journal
of Infectious Diseases shows.
Previous research had suggested that the
protease inhibitor might have a potent anti-malaria activity. However, the
present study showed that malaria risk and malaria-associated adverse birth
outcomes were similar for women treated with the protease inhibitor and those
taking the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva or Stocrin).
“In this study,
pregnant women were randomised to lopinavir/ritonavir vs efavirenz-based ART to
test the hypothesis that a protease inhibitor based ART regimen would be
associated with a lower risk of malaria,” explain the authors. “We found there
was no difference between the two ART regimens in the risk of placental
malaria, the incidence of malaria, the prevalence of asymptomatic parasitemia,
and the risk of adverse birth outcomes.”
pregnancy is associated with adverse birth outcomes such as spontaneous
abortion, premature delivery and low birth weight. The risk of malaria and
adverse outcomes is especially severe for pregnant women living with HIV.
Strategies for the
prevention of malaria in pregnant women include the use of insecticide-treated
bednets and, for women living with HIV, daily prophylaxis with
trimethoprim-sulfamethoxazole (TNP-SMX). However, other prevention strategies
are urgently required.
antiretroviral therapy is recommended for all pregnant women living with HIV, and
there is some evidence this treatment can reduce the risk of malaria.
Laboratory studies have shown that protease inhibitors are effective against
the malaria parasite. Moreover, a study involving Ugandan school children
showed that treatment with an ART regimen based on lopinavir/ritonavir was
associated with a 41% reduction in malaria risk compared to therapy based on an
findings, a team of investigators wanted to see if HIV therapy based on
lopinavir/ritonavir reduced the risk of malaria during pregnancy compared to
NNRTI-based treatment, the current standard of care. They therefore designed a
randomised study involving treatment-naive women living with HIV who initiated
antiretroviral therapy between weeks 12 and 28 of pregnancy. The women were
randomised to take therapy based on lopinavir/ritonavir or efavirenz. The
investigators compared the risk of placental malaria up to one year after
delivery between the two regimens. Other outcomes included placental malaria
diagnosed using histology, adverse birth outcomes, incidence of malaria and the
prevalence of asymptomatic malaria parasites.
The study was
conducted in the Ugandan region of Tororo where malaria is endemic. A total of 389
women were recruited between 2009 and 2013 and 377 initiated therapy.
Eight weeks after
starting HIV therapy, approximately 88% of women had an undetectable viral
load. Adherence to HIV therapy was high (97-99%) as was adherence to malaria
Regardless of the
testing method used, the prevalence of placental malaria did not differ between
lopinavir/ritonavir and efavirenz-based therapy. Placental blood smear
identified a prevalence of 4% among women taking efavirenz and 3% among women taking the protease inhibitor. Prevalence was also similar using
PCR testing (efavirenz 10% vs lopinavir/ritonavir 7%) and histopathology
(efavirenz 29% vs lopinavir/ritonavir 38%).
Rates of adverse
birth outcomes were also comparable between the two regimens (efavirenz 28% vs
did not reduce the risk of malaria during or after pregnancy, or the prevalence
of asymptomatic malaria parasites.
[World Health Organization] guidelines recommending efavirenz-based combination ART for all HIV-infected
and breastfeeding women offer the potential of immense benefits in preservation
of women’s health and reducing transmission,” comment the investigators. “The
main conclusion of this study is that lopinavir/ritonavir did not have
sufficient direct antimalarial activity to translate into a clinically
meaningful benefit that would support utilizing it in place of efavirenz in
highly malaria endemic regions.”